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

2. RISICO  PREVENTIE

4. “klassieke” risicomodellen  nieuwere risicofactoren  “beeldvorming”  genetisch onderzoek (I) gezonde levenswijze  risicofactormodificatie  medicatie (II)

5. Lipid core Adventitia stabiele plaque

6. Lipid core Adventitia Thrombus instabiele plaque

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

9. RISICO BEPALEN (I)

10. 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

12. 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

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

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

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

16. “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….

17. 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 27939 apparently healthy American women

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

20. 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. 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. 1 Clin Radiol.2003;58:378

21. Rudd. Circulation.2002;105:2708

22. 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-1 ,-1 ,-6,-10, P-selectin,CD-14 receptor,TNF  lipoxygenase  THROMBOSIS :  -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,  2 adrenergic receptor, metalloproteinase- 1 and 12… Yamada et al. NEJM.2002;347:1916

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

24. 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;350:29 470 healthy middle-aged men and women from the LA atherosclerosis study

25. RISICO REDUCTIE (II)

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

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

29. Lyon Diet Heart Study meer brood meer wortel- en bladgroenten  foliumzuur) meer fruit meer vis  -poly-onverzadigde vetzuren) runds-, varkens en lamsvlees gevogelte boter en margarine olijfolie en koolzaadolie  linoleenzuur) de Lorgeril. Circulation 1999;99:779

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

31. 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

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

33. 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

35. 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 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

37. risicofactormodificatie (II) BMI < 25 kg/m 2 en buikomtrek < 102 (88) cm bloeddruk < 140/90 mmhg (<130/85 mmhg) totaal cholesterol < 190 mg/dl (5 mmol/ L) LDL cholesterol < 115 mg/dl (3 mmol/L) diabetes : HbA 1c < 7.5% De Backer. EHJ.2003;24:1601

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

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

40. aspirin for primary prevention of chd Sanmuganathan PS. Heart 2001;85:265

41. other antiplatelet agents… Collagen Thrombin TxA 2 ASA (Fibrinogenreceptor) Clopidogrel TxA 2 ADP GP IIb/IIIa Activation Schafer AI Am J Med 1996;101:199–209 COX ADP

42. 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

43. CAPRIE Lancet 1996;348:1329

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

45. statines 79.495

46. 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

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

51. ace-inhibitoren post-mi long-term post-mi: SAVE (n=2231,captopril ) AIRE (n=2006, ramipril) TRACE (n=1749, trandolapril) (ischemic) heart failure: CONSENSUS (n=253,enalapril) VHeFT II (n=804,enalapril) SOLVD (n=2569+4228,enalapril)

52. Heart Outcome Protection Study 9.297 pts > 55 yrs without heart failure but with increased cardiovascular risk (atherosclerosis or diabetes +  1 risk factor). 10 mg ramipril vs placebo 4.5 yrs of follow-up 1477 MAVE (nonfatal mi + nonfatal stroke + cv death) NEJM 2000;342:145

53. myocardial infarction + stroke + cardiovascular mortality 651 pts 826 pts NEJM 2000;342:145

54. beta-blockers post-mi long-term post-mi: B-HAT (n=,3837propranolol) BBPP (n=13.679) (ischemic) heart failure: CIBIS (n=350,bisoprolol) carvedilol (n=521) CIBIS II (n=1316,bisoprolol) MERIT-HF (n=2606,metoprolol) COPERNICUS (n=1533,carvedilol)

55. Beta-blockers and reduction of cardiac events in noncardiac surgery. Auerbach JAMA 2002;287:1435

56. medicatie (III) plaatjesremmers statines ace-inhibitoren beta-blockers … foliumzuur  3-vetzuren

57. prices www.socmut.be

58. expanding statin use … is causing financial heartburn UK : 8% of adults are HPS-like patients and only 23% are currently treated with statins (Bandolier) Ireland : statin budget is doubling every 15 to 18 months and now accounts for over 6% of all drug expenditures (Barry) the Netherlands : 800 million Euro/yr or 50 Euro/person is spended on statins (Simoons) Mitka JAMA 2003;290:2243

59. the “polypill” A strategy to reduce cardiovascular disease by more than 80%. NJ Wald, MR Law. BMJ 2003;326:1419-23. A cure for cardiovascular disease : combination teratment has enormous potential. A. Rodgers. BMJ 2003;326:1408-9.

60. besluit cardiovasculair risico : laag hoog preventiemaatregelen : gezonde levenswijze risicofactoren asa,statines,ace-i,…