Epidemia Mundial de la vida moderna

Presentación del tema: "Epidemia Mundial de la vida moderna"— Transcripción de la presentación:

1 Epidemia Mundial de la vida moderna
Aterosclerosis Epidemia Mundial de la vida moderna

2 La Aterosclerosis, un Problema de Salud en México y en el Mundo
Cada 2 segundos muere en el mundo una persona por causas atribuibles a la aterosclerosis. En un año casi se han duplicado los casos de angina inestable a nivel mundial. Cada hora en México mueren ocho personas por enfermedades del corazón.

3 Objetivos Fundamentales de las Guías
Norteamericanas Europeas Consenso Mexicano de Lípidos OMS Control óptimo de los factores mayores de riesgo cardiovascular Promover estilos de vida saludable Incidencia de eventos vasculares coronarios, cerebrales y periféricos __de tipo Isquémico Prevenir la discapacidad y la muerte prematura Conocer y utilizar fármacos probados en la prevención y tratamiento de __las enfermedades cardiovasculares

4 ¿ Son las Guías del ATP-III vigentes ?
NECP ¿ Son las Guías del ATP-III vigentes ?

5 Aterosclerosis : Múltiples factores de riesgo
Diabetes Tabaco Dislipidemia Aterosclerosis Hipertensión Vida Sedentaria Obesidad

6 Dislipidemia y aterosclerosis
Figure 28 Atherogenic lipoproteins (e.g. LDL, apo B-rich particles like Lp-B:C-III) penetrate the arterial wall and induce: expression of adhesion molecules (which capture monocytes which then migrate into the intima); differentiation of macrophages (which release inflammatory cytokines); increased lipoprotein capture and penetration.

7 Programa Nacional de Educación sobre el Colesterol (National Cholesterol Education Program)
Lineamientos del III Panel de Tratamiento en Adultos (Adult Treatment Panel III, ATP III) Guidelines

8 Nuevos Equivalentes de Enfermedad Coronaria
>20% de riesgo a 10años de enfermedad coronaria (Framingham) Diabetes Otras formas de enfermedad aterosclerótica clínica: – Enfermedad arterial Periférica – Aneurisma aórtico abdominal – Enfermedad carotídea

9 Incidencia de IM a 7 años en una Población Finlandesa
IM Fatal o No fatal (%) 45.0 P < 0.001 18.8 20.2 P < 0.001 3.5 IM Previo Sin IM Sujetos no diabéticos IM Previo Sin IM Sujetos diabéticos (n=1373) (n=1059)

10 Nuevas Directrices: Diagnóstico
Clasificación: Col-LDL ( mg/dl ) < óptima subóptimo limítrofe alto alto  muy alto Col. Total ( mg/dl ) < deseable limítrofe alto > alto Col- HDL ( mg/dl ) < bajo > 60 * alto * Factor de riesgo “negativo” A dult T reatment P anel III N C E P

11 Nuevas Directrices: Diagnóstico
TRIGLICERIDOS: (mg/dl) < normal limítrofe alto alto > muy alto Factor de riesgo independiente para EAC Otras situaciones predisponentes: Diabetes Mellitus, Sx. Nefrótico, hepatopatías, alcoholismo, tabaquismo, fármacos (esteroides).

12 Diagnóstico y Estratificación de Riesgo
Estratificación del Riesgo Coronario Adultos > 20 años Perfil completo de lípidos: CT, LDL, HDL y TG. Cada 5 años Otros FRCV ? NCEP, Adult Treatment Panel III. JAMA. 2001;285:

13 Categorías de Tratamiento, LDL-C Metas y Puntos de Corte
Categoría del Riesgo Meta LDL-C Terapia con Fármaco Enfermedad Coronaria o Equivalente de riesgo <100 mg/dL 130 mg/dL*  2 Factores de Riesgo Riesgo a 10 años 10–20% Riesgo a 10 años <10% <130 mg/dL 130 mg/dL 160 mg/dL < 2 Factores de Riesgo <160 mg/dL 190 mg/dL * 100–129 mg/dL = después de cambios de estilo de vida, considerar estatinas, niacina, o fibratos

14 APO PL TG Lipoproteinas Esteres de Col Col Libre

15 Partículas Aterogénicas
Apolipoproteina B Medidas: No-HDL-C Atherogenic particles Not only is LDL-C a risk factor for cardiovascular disease, but triglyceride-rich lipoproteins—very low density lipoprotein (VLDL), VLDL remnants, and intermediate-density lipoprotein (IDL)—may also increase the risk of heart disease. The NCEP ATP III uses non-HDL-C principally as a surrogate for these atherogenic particles. VLDL VLDLR IDL LDL LDL Pequeña y Densa Lipoproteinas ricas en triglicéridos

16 Estilo de Vida y Aterosclerosis
Post. Paleolítico Neolítico Siglo 19 Siglo 21 Subsistencia Casa colectiva Alimentos procesados Grasa animales Fibras dietéticas Vida sedentaria Alto nivel de actividad física Genotipo estable Genotipo susceptible

17 El Síndrome Metabólico
Disminución a la tolerancia a la glucosa Hiperinsulinemia Hipertensión Desorden en la hemostasia Desorden en los lípidos * Trigliceridos elevados Obesidad visceral * LDL - colesterol normal o levemente elevado * HDL – C disminuido

18 >102 cm (>40 in) >88 cm (>35 in)
ATP III: El Síndrome Metabólico El diagnóstico se establece en presencia de  3 componentes Factor de Riesgo Nivel Definido Obesidad Abdominal (Circunferencia de la cintura) Hombre Mujer >102 cm (>40 in) >88 cm (>35 in) TG 150 mg/dL HDL-C <40 mg/dL <50 mg/dL Presión Sanguínea 130/85 mm Hg Glucosa en ayuno 110 mg/dL ATP III: the metabolic syndrome The NCEP ATP III guidelines define 5 components of the metabolic syndrome; 3 or more risk factors are required for the diagnosis of the metabolic syndrome. The low HDL-C criterion for women is higher than that defined for risk factor counting in the ATP III algorithm for primary prevention, and the blood pressure criterion is lower. A comparison of the ATP III risk factor–counting algorithm and the metabolic syndrome is given in the next two slides. Reference: Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:

19 Consecuencias Metabólicas de la Hipertrigliceridemia
Baja Densidad LDL Incremento Remanentes en Quilomicrón Disminución de HDL Hipertrigliceridemia Incremento de IDL Incremento Remanentes de VLDL Grundy, SM., “Cholesterol and Atherosclerosis: Diagnosis and Treatment” J.B. Lippincott Company, Philadelphia, 1980, página 27

20 ~10% Pérdida de Peso = ~30% Pérdida de Tejido Adiposo Visceral
Tejido Adiposo Subcutáneo Dieta Actividad Física Terapia Médica Tejido Adiposo Viseral Deteriorado Perfil Lípido Mejorado Dañado Sensibilidad a la Insulina Insulimia Glisemia Mejorado Susceptible a la Trombosisis Síntomas de Inflamación Dañado Mejorado Función Endotelial Obesidad Abdominal Cintura grande Obesidad Reducida Cintura chica Alto Riesgo-CHD Bajo

21 Puntos finales con Estatinas
Estudios Fármaco Reducción del Riesgo Coronario Prevensión Primaria AFCAPS/TexCAPS Lovastatin –40%* WOSCOPS Pravastatin –31%* Prevensión Secundaria 4S Simvastatin –34%* CARE –24%* LIPID Isquemia MIRACL Atorvastatin –26%** AVERT –36%** *IM fatal o no fatal; **eventos isquémicos

22 Implicaciones de estudios clínicos recientes para las guías de NCEP ATP III
Grupo de Expertos: Grundy, Cleeman, Bairey, Merz, Brewer, Clark, Hunninghake, Pasternak, Smith, Stone Reporte NCEP Avalado por: National Heart, Lung, and Blood Institute American Heart Association American College of Cardiology Implications of recent clinical trials for NCEP ATP III guidelines On the basis of clinical trial results published after the Adult Treatment Panel III (ATP III) guidelines of the U.S. National Cholesterol Education Program (NCEP) in 2001, updated recommendations have been issued by NCEP and endorsed by the National Heart, Lung, and Blood Institute, the American Heart Association, and the American College of Cardiology. Reference: Grundy SM, Cleeman JI, Bairey Merz CN, et al., for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:

23 Estudios clínicos posteriores al ATP III
HPS (simvastatin 40) PROSPER (pravastatin 40) ALLHAT-LLT (pravastatin 40) ASCOT-LLA (atorvastatin 10) PROVE IT (pravastatin 40 vs. atorvastatin 80) Post–ATP III clinical trials Since the ATP III guidelines were published, a number of large clinical event trials of statin therapy have been published, including the Heart Protection Study (HPS), Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial—Lipid-Lowering Trial (ALLHAT-LLT), Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA), and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT). References: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. Shepherd J, Blauw GJ, Murphy MB, et al., on behalf of the PROSPER study group. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360: ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002;288: Sever PS, Dahlöf B, Poulter NR, et al., for the ASCOT Investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003;361: Cannon CP, Braunwald E, McCabe CH, et al. Comparison of intensive and moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:

24 Estudio de Protección del Corazón: Diseño
20,536 adultos ingleses (40–80 años) Pacientes de alto riesgo: enfermedad coronaria, vascular periférica, DM-2 e hipertensión arterial Variable LDL-C inicial Tx: simvastatin 40 mg vs. placebo (tambien el brazo tratado con vitaminas) 5 años de estudio Heart Protection Study: design The Heart Protection Study (HPS) randomized more than 20,000 high-risk patients with total cholesterol 135 mg/dL or greater to receive simvastatin 40 mg/d or placebo. Mean baseline LDL-C was 131 mg/dL, and mean follow-up was 5 years. References: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.

25 Estudio de Protección del Corazón: Resultados Importantes
Reducción del riesgo en todos los niveles de LDL-C Reducción del riesgo en LDL-C <100 mg/dL Beneficio en pacientes ancianos Beneficio en pacientes diabéticos Heart Protection Study: major findings HPS demonstrated the clinical benefit of LDL-C–lowering simvastatin therapy regardless of baseline LDL-C, including LDL-C levels already at the goal recommended in the ATP III guidelines. In addition, benefit was observed in older patients and in patients with diabetes. References: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003;361:

26 Reducción de Eventos Vasculares de Acuerdo a niveles LDL-C (mg/dL)
% Reducción Relativa del Riesgo HPS: reduction in major vascular events according to baseline LDL-C (mg/dL) In HPS, simvastatin treatment reduced relative risk for major vascular events in patients whose baseline LDL-C was >130 mg/dL, 100–130 mg/dL, or <100 mg/dL. References: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. MRC/BHF Heart Protection Study website: -22% -22% -30%

27 Estudio Prove-it 4,162 pacientes con síndrome coronario agudo
Tx: pravastatina 40 mg vs. atorvastatina 80 mg Niveles de LDL-C con tratamiento: pravastatina 95 mg/dL, atorvastatina 62 mg/dL 2 años continuos de seguimiento 16% de reducción en los puntos finales compuestos con atorvastatina comparado con pravastatina PROVE IT In the Pravastatin or Atorvastatin Evaluation and Infection Therapy trial (PROVE IT), more than 4,000 patients with acute coronary syndrome and total cholesterol of 240 mg/dL or less (200 mg/dL in patients on lipid therapy) were randomized to receive intensive therapy with atorvastatin 80 mg/d or moderate therapy with pravastatin 40 mg/d. Intensive therapy reduced LDL-C to 62 mg/dL and reduced the composite primary endpoint (death, myocardial infarction, unstable angina requiring rehospitalization, revascularization after 30 days, and stroke) by 16% compared with moderate therapy, which reduced LDL-C to 95 mg/dL (within the LDL-C goal of <100 mg/dL recommended in the ATP III guidelines). Reference: Cannon CP, Braunwald E, McCabe CH, et al. Comparison of intensive and moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:

28 Estudio de Protección del Corazón (5 años)
Simvastatina 40 mg Riesgo de evento coronario 26% Reducción de eventos Simvastatina 40 mg Heart Protection Study (5-year trial) Since the ATP III guidelines were published, evidence from HPS was not supportive of the threshold model and has suggested that the relationship between LDL-C level and CHD risk is curvilinear (or possibly linear) across the full range of baseline LDL-C levels included in the study. In HPS, similar benefit on cardiovascular event reduction was provided with simvastatin therapy in patients whose baseline LDL-C was above or below the ATP III goal of 100 mg/dL. Reference: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. 22% Reducción de eventos 60 100 LDL-C (mg/dL)

29 Riesgo Relativo de evento coronario (Log Scale)
“Más bajo es mejor” 3.7 1 2.9 Riesgo Relativo de evento coronario (Log Scale) 2.2 1.7 1.3 "The lower, the better" The results of HPS and PROVE IT suggest that reducing LDL-C substantially below 100 mg/dL may provide additional benefit in high-risk patients. Neither of these trials indicated a lower threshold for LDL-C below which further LDL-C reduction did not provide further risk reduction. Reference: Grundy SM, Cleeman JI, Bairey Merz CN, et al., for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110: 1.0 40 70 100 130 160 190 LDL-C (mg/dL)

30 Candidatos a Metas Muy Bajas de LDL-C: < 70 mg/dL
Pacientes de muy alto riesgo Enfermedad Aterosclerosa establecida + multiples factores de riesgo (diabetes) + factores mayores de riesgo mal controlados (tabaquismo) + síndrome metabólico (TG altos, HDL-C bajo) + síndromes coronarios agudos (Prove-it) Candidates for very low LDL-C goal of <70 mg/dL Determining whether high-risk patients would benefit from the more intensive LDL-C goal of <70 mg/dL requires clinical judgment. Appropriate candidates would be very high risk patients such as those with established CHD or other atherosclerotic vascular disease, multiple risk factors, severe or poorly controlled risk factors, metabolic syndrome, or acute coronary syndromes.

31 ¿Qué hay de nuevo para pacientes con riesgo moderadamente alto?
Meta ATP III LDL-C : <130 mg/dL Nivel LDL-C 130 mg/dL: comenzar con fármacos y tratamiento dietético Nueva opción terapéutica: Meta de LDL-C <100 mg/dL (basada en ASCOT) Nivel de LDL-C 100–129 mg/dL: terapia opcional con fármacos (basada en ASCOT) What’s new for moderately high risk patients? On the basis of clinical trial evidence published since the ATP III guidelines, recommended modifications to the ATP III treatment algorithm for patients with moderately high risk (2 or more risk factors and estimated 10-year risk of 10–20%) include initiation of LDL-C–lowering drug therapy if LDL-C remains 130 mg/dL or greater with diet therapy (with an LDL-C goal of <130 mg/dL as in ATP III) and a therapeutic option of initiating LDL-C–lowering drug therapy in patients whose LDL-C is 100–129 mg/dL (at baseline or on diet therapy) to reduce LDL-C to <100 mg/dL.

32 ¿Que hay de Nuevo para los Pacientes de Alto Riesgo?
Meta de ATP III LDL-C : <100 mg/dL Para riesgo muy alto: meta opcional <70 mg/dL Para LDL-C 100 mg/dL, comenzar con el fármaco reductor de LDL simultaneamente con cambios en el estilo de vida Para LDL-C <100 mg/dL, fármaco reductor de LDL es una opción terapéutica Para TG altos/HDL-C bajo, considerar fibratos o ácido nicotínico con fármaco reductor de LDL What’s new for high-risk patients? On the basis of clinical trial evidence published since the ATP III guidelines, recommended modifications to the ATP III treatment algorithm for high-risk patients (CHD or CHD risk equivalent) include an optional LDL-C goal of <70 mg/dL for very high risk patients, simultaneous initiation of LDL-C–lowering drug therapy with therapeutic lifestyle changes in patients with LDL-C 100 mg/dL or greater, and the option of LDL-C–lowering drug therapy in patients with LDL-C <100 mg/dL at baseline. In high-risk patients with high triglycerides or low HDL-C, a fibrate or nicotinic acid may be considered in combination with an LDL-C–lowering drug.

33 ¿ Son las Guías del ATP-III vigentes ?
NECP ¿ Son las Guías del ATP-III vigentes ? 2001 2002 2003 2004 2005

34 Gracias ! G R A C I A S !