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risicofactoren en cardiovasculaire preventie : stand van zaken ?

risicofactoren en cardiovasculaire preventie : stand van zaken ?. J.Van Cleemput, MD, PhD, dienst cardiologie, KUL-UZ GHB. RISICO  PREVENTIE. RISICO  PREVENTIE. “klassieke” risicomodellen  nieuwere risicofactoren  “beeldvorming”  genetisch onderzoek (I).

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risicofactoren en cardiovasculaire preventie : stand van zaken ?

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  1. risicofactoren en cardiovasculaire preventie : stand van zaken ? J.Van Cleemput, MD, PhD, dienst cardiologie, KUL-UZ GHB

  2. RISICO  PREVENTIE

  3. RISICO  PREVENTIE “klassieke” risicomodellen  nieuwere risicofactoren  “beeldvorming”  genetisch onderzoek (I) gezonde levenswijze  risicofactormodificatie  medicatie (II)

  4. stabiele plaque Lipid core Adventitia

  5. instabiele plaque Thrombus Lipid core Adventitia

  6. age-standardized mortality( males 1990/1991) Atlas of Mortality in Europe

  7. RISICO BEPALEN(I)

  8. high risk ? European guidelines • established coronary heart disease, peripheral arte-ry disease or atherosclerotic cerebrovascular disease • asymptomatic patients with : • diabetes type 2 or type 1 with microalbuminuria • total (LDL) cholesterol > 320 (240) mg/dl or BP > 180/110 mmhg • close relatives with early (men < 55 yrs and women < 65 yrs) onset atherosclerotic cardiovascular disease • multiple risk factors resulting in a  5% 10-year risk of fatal cardiovascular event De Backer. EHJ.2003;24:1601

  9. SCORE system • 12 European cohort studies • 205.178 men and women 20  80 yrs. • gender, age, smoking, sbp and total cholesterol or total/HDL cholesterol • 10 yr. risk of any fatal “atherosclerotic” endpoint Conroy.EHJ 2003;24:987

  10. SCORE system Conroy.EHJ 2003;24:987

  11. Belgium France Greece Italy Luxembourg Spain Switzerland Portugal Fig. 2. Ten-year risk of fatal cardiovascular disease in populations at low cardiovascular disease risk. Chart based on total cholesterol.

  12. Denmark Finland Germany Norway Russia Scotland Sweden UK Fig. 1. Ten-year risk of fatal cardiovascular disease in populations at high cardiovascular disease risk. Chart based on total cholesterol.

  13. “nieuwere” risicofactoren • apolipoprotein B, small dense LDL cholesterol, oxLDL cholesterol, Lp(a)… • hs-CRP, SAA, sICAM-1, IL-6,…. • homocysteine, fibrinogen, von Willebrand factor, tissue factor, PAI-1….

  14. 27939 apparently healthy American women Figure 3. hs CRP provides prognostic information at all levels of LDL cholesterol and at all levels of the Framingham Risk Score. Data adapted from reference 6 Ridker et al.NEJM 2002;347:1557

  15. “beeldvorming” • carotid-intima media thickness • electron beam computer tomography • multi-slice CT • MRI • fluorodeoxyglucose-PET/CT

  16. Fig. 1. Multislice CT coronary angiography. (a) An axial section of the heart at the level of the aortic sinuses. The left ventricle (LV) and left atrium (LA) are marked and the right coronary artery is seen arising from the aorta (Ao). (b) The same patient but at the level of the left main stem. An area of calcification is noted in the left anterior descending artery and sequential axial sections suggested a significant lesion prior to the calcification in the proximal vessel segment (arrow). Fig. 2. Three-dimensional reconstructions of multislice CT coronary angiography (same patient as in Fig. 1). Volume-rendering techniques have been used to "remove" the pulmonary trunk, right ventricular outflow tract, both atrial appendages and part of the left atrium to allow visualization of the course of the coronary arteries (Cx, circumflex artery; RCA, right coronary artery). The appearance of the proximal left anterior descending artery (arrow) provides further evidence of a significant lesion. Fig. 3. (a and b) Two-dimensional "angiograms" derived from the three-dimensional reconstruction on the same patient. (a) The normal (large) circumflex artery and (b) the smaller left anterior descending artery, with a severe proximal stenosis (arrow). (c) The comparative invasive coronary angiogram (left anterior oblique, cranial angulation) confirming the severe proximal left anterior descending artery lesion. Clin Radiol.2003;58:378

  17. Rudd. Circulation.2002;105:2708

  18. genetica looking for polymorphisms in genes coding for : LIPIDS : apolipoprotein-A-I,-B,-C-III,-E, hepatic lipase, lipoproteinlipase,LDL receptor–related protein, Lp(a),… INFLAMMATION : Il-1a,-1b,-6,-10, P-selectin,CD-14 receptor,TNFa,lipoxygenase,... THROMBOSIS : b-fibrinogen, coagulation factor V, VII, XII, XIIIA, prothrombin, vWf, TFPI, PAI type1, PAF, platelet endothelial cell adhesion molecule,… MISCELLANEOUS : ace, AT-II receptor type1, angiotensinogen, ANP, b2 adrenergic receptor, metalloproteinase-1 and 12… Yamada et al. NEJM.2002;347:1916

  19. Dwyer et al. NEJM 2004;350:29

  20. 470 healthy middle-aged men and womenfrom the LA atherosclerosis study Means were adjusted for age, sex, height, racial or ethnic group, smoking status, level of physical activity, dietary intake of saturated fat, and intake of alcohol by analysis of covariance. D denotes deletion alleles, A addition alleles, and W common allele (five tandem Sp1 binding motifs). P values are for the differences between indicated genotype groups. Dwyer et al. NEJM 2004;350:29

  21. RISICO REDUCTIE (II)

  22. “gezonde levenswijze”(I) risicofactormodificatie (II) medicatie (III)

  23. “gezonde levenswijze”(I) • “gezonde” voeding • rookstop • 4 tot 5 maal per week 20 tot 30 minuten fysieke activiteit De Backer. EHJ.2003;24:1601

  24. Lyon Diet Heart Study • meer brood • meer wortel- en bladgroenten(foliumzuur) • meer fruit • meer vis(w-3-poly-onverzadigde vetzuren) • runds-, varkens en lamsvlees gevogelte • boter en margarine olijfolie en koolzaadolie(a-linoleenzuur) de Lorgeril. Circulation 1999;99:779

  25. Lyon Diet Heart Study ° M. de Lorgeril. Lancet 1994;343:1454. * M. de Lorgeril. Circulation 1999;99:779.

  26. nurses’ health study • 7.401 women with type 2 diabetes • never smokers past smokers current smokers : 114, 15  34 and >35 cigarettes/day • 20 yrs of follow-up • 724 all-cause mortality (I) 289 cardiovascular mortality (I) 237 cancer mortality Al-Delaimy WK. Diabetes Care 2001;24:2043

  27. *adjusted for age, HRT, hypertension, cholesterol, family history, physical activity

  28. women’s health initiative observational study • 73.743 postmenopausal women 50 to 79 years free of diagnosed cv disease and cancer • physical activity questionaires : walking + exercise => MET (hr/week) • 3.2 yrs of follow-up • 287 nonfatal mi and 58 coronary death (I) 1521 cardiovascular events (I) Manson JE. NEJM 2002;347:716

  29. nurses’ health study • 84.129 women 34 to 59 years free of diagnosed cv disease, cancer and diabetes • >15, 114, stopped smoking and never smoked >10, 5.1  10, 0.1  5.0 and 0 g alcohol/day <23, 23  24.9, 25  29.9 and >30 bmi >5.5, 3.6  5.5, 2.3  3.5, 1  2.2 and < 1 hr of exercise/wk 1,2,3,4 and 5 diet “score” (ao. fibers, n-3 fatty acids, folate, PUFA/SFA) • 14 yrs of follow-up • 832 nonfatal mi and 296 coronary death (I) Stampfer MJ. NEJM 2000;343:16

  30. risicofactormodificatie (II) • BMI < 25 kg/m2 en buikomtrek < 102 (88) cm • bloeddruk < 140/90 mmhg (<130/85 mmhg) • totaal cholesterol < 190 mg/dl (5 mmol/ L) LDLcholesterol < 115 mg/dl (3 mmol/L) • diabetes : HbA1c < 7.5% De Backer. EHJ.2003;24:1601

  31. medicatie (III) plaatjesremmers statines ace-inhibitoren beta-blockers …

  32. antiplatelet therapy in high risk patients Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71

  33. aspirin for primary prevention ofchd Sanmuganathan PS. Heart 2001;85:265

  34. other antiplatelet agents… Clopidogrel ADP ADP CollagenThrombinTxA2 GP IIb/IIIa Activation (Fibrinogen receptor) COX TxA2 ASA Schafer AIAm J Med 1996;101:199–209

  35. CAPRIE • 19.185 pts with “atherosclerosis” : recent ischaemic stroke, recent mi or symptomatic peripheral arterial disease • 75 mg clopidogrel vs 325 mg asa • 1-3 yrs follow-up • ischaemic stroke + mi + cv death Lancet 1996;348:1329

  36. CAPRIE Lancet 1996;348:1329

  37. CURE (NEJM 2001;345:494) CREDO (JAMA 2002;288:2411) …

  38. statines 79.495

  39. HPS • 20.536 pts 40-80 yrs and “vascular” disease or diabetes mellitus or (treated hypertension and male and > 65 yrs) • simvastatine 40 mg vs placebo • total mortality and cardiovascular mortality and non-cardiovascular mortality (I) • MAVE = MACE + strokes + revascularisations (II) Lancet 2002;360:7-22

  40. Lancet 2002;360:7-22

  41. Lancet 2002;360:7-22

  42. Lancet 2002;360:7-22

  43. statin = aspirin 0.74  1.68 Euro/d  0.08  0.13 Euro/d

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