Aterosclerosis y sindrome metabolico

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  • 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.
  • 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.
  • 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;285:2486-2497.
  • 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;110:227-239.
  • 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 20 536 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;360:1623-30. 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;288:2998-3007. 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;361:1149-1158. 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;350:1495-1504.
  • 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 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.
  • 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 20 536 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;361:2005-2016.
  • 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 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. MRC/BHF Heart Protection Study website: http://www.hpsinfo.org
  • 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;350:1495-1504.
  • 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 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.
  • "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;110:227-239.
  • 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.
  • 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.
  • 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.
  • Aterosclerosis y sindrome metabolico

    1. 1. Epidemia Mundial de la vida modernaEpidemia Mundial de la vida modernaAterosclerosis
    2. 2. La Aterosclerosis, unProblema de Saluden México y en el Mundo• Cada 2 segundos muere en el mundo una persona porCada 2 segundos muere en el mundo una persona porcausas atribuibles a la aterosclerosis.causas atribuibles a la aterosclerosis.• En un año casi se han duplicado los casos de anginaEn un año casi se han duplicado los casos de anginainestable a nivel mundial.inestable a nivel mundial.• Cada hora en México mueren ocho personas porCada hora en México mueren ocho personas porenfermedades del corazón.enfermedades del corazón.
    3. 3. Incidencia de eventos vasculares coronarios, cerebrales y periféricos__de tipo IsquémicoObjetivos Fundamentales delas GuíasNorteamericanas Consenso Mexicanode LípidosOMSEuropeasControl óptimo de los factores mayores de riesgo cardiovascularPromover estilos de vida saludablePrevenir la discapacidad y la muerte prematuraConocer y utilizar fármacos probados en la prevención y tratamiento de__las enfermedades cardiovasculares
    4. 4. ¿ Son las Guías del ATP-III¿ Son las Guías del ATP-IIIvigentes ?vigentes ?NECP
    5. 5. Aterosclerosis :Múltiples factores de riesgoAterosclerosisTabacoDislipidemiaDiabetesHipertensión Vida Sedentaria Obesidad
    6. 6. Dislipidemia y aterosclerosisDislipidemia y aterosclerosis
    7. 7. Programa Nacional de EducaciónPrograma Nacional de Educaciónsobre el Colesterol (Nationalsobre el Colesterol (NationalCholesterol Education Program)Cholesterol Education Program)Lineamientos del III Panel de Tratamiento en Adultos(Adult Treatment Panel III, ATP III) Guidelines
    8. 8. Nuevos EquivalentesNuevos Equivalentesde Enfermedad Coronariade Enfermedad Coronaria>20% de riesgo a 10años de enfermedad coronaria(Framingham)DiabetesOtras formas de enfermedad aterosclerótica clínica:– – Enfermedad arterial Periférica– – Aneurisma aórtico abdominal– – Enfermedad carotídea
    9. 9. 01020304050Incidencia de IM a 7 aIncidencia de IM a 7 aññososen una Población Finlandesaen una Población FinlandesaIMFataloNofatal(%)(n=1373) (n=1059)18.83.545.020.2IM Previo Sin IMSujetos no diabéticosIM Previo Sin IMSujetos diabéticosP < 0.001P < 0.001
    10. 10. Nuevas Directrices:DiagnósticoCol-LDL ( mg/dl )• < 100 óptima• 100-129 subóptimo• 130-159 limítrofe alto• 160-189 alto• ≥ 190 muy altoCol. Total ( mg/dl )• < 200 deseable• 200-239 limítrofe alto• > 240 altoCol- HDL ( mg/dl )• < 40 bajo• > 60 * alto * Factor de riesgo “negativo”Clasificación:A dultT reatmentP anelIIIN C E P
    11. 11. TRIGLICERIDOS: (mg/dl)• < 150 normal• 150-199 limítrofe alto• 200-499 alto• > 500 muy altoFactor de riesgo independiente para EACOtras situaciones predisponentes:Diabetes Mellitus, Sx. Nefrótico, hepatopatías, alcoholismo, tabaquismo,fármacos (esteroides).Nuevas Directrices:Diagnóstico
    12. 12. Diagnóstico y Estratificación deRiesgoEstratificación 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;285:2486-2497.
    13. 13. CategorCategoríías de Tratamiento, LDL-Cas de Tratamiento, LDL-CMetas y Puntos de CorteMetas y Puntos de CorteCategoría del Riesgo Meta LDL-CTerapia conFármacoEnfermedad Coronaria oEquivalente de riesgo <100 mg/dL ≥130 mg/dL*≥ 2 Factores de RiesgoRiesgo a 10 años 10–20%Riesgo a 10 años <10%<130 mg/dL<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. 14. TGEsteres deColPLColLibreAPOLipoproteinas
    15. 15. Partículas AterogénicasPartículas AterogénicasApolipoproteina BApolipoproteina BNo-HDL-CNo-HDL-CMedidas:Medidas:Lipoproteinas ricasLipoproteinas ricasen triglicéridosen triglicéridosVLDLVLDL VLDLVLDLRRIDLIDL LDLLDL LDLLDLPequeñaPequeñay Densay Densa
    16. 16. AlimentosprocesadosGrasa animalesFibras dietéticasVida sedentariaEstilo de Vida y AterosclerosisEstilo de Vida y AterosclerosisPost. Paleolítico Neolítico Siglo 19 Siglo 21Genotipo estable Genotipo susceptibleSubsistenciaCasa colectivaAlto nivel deactividad física
    17. 17. El Síndrome MetabólicoEl Síndrome MetabólicoDisminución a latolerancia a la glucosaHiperinsulinemia HipertensiónObesidad visceralDesorden en lahemostasiaDesorden en los lípidos* Trigliceridos elevados* LDL - colesterol normal olevemente elevado* HDL – C disminuido
    18. 18. ATP III: El Síndrome MetabólicoATP III: El Síndrome MetabólicoEl diagnóstico se establece en presencia de ≥ 3 componentesFactor de Riesgo Nivel DefinidoObesidad Abdominal(Circunferencia de la cintura)HombreMujer>102 cm (>40 in)>88 cm (>35 in)TG ≥150 mg/dLHDL-CHombreMujer<40 mg/dL<50 mg/dLPresión Sanguínea ≥130/≥85 mm HgGlucosa en ayuno ≥110 mg/dL
    19. 19. Consecuencias MetabólicasConsecuencias Metabólicasde la Hipertrigliceridemiade la HipertrigliceridemiaHipertrigliceridemiaBaja DensidadLDLIncremento Remanentesen QuilomicrónDisminución de HDLIncrementode IDLIncrementoRemanentes de VLDLGrundy, SM., “Cholesterol and Atherosclerosis: Diagnosis and Treatment”J.B. Lippincott Company, Philadelphia, 1980, página 27
    20. 20. ~10% Pérdida de Peso = ~30%~10% Pérdida de Peso = ~30%Pérdida de Tejido AdiposoPérdida de Tejido AdiposoVisceralVisceralTejido AdiposoSubcutáneo DietaActividad FísicaTerapia MédicaObesidadAbdominalCintura grandeObesidadReducidaCintura chicaTejidoAdiposoViseralRiesgo-CHDAlto BajoDeterioradoDañadoDañadoMejoradoMejoradoMejoradoPerfil LípidoSensibilidad a la InsulinaInsulimiaGlisemiaSusceptible a la TrombosisisSíntomas de InflamaciónFunción Endotelial
    21. 21. *IM fatal o no fatal; **eventos isquémicosPuntos finales con EstatinasPuntos finales con EstatinasEstudios FármacoReducción del RiesgoCoronarioPrevensión PrimariaAFCAPS/TexCAPS Lovastatin –40%*WOSCOPS Pravastatin –31%*Prevensión Secundaria4S Simvastatin –34%*CARE Pravastatin –24%*LIPID Pravastatin –24%*IsquemiaMIRACL Atorvastatin –26%**AVERT Atorvastatin –36%**
    22. 22. Implicaciones de estudiosImplicaciones de estudiosclínicos recientes para las guíasclínicos recientes para las guíasde NCEP ATP IIIde NCEP ATP IIIGrupo de Expertos: Grundy, Cleeman,Bairey, Merz, Brewer, Clark, Hunninghake,Pasternak, Smith, StoneReporte NCEPAvalado por:– National Heart, Lung, and Blood Institute– American Heart Association– American College of Cardiology
    23. 23. Estudios clínicos posterioresEstudios clínicos posterioresal ATP IIIal ATP IIIHPS (simvastatin 40)PROSPER (pravastatin 40)ALLHAT-LLT (pravastatin 40)ASCOT-LLA (atorvastatin 10)PROVE IT (pravastatin 40 vs. atorvastatin 80)
    24. 24. Estudio de Protección del Corazón:Estudio de Protección del Corazón:DiseñoDiseño20,536 adultos ingleses (40–80 años)Pacientes de alto riesgo: enfermedadcoronaria, vascular periférica, DM-2 ehipertensión arterialVariable LDL-C inicialTx: simvastatin 40 mg vs. placebo (tambien elbrazo tratado con vitaminas)5 años de estudio
    25. 25. Estudio de Protección del Corazón:Estudio de Protección del Corazón:Resultados ImportantesResultados ImportantesReducción del riesgo en todos los nivelesde LDL-CReducción del riesgo en LDL-C <100mg/dLBeneficio en pacientes ancianosBeneficio en pacientes diabéticos
    26. 26. Reducción de Eventos VascularesReducción de Eventos Vascularesde Acuerdo a niveles LDL-C (mg/dL)de Acuerdo a niveles LDL-C (mg/dL)%ReducciónRelativadelRiesgoLDL-CLDL-C<100<100LDL-CLDL-C100–130100–130LDL-CLDL-C>130>130-22%-22%-30%-30%-22%-22%-45-30-150
    27. 27. Estudio Prove-itEstudio Prove-it4,162 pacientes con síndrome coronario agudoTx: pravastatina 40 mg vs. atorvastatina 80 mgNiveles de LDL-C con tratamiento: pravastatina 95mg/dL, atorvastatina 62 mg/dL2 años continuos de seguimiento16% de reducción en los puntos finales compuestoscon atorvastatina comparado con pravastatina
    28. 28. Estudio de Protección del CorazónEstudio de Protección del Corazón(5 años)(5 años)01Riesgo deeventocoronario100LDL-C (mg/dL)Simvastatina40 mg6026% Reducciónde eventos22% Reducciónde eventosSimvastatina40 mg
    29. 29. ““Más bajo es mejor”Más bajo es mejor”RiesgoRelativode eventocoronario(Log Scale)3.72.92.21.71.31.0LDL-C (mg/dL)40 70 100 130 160 19001
    30. 30. Candidatos a Metas Muy BajasCandidatos a Metas Muy Bajasde LDL-C: < 70 mg/dLde LDL-C: < 70 mg/dLPacientes 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)
    31. 31. ¿Qué hay de nuevo para pacientes¿Qué hay de nuevo para pacientescon riesgo moderadamente alto?con riesgo moderadamente alto?Meta ATP III LDL-C : <130 mg/dLNivel LDL-C ≥130 mg/dL: comenzar confármacos y tratamiento dietéticoNueva opción terapéutica: Meta de LDL-C<100 mg/dL (basada en ASCOT)Nivel de LDL-C 100–129 mg/dL: terapiaopcional con fármacos (basada en ASCOT)
    32. 32. ¿Que hay de Nuevo para los¿Que hay de Nuevo para losPacientes de Alto Riesgo?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 fármacoreductor de LDL simultaneamente con cambios en elestilo de vida– Para LDL-C <100 mg/dL, fármaco reductor de LDL esuna opción terapéutica– Para TG altos/HDL-C bajo, considerar fibratos o ácidonicotínico con fármaco reductor de LDL
    33. 33. ¿ Son las Guías del ATP-III¿ Son las Guías del ATP-IIIvigentes ?vigentes ?NECP2001 2002 2003 2004 2005
    34. 34. GraciasGracias! G R A C I A S !

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