Slide 1

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 2

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 3

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 4

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 5

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 6

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 7

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 8

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 9

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 10

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 11

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 12

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 13

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 14

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 15

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 16

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 17

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 18

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 19

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 20

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 21

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 22

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 23

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 24

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 25

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 26

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 27

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 28

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 29

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 30

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 31

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 32

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 33

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 34

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 35

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 36

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 37

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 38

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 39

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 40

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 41

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 42

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 43

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 44

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 45

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 46

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 47

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 48

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 49

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 50

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 51

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 52

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 53

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 54

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 55

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 56

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 57

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 58

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 59

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 60

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione


Slide 61

PAD
e
MALATTIA CARDIOVASCOLARE

Incontri Pitagorici di Cardiologia 2010
1-2 Ottobre - Crotone
Agostino Talerico
Unità Operativa Semplice di Angiologia
Ospedale San Giovanni di Dio - Crotone

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Aterotrombosi
• Improvvisa e imprevedibile erosione o rottura
di placca aterosclerotica con attivazione
piastrinica e formazione di trombo

rottura di placca

erosione di placca

Evento comune che provoca infarto
miocardico, ictus ischemico, e morte
vascolare

Aterotrombosi : concomitanza
Elevata prevalenza di malattia polidistrettuale
Il Registro di REACH
Tra i pazienti sintomatici:
- 8,4% CVD e CAD
- 4,7% CAD e PAD
- 1,2% CVD e PAD
- 1,6% CVD,CAD e PAD
PREVALENZA
GLOBALE:

Malattia
Cerebrovascolare

8.4%
N=16901

N=38006

1.6%
1.2%

15,9%

Malattia
Coronarica

4,7%
11.8%

PAD
N=11770
Arteriopatia Periferica

Bhatt DL et al JAMA 2006:295:180-189

Rischio di un secondo evento vascolare

Aumento del rischio vs. popolazione generale
Evento iniziale

Infarto miocardico

Ictus

Infarto miocardico

5–7 volte1

3–4 volte2

2–3 volte2

9 volte3
2–3 volte3

(inclusa la morte)
Ictus

(inclusa angina e
morte improvvisa*)

Arteriopatia obliterante
periferica

(incluso TIA)

(incluso TIA)

4 volte4

(inclusi solo IM fatale e
altre morti CV†)

* morte documentata entro 1 ora e attribuita a cardiopatia ischemica
† inclusi solo IM fatali e altre morti cardiache; non sono inclusi gli IM non fatali
1.
2.
3.
4.

Adult Treatment Panel II. Circulation 1994; 89: 1333–1363.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
5

ATS and Life Expectancy

Analysis of data from the Framingham Heart Study
Peeters A et al: Eur Heart J 2002 23:458-466

6

World ‘s top 10 causes of death 2004

Deaths in millions

% of deaths

Coronary heart disease
Stroke and other cerebrovascular diseases

7.20
5.71

12.2
9.7

Lower respiratory infections

4.18

7.1

Chronic obstructive pulmonary disease

3.02

5.1

Diarrhoeal diseases

2.16

3.7

HIV/AIDS

2.04

3.5

1.46

2.5

Trachea, bronchus, lung cancers

1.32

2.3

Road traffic accidents

1.27

2.2

Prematurity and low birth weight

1.18

2.0

Poi ci sono Tuberculosis
gli anziani che non camminano

Risk Factors of ATS

Male gender

-3 -2 -1

0

1

2

3

4

5

6

7

ODDS ratios for
risk factors for
developing
and
progression
of local PAD
in the legs

Age (per 10 years)
Diabetes
Smoking
Hypertension
Hypercholesterol.
Fibrinogen
Alcohol
Hyperhomocystein.

Protective

Harmful
Angiology Care Unit - Padua - Italy - 2001

8

Prevalence of Peripheral Arterial Disease

PAD affects 12 % of the adult population
- 20% of population aged > 70

1,2

PAD is associated with 6-fold increase in CV mortality 3
- underrecognised and untreated 4
PAD requires simple, inexpensive, non invasive measurement
for appropriate diagnosis, risk assessment and
screening
PAD Patients need aggressive risk-factor modification and
pharmacological treatment

1
2
3
4

Nicolaides AN Symposium Nov 1997
Hiatt WR Circulation 1995 91:1472-1479
Criqui MH NEJM 1992 326:381-386
Hirsch AT JAMA 2001 286:1317-1324
9

PAD CLASSIFICATIONS
FONTAINE Helv Chir Acta 1954; 21: 499-533
J Vasc Surg 1997;26 (Suppl. 3):517-38 RUTHERFORD

STAGE

ASYMPTOMATIC

1ST

2ND

2ND

CLINICAL

A

B

3RD

4TH

MILD
CLAUDICATION

MODERATE
OR
SEVERE
CLAUDICATION

ISCHAEMIC
REST PAIN

ULCERATION
OR
GANGRENE

SIGNS &
SYMPTOMS
FORTUITOUS
DISCOVERY OF
AORTIC & ILIAC
CALCIFICATIONS

PATHOPHYSIOLOGY

ATS PLAQUE
RISK PLAQUE
INFLAMMATION

ABSOLUTE
CLAUDICATION
DISTANCE > 200 MT
RECOVERY T. < 2 MIN

DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 200 M
RECOVERY TIME
> 2 MIN

HIGHER DISCREPANCY
OXYGEN REQUEST
ARTERIAL SUPPLY

ACD < 100 M
RECOVERY TIME
> 2 MIN
REST
PAIN
NECROSIS
GANGRENE

HIGHEST
DISCREPANCY
AND ACIDOSIS
SKIN HYPOXIA
ACIDOSIS
SEVERE SKIN
HYPOXIA
ACIDOSIS
INFECTIONS

CLINICAL

ASYMPTOMATIC

MILD

GRADE
CATEGORY

0 / 0

I / 1

CLAUDICATION
MODERATE

I / 2

CLAUDICATION
SEVERE
CLAUDICATION

I / 3

ISCHAEMIC
REST PAIN

II / 4

MINOR
TISSUE
LOSS

III / 5

MAJOR
TISSUE LOSS

III / 6
10

– Presentazione clinica della PAD
• Asintomatica ( aterosclerosi occulta )

• Sintomatica ( claudicatio intermittens )

• CLI ( Ischemia critica cronica )

Ischemia Cronica Critica (CLI)
- Dolori a riposo (notturni) da più di 15 giorni
- Necessità di analgesici
- Lesioni trofiche cutanee
European Working Group CLI Circulation 1991

OUTCOME (1 anno) %
NON RIVASCOL.
40
MORTE
20
AMPUT.MAGGIORE
20
SALVATAGGIO D’ARTO 0

RIVASCOL.
60
10
15
35

Dormandy J, Murray GD: Eur J Vasc Surg 1991 5 131-3

12

The Diagnosis of CLI matches many different clinical pictures,
each Patient need for an own pathophysiological assessment

13

Definitions of Intermittent Claudication

Mild Claudication
leg’s pain that occurs during walking > 200 m.
and goes away after resting
leg’s pain after climbing more than two flights of stairs

Moderate Claudication
leg’s pain that occurs during walking < 200 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than two flights of stairs
Severe Claudication
leg’s pain that occurs during walking < 100 m.
and goes away after resting, with recovery time > 2 min.
leg’s pain after climbing less than one flight of stairs
14

Prevalenza di PAD Asintomatica(ABI patologico)e di
Claudicatio Intermittens nella popolazione generale

12 %

12

PAD asintomatica

10

intermittent
claudication

8
6
4
2
0

2%

– Raccomandazioni TASC 2 per lo sreening dei
pazienti con PAD asintomatica
• Soggetti con una storia, o visita medica , suggestiva di
PAD( B )

• Pazienti a rischio PAD ( tra 50 e 69 anni con storia di
diabete o fumo, o chiunque abbia più di 70 anni )
(A)
• Pazienti con un Framingham risk score di 10% -20% in
10 anni ( B )
• Concomitanza di malattia carotidea cardiaca o renale

Sig.ra Maria
• Donna
• 60 anni
• Madre deceduta per ictus
• Padre vivente; cardiopatia ischemica
• Impiegata
• Sposta; due figli
• Palestra 2 volte a settimana
• Fuma 15 sigtte/die dall’età di 17 anni
• Non diabetica
• Colesterolo 230 mg/dl
• LDL 110 mg/dl
• Trigliceridi 201 mg/dl
• BMI 28
• ECG negativo
• PAO 140/80 mmHg

Carta italiana del rischio Cardiovascolare
Istituto Superiore di Sanità

The new European Risk Chart based on SCORE data.
Adapted from Conroy et al, Eur Heart J. 2003;24:987-1003.
European Society of Cardiology.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl

E’ sufficiente ??

Diet therapy if LDL > 160 mg/dl
0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Sottoporre la paziente ad
indagini per
Aterosclerosi occulta,
sarebbe una buona idea ????

Subclinical atherosclerosis tests

ABI - Definition

RATIO
Ankle systolic pressure
Brachial systolic pressure

Equipment for measurement of
Ankle/Brachial Index (ABI)

Doppler CW
Probe 8 mHz

Sphygmomanometer

The measurement of ABI

The measurement of ABI

The measurement of ABI

Calculation of Ankle/Brachial Index
Right ABI
Higher of the rigth ankle systolic pressure
(dorsalis pedis or posterior tibial)
Higher brachial systolic pressure
(Left or right arm)

Left ABI
Higher of the left ankle systolic pressure
(dorsalis pedis or posterior tibial )
Higher brachial systolic pressure
(Left or right arm)

Sig. ra Maria
ABI =0.83

ABI =0.90-1.30
NORMAL VALUE

ABI < 0.90
=
Haemodynamically
significant arterial stenosis
=
Peripheral Arterial Disease

As the 85% of PAD is
determined by
ATHEROSCLEROSIS
ABI < 0.90
=
ATHEROSCLEROSIS

Sig. ra Maria
Rischio Cuore ISS <10%

+
ABI = 0.83
=
Asymptomatic PAD
=
Subclinical
ATHEROSCLEROSIS

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories

(1) Established CHD and CHD risk equivalents
(2) Multiple risk factors(2+)
(3) Zero to one risk factor

NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
CHD risk equivalents include
• Non coronary forms of clinical atherosclerotic disease
• Diabetes
• Multiple (2+) risk factors with 10-year risk for CHD >20%

All persons with CHD or CHD risk equivalents can be called
high risk
NCEP Report Adult Treatment Panel
Scott M. Grundy
Circulation. 2004;110:227-239.

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

ATP III
Risk categories
RISK CATEGORY

LEVELS

Established CHD
and CHD
risk equivalents

Multiple
(2+) risk factors

LDL-C goal

TREATMENT

< 100 mg/dL

Diet therapy + Drugs If LDL >
100 mg/dl

> 20%

< 100 mg/dL

Diet therapy + Drugs if LDL >
100 mg/dl

10% to 20%

< 130 mg/dL

Diet therapy + Drugs if LDL >
130 mg/dl

< 10%:

< 160 mg/dL

Diet therapy + Drugs if LDL >
160 mg/dl
Diet therapy if LDL > 160 mg/dl

0 to 1 risk factor

< 10%

< 160 mg/dL

Drugs if LDL 160 to 189 mg/dL if
severe risk or LDL > 190 mg/dL

Ankle Brachial Index Combined
With Framingham Risk Score to Predict
Cardiovascular Events and Mortality
A Meta-analysis

JAMA, 2008

Algorithm for use of the ABI in the assessment of
systemic risk in the population

Secondary prevention:

Primary prevention:

Antiplatelet therapy
LDL <2.59 mmol/L (<100 mg/dL) (<1.81
mmol/L [<70 mg/dL] in high risk); blood
pressure <140/90 mmHg and <130/80
mmHg in diabetes/renal insufficiency.
In diabetes, HbA1c <7.0%.

No antiplatelet therapy
LDL <3.37 mmol/L (<130 mg/dL) except in
diabetes where the LDL goal is <2.59 mmol/L
(<100 mg/dL) even in the absence of CVD
(cardiovascular disease); appropriate blood
pressure (<140/90 mmHg and <130/80 mmHg
in diabetes/renal insufficiency)

L. Norgren et al TASC 2007

is The ABI a BIOmarker of Cardiovascular Risk ?

SENSIBILITA’ 95%
SPECIFICITA’ 100%
Nel rivelare una malattia
angiograficamente
significativa

Fowkes: Int J Epidemiol 1988

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?

All-Cause Mortality by ABI Category

0

Anand V. Arterioscler Thromb Vasc Biol 2005

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Anamnesis and
Vascular Visit
Doctor’s
Request for vascular
Investigatinos (all types)

Specific Vascular
Investigations

483

ATS in different sites
from ones of Doctor's R.

108

22.5%

Cervical Bruits

52/108

48%

carotid stenosis > 50%
27/52

50%
Abdominal Pulsating
Mass

30/108

28%

AAA > 30 mm 
14/30

47%
Peripheral Artelial Pulseless

26/108

24%

ABI < 0.90
22/26

85%

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Inadherence to Diagnostic Guidelines
70
60

62%
45%

50

35%

40
30
20
10
0
No SAA ECD
(219/483)

No Aorta ECD
(169/483)

No ABI Meas.
(201/483)

is The ABI a BIOmarker of Cardiovascular Risk ?
Marzolo M, Verlato F, et al: Int Angiol. 2008 27(5):426-32

Patients not Adequately Treated

60

55%

50

45,7%

40
30
16,6%

Obese

5,4%

Overweight

BP>180/100

0

Hyperchol

10

13,9%

Smokers

10,6%

Smokers >
20

20

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?

Resnick HE et al. Circulation 2004

Fate of the
Claudicant Patient
(5 years)

75 stabilise
or improve
mild-moderate
claudication

300 people with
asymptomatic
PAD

100 pts Int. Cl.
presenting
to doctor

100 pts Int. Cl.
do not present
to doctor

Local
Outcome
Systemic Outcome
25
deteriorate

7
C.L.I.

18 severe
claudication

3
amputation
4 limb
salvage

5-10 non-fatal
CV events
in 5 years

6 require
intervention

12 stabilise
severe claudic

55-60 alive
without new
CV event

30 will die
within 5 years
16 cardiac
4 cerebral
3 other vascular
7 non-vascular

49

Quanto è frequente il riscontro di aterosclerosi asintomatica
inteso come ABI patologico ( <=0.9 )nella popolazione
ritenuta a rischio medio – basso ?
• Studio GET ABI ( Germania ): 6.880 soggetti consecutivi
non selezionati che si riferivano all’ambulatorio del
medico di famiglia età ≥65 anni .
12.2 %
• Studio YPSILON( Francia ): 2077 soggetti di età media
67 anni con 2 o più fattori di rischio ma senza malattia
aterosclerotica conclamata
10.4 %
• StudioPANDORA(Italia,Grecia,Francia,Svizzera,Belgio,
Olanda)10500 soggetti ( donne età ≥55, uomini ≥45 ed
almeno 1 fattore di rischio aggiuntivo ( escluso diabete )
17.8 %

Studio getABI
- Studio Osservazionale :344 Medici di Famiglia hanno
selezionato 6.880 pz. a prescindere dal motivo per
vedere il medico nell’arco di 1 settimana
prespecificata ( ottobre 2001 )
Senza PAD 5329 ( 79% )
- 6.821
asintomatici 836 (12.3%)
Con PAD 1429 ( 21% )
sintomatici 593 (8.7%)

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Diehm Circulation 2009

is The ABI a BIOmarker of Cardiovascular Risk ?
Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic
Peripheral Artery Disease : GETABI Study

Conclusioni
Pazienti con PAD( sintomatica o asintomatica )
Hanno un sostanziale aumento di rischio di
Ictus ( apoploettico , ischemico, fatale ).
I pazienti anziani nel setting di assistenza
primaria devono essere sottoposti a
screening per PAD per consentire un
trattamento rigoroso dei fattori di rischio
modificabili per ridurre il rischio di ictus
ischemico e di altri eventi vascolari

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Quanto è frequente il riscontro di un ABI <= 0.9
nel paziente cerebrovascolare?
• Studio Busch :

31%

Stroke 2009

• Studio Weimar:

40.6%

J Neurol Neurosurg Psychiatry 2008

• Studio Pathos

33.9%

JTH

• Studio Agatha
Eur Heart

26.1%

Lo studio Pathos
Prevalenza di ABI<0,9(rilevato nel corso dell’ospedalizzazione per
l’evento indice)nelle diverse categorie di pazienti

CAD: n=1011
CVD: n=761
Totale: n=1772

33,9
35
30

30,2

27,5

25
20
15
10
5
0
SCA

ictus/TIA

TOTALE

Lo Studio Pathos
Percentuale di pazienti con eventi validati durante
il follow-up (periodo mediano di 372 giorni)
p = 0,0003
OR 1,96 (IC 95% 1,36-2,81

12

OR 2,14 (IC 95% 1,31-3,50)

10,8

10

7

8
6

5,9

5,9
3,7

4

2,9

2
0
Endpoint
primario

Morte
vascolare

Morte
totale

ABI anomalo
ABI normale

Conclusioni
Un Abi anormale potrebbe essere trovato in
un terzo dei pazienti che hanno avuto sindromi
coronariche acute o eventi cerebrovascolari ,
identifica una popolazione ad alto rischio di
eventi cerebrovascolari fatali e non fatali
entro un anno che dovrebbero essere
strettamente monitorati e dovrebbero
diventare bersaglio di un intervento
terapeutico più aggressivo

ABI biomarker affidabile di rischio
cardiovascolare
-Tradizionalmente usato come strumento diagnostico
e prognostico per la gestione della arteriopatia
periferica ( PAD )
- Molti studi precedenti hanno dimostrato il suo
valore come predittore di rischio C.V. Nel lungo
periodo ( rischio primario )
- Studi più recenti hanno dimostrato che in paz CHD
o equivalenti un ABI anomalo ( sintomatico o
asintimatico )è associato ad un esito sfavorevole dopo
un periodo di 4-5 anni .
- Lo studio Pathos ha dimostrato che una PAD
sintomatica o asintomatica è fattore prognostico
sfavorevole nel breve periodo .

Grazie per l’attenzione