Transcript DISLIPEMIAS UN FACTOR DE RIESGO SIEMPRE VIGENTE

DISLIPEMIAS
UN FACTOR DE RIESGO
SIEMPRE VIGENTE
Dr Marcos Baroni
Dpto de Prevención Cardiovascular
(Instituto Modelo de Cardiología – Córdoba)
INTERHEART : Risk of AMI Associated With Risk Factors
Risk Factors
Contro Cases
l
(%)
(%)
OR (99% CI)
Adjusted for
Age, Sex,
and Smoking
OR (99% CI)
Adjusted for
All Other
Risk Factors
Apo B/ Apo A
20
33.5
3.87 (3.39 -4.42)
3.25 (2.82 – 3.76)
Current
smoking
26.8
45.2
2.95 (2.72 -3.20)
2.87 (2.58-3.19)
Diabetes
7.5
18.5
3.08 (2.77-3.72)
2.37 (2.07-2.71)
Hypertension
21.9
39.0
2.48 (2.30-2.68)
1.91 (1.74-2.10)
Abdominal
obesity (3 vs 1)†
33.3
46.3
2.22 (2.03-2.42)
1.62 (1.45-1.80)
LDL cholesterol





Strongly associated with atherosclerosis and CVD
events
10% increase results in an approximate 20%
increase in CHD risk
Most of the cholesterol in plasma is found in LDL
particles
Smaller denser LDL are more atherogenic than
larger, less dense particles
Risk associated with LDL-C is increased by other
risk factors:low HDL
smoking
 hypertension
 diabetes

Incidence of recurrent MI
HDL cholesterol

HDL-C has a protective effect for risk of
atherosclerosis and CHD

Epidemiological studies show the lower the HDL-C
level, the higher the risk for atherosclerosis and CHD

low level (<40 mg/dL, 1 mmol/L) increases risk

HDL-C tends to be low when triglycerides are high

HDL-C is lowered by smoking, obesity and physical
inactivity
Rol de la apolipoproteínas de las
HDL en la remoción de las LDL
oxidadas

Transferencia CETP de las LDL oxidada a
las HDL

Las LDL oxidadas son reducidas por las
apolipoproteínas de las HDL

Hígado capta los lípidos reducidos por las
HDL más rápidamente que las LDL
Low HDL-C is an Independent
Predictor of CHD Risk even when LDL-C is
Low
3
2
25
1
65
85 mg/l
100 mg/l
0
160 mg/l
220 mg/l
COLESTEROL HDL
Factores Modificadores de las
HDL

Efectos Antiinflamatorios:
1.
Apo A1 mimetizada
Ejercicio
Dieta baja en grasas
Grasas Poliinsaturadas
Estatinas
2.
3.
4.
5.
Factores Modificadores de las
HDL

1.
2.
3.
4.
5.
6.
7.
8.
Efectos Proinflamatorios:
Ateroesclerosis coronaria
DBT
Hemodiálisis
Grasas saturadas
Infecciones
Artritis Reumatoidea
Cirugías
LES
¿Por Qué Pro inflamatorias?

Disminución Apo A1

Daño de Apo A1 por la mieloperoxidasa

Inflamación asociada a estrés oxidativo

(puede llevar a la alteración y reducción de las
enzimas antioxidantes)
Nuevos Tests evaluando función
HDL

Determinación Quimiotaxis de Monocitos

Moléculas de Adhesión

Estimulación por el Cobre

( todos en fase experimental)
CETP
ILLUMINATE: Major results
HDL (mg/dl) 3 meses
Torcetrabip
Radio para muerte
CV
< 60
1.00
60 - 70
0.67
71 - 80
0.47
81 - 93
0.57
> 93
0.43
N Engl J Med 2007;356:1304-1316
ILLUMINATE: Major results
End
point
Eventos
Mayores
Atorvastatin
(n: 7534)
373
Atorvatatin +
Torcetrabip
(n:7533)
464
Hazard Ratio
(95 % CI)
1.25
P
0.001
(1.09- 1.44)
Muertes
59
93
1.58
0.006
(1.14 – 2.19)
N Engl J Med 2007;356:1304-1316
Riesgo de EC segun Trigliceridos
( Framingham Heart Study)
N=5127
3
Men
2.5
Women
2
1.5
1
0.5
0
50
100
150
200
250
300
350
400
Hipertrigliceridemia + HDL bajo
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Es usual en síndrome metabólico
Es un patrón muy común en aterosclerosis
temprana
Asociada a la tríada de ↑ILDL y VLDL con
LDL pequeña-densa
Tríada lipídica = dislipidemia aterogénica
TRIGLICERIDOS POSPRANDIALES:
FACTOR DE RIESGO CV
La trigliceridemia posprandial (2 hs.)
es un FR independiente para
aterosclerosis temprana
Enfermedad coronaria
Enfermedad carotídea
(IMT)
Boquist S et al. Circulation 17:723,1999
•Aumento de triglicéridos posprandiales causan disfunción
endotelial.
•El bloqueo del SRA (IECA y Ant. At1) previenen esta disfunción
Wilmink HW et al. JACC 34:140,1999
TRIGLICÉRIDOS Y GLUCOSA POST PRANDIALES
Dislipemia en el Síndrome
Metabólico

Hipertrigliceridemia por sobreproducción
de VLDL



Disminución de las HDL
Cambios cualitativos de las LDL
COLESTEROL NO HDL
COLESTEROL NO HDL = COL TOTAL – COL HDL
Therapeutic Targets for Low-Density Lipoprotein (LDL) Cholesterol
and Non-High-Density Lipoprotein (non-HDL) Cholesterol as
Recommended by the National Cholesterol Education Program
Adult Treatment Panel III
Risk Level
LDL
Cholesterol
Goal
Non-HDL
Cholesterol
Goal
CHD and CHD risk
equivalents*
<100 mg/dL
<130 mg/dL
Multiple (2+) risk factors
(10-year CHD risk
</=20%)
0-1 Risk factor
<130 mg/dL
<160 mg/dL
<160 mg/dL
<190 mg/dL
Effect of lipid-modifying therapies on lipids
TC
LDL
HDL
TG
Patient
tolerability
Bile acid
sequestrants
Down
20%
Down
15–30%
Up
3–5%
Neutral or up
Poor
Nicotinic acid
Down
25%
Down
25%
Up
15–30%
Down
20–50%
Poor to
reasonable
Fibrates
Down
15%
Down
5–15%
Up
20%
Down
20–50%
Good
Probucol
Down
25%
Down
10–15%
Down
20–30%
Neutral
Reasonable
Statins*
Down
19–37%
Down
25–50%
Up
4–12%
Down
14-29%
Good
-
Down
18%
Up
1%
Down
8%
Good
Therapy
Ezetimibe
TC–total cholesterol, LDL–low density lipoprotein, HDL–high density lipoprotein, TG–triglyceride.
*Daily dose of 40 mg of atorvastatin, simvastatin, pravastatin and fluvastatin.
Yeshurun D, Gotto AM. Southern Med J 1995;88(4):379–391. Knopp RH. N Engl J Med 1999;341:498–
511. Product Prescribing Information. Gupta EK, Ito MK. Heart Dis 2002;4:399-409.
NCEP ATP III: LDL-C Goal
(2004 proposed modifications)
190 -
High Risk
Moderately
High Risk
Moderate
Risk
Lower
Risk
CHD or CHD risk
equivalents
≥ 2 risk
factors
≥ 2 risk
factors
< 2 risk
factors
(10-yr risk
>20%)
(10-yr risk
10-20%)
(10-yr risk
<10%)
goal
160
LDL-C level
mg/dL
160 -
goal
130
mg/dL
130 -
goal
100
mg/dL
goal
130
mg/dL
or
optional
100
mg/dL*
100 -
or
optional
70
mg/dL*
Existing LDL-C goals
Proposed LDL-C goals
70 *Therapeutic option
70 mg/dL =1.8 mmol/L; 100 mg/dL = 2.6 mmol/L; 130 mg/dL = 3.4 mmol/L; 160
mg/dL = 4.1 mmol/L
Grundy SM et al. Circulation 2004;110:227-239.
ESTATINAS
↓
↓ HMG CoA reductasa
↓
↓Niveles intrahepatocitarios de colesterol
↓
↑ Expresión del receptor de LDL
↓
↓LDL circulante
↓
↓ Colesterol Plasmático
Efecto Adverso
Efecto
General
Pérdida de apetito, pérdida de peso
Piel
Rásh cutáneo
Sistema Nervioso Pérdida de concentración, cefalea
Gastrointestinal
Dolor abdominal, naúseas, diarrea
Hígado
Hepatitis, aumento de transaminasas
Músculos
Dolor muscular, ↑ CPK , miositis,
rabdomiólisis
Síndrome simil lupus
Sistema Inmune
Unión Proteica
Disminución de unión a proteínas de
warfarina
Is Lower Better?
Relationship between LDL-C and CV Event Rate
Cholesterol balance
Is Lower Better?
Relationship between LDL-C and CV Event Rate
Event rate %
30
- Primary Prevention
- Secondary Prevention
4S - Pl
Rx - Statin therapy
25
Pl - Placebo
20
4S - Rx
LIPID - Pl
15
LIPID - Rx
10
CARE - Rx
PROSPER - Rx
HPS - Pl
HPS - Rx
ALLHAT - Rx
5
ASCOT - Rx
0
70(1.8)
CARE - Pl
PROSPER - Pl
WOSCOPS - Rx
AFCAPS/TexCAPS - Pl
AFCAPS/TexCAPS
- Rx
90(2.3)
WOSCOPS - Pl
ALLHAT - Pl
110(2.8)
ASCOT - Pl
130(3.4)
150(3.9)
170(4.4)
190(5.0)
210(5.4)
LDL-C achieved mg/dL (mmol/L)
Ballantyne CM et al. Am J Cardiol 1998;82:3Q–12Q.
The Anglo-Scandinavian Cardiac Outcomes Trial Lipid
Lowering Arm: Extended Observations 2 Years After Trial
Eur Heart J. 2008;29(4):499-508. ©2008
¿Qué Podemos Hacer con las
HDL?




Considerar que los pacientes con disminución de
HDL tienen riesgo incrementado para enfermedad
cardiovascular
Conocer que las enfermedades crónicas alteran la
calidad de las HDL (proinflamatorias)
aumentando el riesgo CV (a pesar de valores
elevados de HDL)
El uso de estatinas, fibratos, niacinas y medidas no
farmacológicas pueden reducir el riesgo CV
Anacetrapib ???
FIBRATOS

Modo de Acción
 ↑ actividad de lipoprotein lipasa (lipolisis
de trigliceridos, ↑ clearance)
 ↓ lipolisis en el tejido adiposo, ↓
liberación AGL
 ↓ secrecion de VLDL por el hígado
 ↓ captación de AGL por el hígado
 ↑ HDL moderadamente
FIBRATOS

– Efectos Adversos
Cálculos Biliares (disconfort epigástrico,
intolerancia a CCK, meteorismo)
 Usar con precaución en ptes c/ patolog
biliar, mujeres, obesos
 Miopatia (injuria muscular)
 Debilidad, o dolor muscular inusual
 Puede aumentar risgo de miopatia
inducida por estatinas cuando se usan
conjuntamente (rabdomiolisis ha
ocurrido raramente)
 Desplaza warfarina y ciclosporina de la
albúmina
plasmática. Necesidad de disminuir
dosis de warfarina. Chequear RIN:

TERAPEÚTICA INSUFICIENTE ??
FISH OILS AND STATINS



Marine fish oil rich in omega 3 fatty acids lower
trigliceride levels and may be effective in
combination with statins to treat patients with
combined hyperlipidemia
Fish oils plus statin may often be an alternative to
fibrate plus statin
Fish oils may have other cardiovascular effects
complementary to those of statins, such as:
- Reduction in malignant ventricular dysrithmias
- Antithrombotic effects
- Improved endothelial reactivity /relaxation
- Antiinflammatory effects
Bays HE et al – Expert Opin Pharmacother 2003 -4 -1901 -1938
Kris Etherton – Circulation 2002 – 106 -2747 - 2757
PPAR- y AGONIST AND STATINS

Statins are commonly used to reduce CHD risk in patients
with type 2 diabetes and the metabolic syndrome

PPAR y agonist, improved glucose control and may have lipid effects
complementary to those of statins




LDL particle size may be increased with PPAR y
Trigliceride levels are decreased with PPAR y
HDL are increased with PPAR y
The metabolic effects of PPAR y agonist may be complementary to the lipid
effects of statins in patients with type 2 diabetes and metabolic syndrome
Bays HE- Brithis Journal of Diabetes and
Vascular Disease 2003 -3 356-360
insberg HN –Am J of Cardiol 2003 – 91 : 29E-39E
Benefits
of
Intensive
Lifestyle
Benefits
of
Intensive
Benefits of Intensive Lifestyle
Lifestyle
Changes
on
TG
Levels
Changes
on
TG
Changes on TG Levels
Levels
Within DPP,
 TG
Within
levelsDPP,
fell
TG levels fell
significantly
more
more
insignificantly
the group with
in the group
with
intensive
lifestyle
intensive lifestyle
intervention
than in
intervention
in
the
metformin than
group
the metformin group
 Aimed to reduce
weight
Aimedby
to7%
reduce
with

weight by
7% with
a low-fat
diet
a low-fat
diet
150
minutes
of
moderate
150 minutes
of
exercise
moderate
exercise
per
week
per week
180
180
160
160
160
160
140
140
140
120
120
100
100
DPP=Diabetes Prevention Program.
Baseline
Year 1
Year 2
Year 3
TG (mg/dL)
TG (mg/dL)

Lifestyle
Lifestyle
National Institute of Diabetes & Digestive & Kidney Diseases of the NIH.
Accessed at http://www.niddk.nih.gov/welcome/releases/8_8_01.htm.
Ratner R et al. Diabetes Care. 2005;28:888-894.
ACTIVIDAD
FISICA
AEROBICA
MUCHAS GRACIAS