Transcript HTN & CHD

ΥΠΕΡΤΑΣΗ
ΚΑΙ
ΣΤΕΦΑΝΙΑΙΑ ΝΟΣΟΣ
Athanasios J. Manolis MD
Progression of Cardiovascular Disease
Focus on LVH
Smoking
Dyslipidemia
Diabetes
MI
Systolic
Dysfunction
CHF
Hypertension
Obesity
Diabetes
LVH
LV
Remodeling
Years
(Adapted from Levy D. J Am Coll Cardiol 1993)
Death
Diastolic
Dysfunction
Subclinical
LV
Dysfunction
Possible
pathway
of progression
Overt
Failure
months
Cardiovascular disease:
the leading cause of death worldwide
East Mediterranean area
Europe
IHD
IHD
25.5
13.7
Stroke
13.6
Pneumonia
9.1
West Pacific
Stroke
14.3
COPD
12.0
Lung cancer
4.2
Diarrhoea
7.4
IHD
Pneumonia
3.6
Perinatal death
7.3
Pneumonia
4.0
Suicide
3.8
COPD
5.3
Stroke
2.7
11.1
Japan
Stroke
America
Africa
IHD
17.9
Stroke
Pneumonia
Lung cancer
Traffic accident
10.3
4.2
19.0
10.0
Malaria
3.2
Diarrhoea
3.1
Perinatal death
Pneumonia
8.6
IHD
Stomach
cancer
Lung cancer
7.9
5.4
5.4
South East Asia
HIV infection
Pneumonia
15.2
8.2
7.6
5.5
IHD
13.8
Pneumonia
9.3
Diarrhoea
6.6
Stroke
6.5
Perinatal death
6.0
Values are percentages of death rate.
IHD = ischaemic heart disease; COPD = chronic obstructive pulmonary disease; HIV = human
immunodeficiency virus;
WHO The World Heart Report 1999, Nikkei Medical 1999, Japan Welfare Ministry 1997
CVD = cardiovascular disease
Lifestyles and characteristics associated with increased
risk of future coronary heart disease
Lifestyles
Biochemical or physiological
characteristics (modifiable)
Personal
characteristics
(non-modifiable)
Diet high in
saturated fat,
cholesterol and
calories
Tobacco smoking
Elevated plasma total cholesterol
(LDL Cholesterol)
Age
Elevated blood pressure
Gender
Excess alcohol
consumption
Low plasma HDL cholesterol
Family history of CVD
or other atherosclerotic
vascular disease at
early age men <55
years, in women <65
years)
Physical inactivity
Hyperglycaemia / diabetes
Personal history of CVD
or other atherosclerotic
vascular disease
Obesity
Thrombogenic factors (e.g
fibrinogen)
“New” cardiovascular risk factors
•
•
•
•
•
Left ventricular hypertrophy (LVH)
Hyperhomocysteinaemia
Lipoprotein (a) excess
Hypertriglyceridaemia
Increased thrombogenicity and decreased fibrinolytic
activity
• Oxidative stress
• Infectious agents
• Markers of inflammation, such as C-reactive protein
Hypertension Syndrome—It’s More Than
Just Blood Pressure
Obesity
Decreased
Arterial
Compliance
Abnormal
Glucose
Metabolism
Abnormal Lipid
Metabolism
Accelerated
Atherogenesis
Endothelial
Dysfunction
Hypertension
LV Hypertrophy
and Dysfunction
Abnormal
Insulin
Metabolism
Neurohormonal
Dysfunction
Renal-Function
Changes
Blood-Clotting
Mechanism
Changes
Kannel WB. JAMA. 1996;275:1571-1576. Weber MA et al. J Hum Hypertens. 1991;5:417-423. Dzau
VJ et al. J Cardiovasc Pharmacol. 1993;21(suppl 1):S1-S5.
ESH: Factors influencing prognosis
Risk factors for cardiovascular
disease used for stratification
 Levels of systolic & diastolic BP
 Men > 55 years
 Women > 65 years
 Smoking
 Dyslipidaemia
(total cholesterol >6.5 mmol/l, >250
mg/dl *, or LDL-cholesterol > 4.0
mmol/l, >155 mg/dl*, or HDLcholesterol M < 1.0, W< 1.2 mmol/l,
M<40,W <48 mg/dl)
 Family history of premature
cardiovascular disease
(at age < 55 years M, < 65 years W)
 Abdominal obesity
(abdominal circumference M  102
cm, W  88 cm)
 C-reactive protein  1 mg/dl
Target organ
damage (TOD)
 Left ventricular
hypertrophy
(electrocardiogram: Sokolow–
Lyons > 38 mm; Cornell >
2440 mm* ms; echocardiogram:LVMI M  125,
W  110 g/m2)
 Ultrasound evidence of
arterial wall thickening
(carotid IMT  0.9 mm) or
atherosclerotic plaque
 Slight increase in serum
creatinine
(M 115–133, W 107– 124
μmol/l; M 1.3–1.5, W 1.2–1.4
mg/dl)
 Microalbuminuria
(30–300 mg/24 h; albumin–
creatinine ratio M 22, W 31
mg/g;M 2.5, W 3.5
mg/mmol)
Diabetes
mellitus
Associated clinical
conditions (ACC)
 Fasting plasma
glucose
7.0 mmol/l
 Cerebrovascular disease:
ischaemic stroke; cerebral
haemorrhage; transient
ischaemic attack
 Heart disease:
myocardial infarction;
angina; coronary
revascularization;
congestive heart failure
 Renal disease:
diabetic nephropathy;
renal impairment
(126 mg/dl)
 Postprandial
plasma glucose
> 11.0 mmol/l
(198 mg/dl)
(serum creatinine M >133, W
>124 μmol/l; M >1.5, W > 1.4
mg/dl) proteinuria (>300
mg/24 h)
 Peripheral vascular
disease
 Advanced retinopathy:
haemorrhages or
exudates, papilloedema
M, men; W, women; LDL, low-density lipoprotein; HDL, high-density lipoprotein; LVMI, left ventricular mass index; IMT, intima-media
thickness. Lower levels of total and LDL-cholesterol are known to delineate increased risk, but they were not used in the stratification
• Vascular disease—and CAD in particular—
is the leading cause of death in the US and
other Western nations
• By 2020, cardiovascular disease will become
the most common cause of death worldwide
• Due to the high initial mortality of vascular
disease, the target of clinical practice must be
aggressive risk factor management
Coronary Artery Disease (CAD):
The Diagnosis Often Comes Too Late
Atherosclerosis Begins in Childhood
(Adapted from Berenson et al.)
Berenson GS et al, N Engl J Med, 1998.
Most Myocardial Infarctions Are Caused
by Low-Grade Stenoses
Pooled data from 4 studies: Ambrose et al, 1988; Little et al, 1988; Nobuyoshi et al, 1991; and Giroud et al, 1992.
(Adapted from Falk et al.)
Falk E et al, Circulation, 1995.
CAD: Not Just a Lipid Disease
• Half of all MIs occur in normolipidemic patients
• Smoking
Accounts for 200,000 cardiovascular deaths annually
• Diabetes
Affects 16 million Americans—and is growing
• Hypertension
Confers as much risk for MI as smoking or dyslipidemia
– Systolic hypertension is an even greater indicator of
CAD risk than diastolic hypertension
Braunwald E, N Engl J Med, 1997; Grundy SM et al, Circulation, 1998; The Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure and the National High Blood Pressure Education Program Coordinating Committee, Arch Intern Med, 1997.
Total Cholesterol Distribution:
CHD vs Non-CHD Population
Framingham Heart Study—26-Year Follow-up
No CHD
35% of CHD
Occurs in
People with
TC<200
mg/dL
CHD
150
200
250
300
Total Cholesterol (mg/dL)
Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9.
1996 Reprinted with permission from Elsevier Science.
Small Increases in Cholesterol Lead to Dramatic
Increases in CAD Death
(Adapted from Neaton et al.)
Neaton JD et al, Arch Intern Med, 1992.
Impact of High-Normal BP on CV Disease
Risk in Men
Cumulative Incidence (%)
16
14
12
Highnormal
10
Normal
8
6
Optimal
4
2
0
0
2
4
6
Time (y)
8
10
12
Optimal: <120/80 mm Hg; normal: 120-129/80-84 mm Hg; high-normal: 130-139/85-89 mm Hg.
Vasan RS. N Engl J Med. 2001;345:1291-1297.
Metabolic Syndrome:
NCEP ATP III Criteria
 Three or more of the following:
– Abdominal obesity
waist: male >102 cm, female >88 cm
– Triglycerides 150 mg/dL
– HDL cholesterol
Male <40 mg/dL, female <50 mg/dL
– SBP 130 mm Hg or DBP  85 mm Hg
– Fasting glucose 110 mg/dL (IFG)
NCEP=National Cholesterol Education Program.
ATP III=Third Report of NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
Distribution of the components of the metabolic
syndrome in the population of the ATTICA Study
Males
Females
Waist circumference > 102 cm ♂ or > 88 cm ♀
31.8%
29.7%
Triglycerides Level > 150 mg/dL
28.4%
12.7%*
HDL – C Level < 40 mg/dL ♂ or < 50 mg/dL ♀
37.6%
37.4%
Arterial Blood Pressure > 130/85 mm Hg
43.7%
34.9%*
Fasting Blood Glucose > 110 mg/dL
14.2%
7.7%*
* p < 0.05
Panagiotakos D. et al. Am Heart J 2004
Impact of Lifestyle Habits on the Prevalence of the MS among
Greek Adults from the ATTICA Study
Levels of anthropogenic, inflammation and coagulation markers in pts with MS
Participants without MS
Apo A1 (mg/dL)
ApoB (mg/dL0
CRP
LDL-C (mg/dL)
WBC (counts)
Homocysteine (nmol/L)
Fibrinogen (mg/dL)
Serum amyloid A (mg/dL)
Lipoprotein-a (mg/dL)
Oxidized LDL-C (mg/dL)
158±26
105±41
2.16±4.36
123±37
6.61±1.8
12.2±5.3
315±149
5±8
19.8±28.9
63.2±30
Participants with MS
146±71
123±28
3.65±4.7
132±37
7.14±1.8
13.6±6.9
338±73
5.95±7.5
17.65±22
63.7±32
p<
<.001
<.001
<.001
<. 001
<.001
<.001
<.003
<.058
<.082
<.883
Panagiotakos D. et al. Am Heart J 2004
Atherosclerosis:
a multifactorial disease
• What is the current understanding of the
atherosclerotic process?
• What is the role of endothelial
dysfunction in atherosclerosis and
hypertension?
• How do dyslipidemia and hypertension
interact to exacerbate disease?
Different stages of atherosclerotic plaque
development
• What is the current understanding of the
atherosclerotic process?
• What is the role of endothelial
dysfunction in atherosclerosis and
hypertension?
• How do dyslipidemia and hypertension
interact to exacerbate disease?
CVD Risk Factors and Endothelial
Dysfunction
Dyslipidemia
Diabetes
Hypertension
Smoking
Endothelium
Dysfunction
Vasoconstriction
Cell adhesion
and/or infiltration
Dzau VJ. J Cardiovasc Pharmacol. 1990;15(Suppl 5):S59-S64.
Proliferation Lipid accumulation
and clearance
HTN, hemodynamic factor and atheroclerosis
HTN creates areas of low sear stress within arteries
• What is the current understanding of the
atherosclerotic process?
• What is the role of endothelial dysfunction
in atherosclerosis and hypertension?
• How do dyslipidemia and hypertension
interact to exacerbate disease?
CAD Risk Is Incremental
(Adapted from Neaton et al.)
Neaton JD et al, Arch Intern Med, 1992.
Interaction of Hypertension and
Dyslipidemia and Atherosclerotic Risk
Hypertension
Dyslipidemia
Endothelial dysfunction
 NO Synthesis
Inflammation
 Endothelin
↑ Vasoconstriction
↑ Leukocyte
adhesion
↑ Endothelial
permeability
↑ Foam cell
formation
↑ T cell
activation
Vasoconstriction
↑ Thrombosis
↑ Superoxide
production
Adapted from Mason RP. Cerebrovasc Dis. 2003;16(Suppl 3):11-17.
Calcium
mobilization
Role of Angiotensin II in the Progression of
Atherosclerosis
Angiotensin II
Activation of NADH
oxidase in endothelial cell Oxidized
 O2 generation
LDL
O2
O2
 LOX-1 receptors
 LDL oxidation
and uptake by
macrophages
 Uptake of oxidized LDL
 NO
Interference with endotheliumdependent vasodilation
Endothelial cell injury
NADH = nicotinamide adenine dinucleotide.
Vaughan DE. Circulation. 2000;101:1496-1497.
Accumulation
of lipids
in plaques
Formation
of foam cells
Vulnerable plaque
Key role of the macrophage in vascular wall inflammation
Thrombosis of a Disrupted Atheroma, the Cause of
Most Acute Coronary Syndromes, Results from:
Illustration courtesy of Michael J. Davies, M.D.

Weakening of
the fibrous cap

Thrombogenicity of
the lipid core
Plaque Rupture with Thrombosis
Thrombus
1 mm
Illustration courtesy of Frederick J. Schoen, M.D., Ph.D.
Fibrous cap
Lipid core
CVD has the highest economic impact of all
diseases (15% of total healthcare costs)
Percentage of total
healthcare costs:
Canada 1993
Musculoskeletal
13.8%
Injuries 11.1%
Cardiovascular
disease (CVD) 15.2%
Cancer 10.1%
Respiratory disease
9.4%
Nervous system
disorders 7.4%
Mental disorders
6.0%
Digestive disorders
4.8%
Other 21.3%
Diabetes 0.9%
Source: www.hc-sc.gc.ca/hpb/lcdc/publicat/burden/burd1_e.html
How to reduce the risk of plaque rupture
Implications for Treatment
Dyslipidemia
Statins
Synergistic
increase in
CV risk
Synergistic
reductions in
CV risk?
Hypertension
Antihypertensives
Lifestyle Modification
Modification
Weight reduction
Approximate SBP reduction
(range)
5–20 mmHg/10 kg weight loss
Adopt DASH eating plan
8–14 mmHg
Dietary sodium reduction
2–8 mmHg
Physical activity
4–9 mmHg
Moderation of alcohol
consumption
2–4 mmHg
Mechanism by Which Diet Potentially
Influences Risk of CHD
Intermediary Biological Mechanism
Lipid Levels
Low-Density Lipoprotein Cholesterol
High-Density Lipoprotein Cholesterol
Triglycerides
Lipoprotein(a)
Diet
Blood Pressure
Thrombolic Tendency
Cardiac Rhythm
Endothelial Function
Systemic Inflammation
Insulin Sensitivity
Oxidative Stress
Homocysteine Level
Risk of
Coronary
Heart
Disease
Food Pyramid Reflecting the Traditional Healthy
Mediterranean Diet
Adherence to a Mediterranean Diet and Survival in Greek
Population
Trichopoulou A. et al. N Engl J Med 2003
Mediterranean Diet Score, Other Baseline Characteristics and Mortality
among 22.043 study Participants
Variable
MD Score 0-3
(N=6848)
MD Score 4-5
(N=9488)
MD Score 6-9
(N=5707)
Multivariate
HR for Death
no of Deaths
no of Deaths
no of Deaths
Sex: Male
Female
74
45
61
34
44
17
1.00
0.39
Age: < 55
55-64
> 65
16
23
80
13
20
62
17
12
32
1.00
3.30
10.14
BMI: < 28
> 28
55
64
41
54
26
35
1.00
1.05
W/H ratio: < 0.87
> 0.87
37
82
22
73
11
50
1.00
1.05
Physical Activity:
< 35 met - hr/day
> 35 met - hr/day
94
25
67
28
35
26
1.00
0.72
Relative risk of outcome event
1.50
1.50
1.50
Stroke
Major CVD
CHD
1.25
1.25
1.25
1.00
1.00
1.00
0.75
0.75
0.75
0.50
0.50
0.50
0.25
0.25
0.25
-10 -8
-6
-4
-2
0
2
4
-10 -8
1.50
-6
-4
-2
0
2
4
-10 -8
-6
-4
-2
1.50
CVD death
Total mortality
1.25
1.25
1.00
1.00
0.75
0.75
0.50
0.50
0.25
0.25
-10 -8
-6
-4
-2
0
2
4
-10 -8
-6
-4
-2
0
SBP difference between randomized groups (mmHg)
2
4
0
2
4
Odds Ratio (experimental/reference)
Odds Ratio for CV Events and Systolic BP
Difference: Recent and Older Trials
1.50
Recent trials
Older trials placebo
1.25
Older trials active
P<.0001
1.00
0.75
0.50
0.25
-5
0
5
10
15
20
25
Difference (reference minus experimental)
in Systolic BP (mm Hg)
Recent
Older
AASK L vs H
ABCD/NT L vs H
ALLHAT/Aml
ALLHAT/Lis
ALLHAT/Lis 65
ALLHAT/Lis Blacks
ANBP2
CONVINCE
DIABHYCAR
ELSA
IDNT2
LIFE/ALL
LIFE/DM
NICOLE
PREVENT
SCOPE
ALLHAT/Dox
ATMH
EWPHE
HEP
HOPE
HOT
HOT M vs H
INSIGHT
MIDAS/NICS/VHAS
L vs H
MRC
MRC2
PART2/SCAT
PATS
PROGRESS/Per
PROGRESSION/Com
RCT70-80
RENAAL
SHEP
STONE
STOP 1
STOP2/CCBs
STOP2/ACEIs
Syst-China
Syst-Eur
UKPDS C vs A
UKPDS L vs H
Staessen et al. J Hypertens. 2003;21:1055-1076.
Superior Effect of New vs Conventional Drugs on Markers of TOD
(Intermediate End-Points)
LV hypertrophy
ACEI / CA / ARB
Carotid artery IMT /
CA / ACEI
Atherosclerosis
ACEI / ARB / CA
Arteriolar remodelling
ACEI / ARB
Urinary protein excretion
CA / ACEI (?) / ARB
Endothelial dysfunction
(?)
Arterial stiffening
?
Mild renal damage
CA
CA coronary content
CA
Where ACE Inhibitors Work
Sudden
death
Angina
Ventricular
arrhythmias
Hypertension
Coronary
artery
disease
Diabetes
Myocardial
LV
infarction dysfunction
Hyperlipidemia
Hypertrophic
cardiomyopathy
Heart
failure
Atrial
Cardiac
Pump
fibrillation
rupture
failure
Mechanical death
SAVE
AIRE
Radionuclide
EF  40%
TRACE
Clinical and/or
radiographic
signs of HF
Echocardiographic
EF  35%
All-Cause Mortality
0.4
Placebo
0.35
0.3
ACE-I
0.25
Probability
of Event 0.2
0.15
Placebo: 866/2971 (29.1%)
0.1
ACE-I: 702/2995 (23.4%)
0.05
Years
ACE-I
Placebo
0
OR: 0.74 (0.66–0.83)
0
2995
2971
1
2
2250
2184
1617
1521
Flather MD et al. Lancet. 2000;355:1575-1581.
4
3
892
853
223
138
SAVE
AIRE
Radionuclide
EF  40%
TRACE
Clinical and/or
radiographic
signs of HF
Echocardiographic
EF  35%
Death and Major CV Events
(0.67 – 0.83)
ACE-I (n = 2995)
40
0.75*
Placebo (n = 2971)
30
Events
(%)
0.73*
20
(0.63 – 0.85)
0.80*
(0.69 – 0.95)
10
n=
355
n=
460
n=
324
n=
391
n=
1049
n=
1244
0
Readmission
for HF
*Odds ratio (95% CI).
Flather MD et al. Lancet. 2000;355:1575-1581.
Reinfarction
Death/MI or
Readmission for HF
Repair of Coronary Arterioles After Treatment with
Perindopril in Hypertensive Heart Disease
% Morphological and Haemodynamic changes
before and after treatment.
7070
# 67%
# 54
%
*
p < 0,04
# p < 0.001
00
LVMI
* 12
%
CBF
CVR
CR
PCA
* 22%
# 33%
70-70
PCA: Periarteriolar collagen area
TIC: Total Interstitial Collagen
TIC
* 54%
Hypertension 2000
EUROPA: Aim of the study
To investigate whether long-term administration
of the ACE inhibitor perindopril, added to
standard therapy, leads to a reduction of
cardiovascular events in low risk patients with
documented coronary disease
EUROPA: Primary endpoint
% CV death, MI or cardiac arrest
14
Placebo
12
10
Perindopril
8
6
RRR: 20%
4
p = 0.0003
2
0
0
1
2
3
Placebo annual event rate: 2.4%
4
5 Years
EUROPA: Sub-groups analysis
Perindopril
better
Placebo
better
RRR (%)
Hypertension
18.6
No hypertension
19.9
Diabetes mellitus
18.9
No diabetes mellitus
19.0
Stroke/TIA
15.8
No stroke/TIA
19.9
0.5
1.0
2.0
VALIANT: Mortality by Treatment
0.3
Captopril
Valsartan
Valsartan + Captopril
0.25
0.2
Probability
0.15
of Event
0.1
0.05
Valsartan vs Captopril: HR = 1.00; P = 0.982
Valsartan + Captopril vs Captopril: HR = 0.98; P = 0.726
0
Months
0
Captopril 4909
Valsartan 4909
Valsartan + Cap 4885
6
12
18
24
30
36
4428
4464
4414
4241
4272
4265
4018
4007
3994
2635
2648
2648
1432
1437
1435
364
357
382
Pfeffer MA et al. N Engl J Med. 2003;349:1893-1906.
LIFE Study ISH Subgroup
Composite of CV Death, Stroke, and MI
Endpoint rate (%)
18 Unadjusted relative risk=29%; P=0.02
16
Adjusted relative risk reduction=25%; P=0.06
14
12
10
8
6
Atenolol
Losartan
4
2
0
0
6
12 18 24 30 36 42 48 54 60 66
Study monthCV=cardiovascular
MI=myocardial
infarction
LIFE Primary Composite Endpoint
in Subgroup: Patients without LVH* (n=662)
15
12,1
10
7,2
%
5
RR: 45%
p=0.019
0
Atenolol
n=330
* Cornell Voltage < 2400 and Sokolow-Lyon < 24
Losartan
n=332
Where b-Blockers Work
Sudden
death
Angina
Ventricular
arrhythmias
Hypertension
Coronary
artery
disease
Diabetes
Myocardial
LV
infarction dysfunction
Hyperlipidemia
Hypertrophic
cardiomyopathy
Heart
failure
Atrial
Cardiac
Pump
fibrillation
rupture
failure
Mechanical death
Beta-Blocker Trials Intervening
Within 24 Hours of an Acute MI
Study
# of
Patients
Treatment
Groups
Duration
of therapy
Effect on
Mortality
Effect on
Reinfarction
Göteborg
Study
1,395
Placebo
Metoprolol
3
months
MIAMI
Trial
5,778
Placebo
Metoprolol
3
months
NS
NS
ISIS-1
Trial
16,027
Placebo
Atenolol
1
week
 15%
(P < 0.04)
NS
TIMI IIB
Trial
1,434
Immediate vs
Late Metoprolol
12
months
NS
NS
 36% NS
(P = 0.03)
Beta-Blocker Trials Intervening
3 - 28 Days Following an Acute MI
Study
# of
Patients
Treatment
Groups
Average
Follow-up
Effect on Effect on
Mortality Reinfarction
Multicenter
International
3,038
Placebo
Practolol
12 - 36
months
 39%
(P < 0.01)
Norwegian
Trial
1,884
Placebo
Timolol
17
months
 39%
 28%
(P < 0.001) (P < 0.001)
BHAT
Trial
3,837
Placebo
Propanolol
25
months
 26%
(P < 0.005)
NS
Julian
Post-MI
1,458
Placebo
Sotalol
12
months
NS
 35%
(P = 0.07)
European
Infarction
1,741
Placebo
Oxprenolol
12
months
 risk
 risk
Lopressor
Intervention
3,395
Placebo
Metoprolol
12
months
NS
------
 23%
(P < 0.09)
CAPRICORN: All-Cause Mortality
Proportion Event-Free
1
23%  vs. placebo
P = 0.031
0.95
0.9
Carvedilol
0.85
0.8
Placebo
0.75
0.7
0
0.5
1
1.5
Years
2
2.5
Where Statins Work
Sudden
death
Angina
Ventricular
arrhythmias
Hypertension
Coronary
artery
disease
Diabetes
Myocardial
LV
infarction dysfunction
Hyperlipidemia
Hypertrophic
cardiomyopathy
Heart
failure
Atrial
Cardiac
Pump
fibrillation
rupture
failure
Mechanical death
Where Aspirin Works
Sudden
death
Angina
Ventricular
arrhythmias
Hypertension
Coronary
artery
disease
Diabetes
Myocardial
LV
infarction dysfunction
Hyperlipidemia
Hypertrophic
cardiomyopathy
Heart
failure
Atrial
Cardiac
Pump
fibrillation
rupture
failure
Mechanical death
Association of Hypertension with Other CAD Risk Factors:
Framingham Study
One
26%
One
27%
Two
25%
None
19%
Four or more
8%
Men
Three
22%
Two
24%
None
17%
Four or more
12%
Three
20%
Women
Kannel, Am J Hypertens 2000; 13: 3S-10S
A study of RF for first MI in 52 countries and over
27.000 subjects (INTER-HEART)
Risk Factors
OR
Apo B/A1
Smoking
Stress
Diabetes
Hypertension
Abdominal obesity
Lack of fruits and vegetables
Lack of daily exercise
3.25
2.87
2.67
2.37
1.91
1.62
0.70
0.86
8 factors
129.2
Mean age of MI was lower in men vs women by a median of 9 yrs
New DM in Antihypertensive Drugs Trials
CAPPP STOP-2ALLHAT HOPE
ACEI
vs
Conv
ACEI
vs
Conv
ACEI
vs
D
ACEI
vs
PL
STOP-2 INVESTINSIGHTALLHAT STOP-2
CA
vs
Conv
CA
vs
Conv
CA
vs
D
CA
vs
D
ACEI
vs
CA
LIFE SCOPE CHARM
ARB
vs
BB
ARB
vs
Conv
ARB
vs
PL
0
-2
-2
-4
-10
-16**
-14
-16
-20
-30
-20
-23
-30**
-25*
-34
-40
-40*
* T, 2 yrs; ** T, 4 yrs
-50
-25
-21
VALUE: Incidence of New-onset Diabetes
18
New-Onset Diabetes
(% of patients in
treatment group)
16
23% Risk Reduction
With Valsartan
P < 0.0001
14
12
10
8
6
16.4%
13.1%
4
2
0
Valsartan-based
Regimen
(n = 7649)
Amlodipine-based
Regimen
(n = 7596)
Julius S et al. Lancet. June 2004;363.
Patients on Combinations
No of antihypertensive drugs
UKPDS (<85 mmHg, DBP)
MDRD (92 mmHg, MAP)
HOT (<80 mmHg, DBP)
AASK (<92 mmHg, MAP)
RENAAL (<140/90 mmHg)
IDNT (135/85 mmHg)
1
2
3
Number of Antihypertensive Drugs
4
RENAAL=Reduction of Endpoints in NIDDM with the
Angiotensin II Antagonist Losartan;
IDNT=Irbesartan Diabetic Nephropathy Trial;
MAP=átlagos arteriális nyomás
UKPDS=United Kingdom Prospective Diabetes Study;
MDRD=Modification of Diet in Renal Disease;
HOT=Hypertension Optimal Treatment;
AASK=African American Study of Kidney Disease;
Bakris et al. Am J Kidney Dis. 2000;36:646-661;
Brenner et al. N Engl J Med. 2001;345:861-869;
Lewis et al. N Engl J Med. 2001;345:851-860.
2003 ESH/ESC Guidelines
Diuretics
AT1-receptor
blockers
ß-blockers
Calcium
antagonists
1-blockers
ACE inhibitors
CAD Risk Factors: Minimal and Optimal
Grundy SM, Circulation, 1999; American Heart Association Consensus Panel, Circulation, 1995; The Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure and the National High Blood Pressure Education Program Coordinating
Committee, Arch Intern Med, 1997.