Thrombosis and thromboembolism - part 2 ppt

Inflammation and Arterial Thrombosis 21 dian LDL value in AFCAPS/TexCAPS; such patients had a number-to-needed- to-treat of 42, a level considered not only cost-effective but cost-saving. However, lovastatin therapy was also effective in reducing the risk of first-ever coronary events among study participants with low levels of LDL cholesterol who had above-average levels of CRP. Specifically, the magnitude of risk reduction asso- ciated with statin use for those with above-average CRP levels but normal lipid levels was almost identical to that observed among those with above-median cholesterol levels. Moreover, among such patients who had elevated levels of CRP but normal lipid levels, the event rate was just as high as that observed among those with overt hyperlipidemia. For these individuals, the number- needed-to-treat was also very low (NNT ϭ 48). By contrast, lovastatin appeared to have no effect in participants in AFCAPS/TexCAPS who had below-average LDL levels and below-average CRP levels. As might be expected, the absolute event rate was very low in this group, who had normal to low lipid levels and no evidence of inflammation. In this low-risk population defined by both LDL and CRP, the NNT was exceptionally large and statin utility cost-ineffective. Finally, like the PRINCE study, the AFCAPS/TexCAPS CRP substudy showed that lovastatin reduced CRP levels in a lipid-independent manner, this time at 1- year follow-up. When viewed together, data from the PRINCE study (196) and the AFCAPS/TexCAPS CRP substudy (200) confirm that elevated levels of CRP are a potent independent predictor of heart attack and stroke, and that combining CRP with cholesterol levels provides an improved tool for global risk prediction. Moreover, both of these large studies demonstrate clearly that statin therapy leads to approximately 15% reductions in CRP levels. Last, although hypothesis-gener- ating, the AFCAPS/TexCAPS CRP substudy also suggests that statins may sig- nificantly reduce vascular risk even in individuals who do not have overt hyperlip- idemia. IV. SUMMARY Pathological and experimental data suggest that atherosclerosis is an inflamma- tory disease. In support of the clinical extension of these observations, prospec- tive epidemiological data provide consistent evidence of an association between sensitive markers of systemic inflammation and the risk of future cardiovascular events. In particular, high-sensitivity testing for CRP identifies apparently healthy individuals who are at higher risk for vascular events at 5 or more years after blood sampling, as well as individuals with stable and unstable coronary disease who are more likely to suffer recurrent atherothrombosis. 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(events/pt/yr) 740 .2 5 32. 6 20 7.6 50.8 155 131 24 16 0 .21 0 .25 0. 12 0.31 3 12 278 36 3 32 44.8 52 52 0 5 0 0.17 0.19 0.00 0.015 0 ASA dose varied between 80 and 325 mg/day Source: Modified from Refs 14, 16, 17, 29 , 30 54 Crowther and Ginsberg 3 Diagnostic Pathway A congenital or acquired hypercoagulable state should be suspected in all patients presenting with unusual forms of thrombosis or in whom thrombosis. .. 2 Plasma Folate and Homocysteine Concentrations Before and After Folic Acid Fortification (Framingham Offspring Study Participants not Taking Vitamin B Supplements) Characteristic Plasma folate Ͻ 3 ng/mL (%) Baseline Follow-up Fasting total homocysteine Ͼ 13 µmol/L (%) Baseline Follow-up Study group a (n ϭ 24 8) Control group (n ϭ 553) 22 .0 (17.3 26 .7) b 1.7 (0.0–5.4) 25 .3 (22 .1 28 .4) 20 .7 (18.3 23 .2) ... Homocysteine and Vascular Disease Risk 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 47 to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study Circulation 1998; 98 :20 4 Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ Folate and vitamin B 6 from diet and supplements in relation to risk of... prevention of thromboembolism, high-intensity warfarin (target INR Ͼ 2. 8) has been evaluated in five settings: (1) patients with tissue heart valves (27 ); (2) patients with acute deep vein thrombosis (28 ); (3) patients with APLA (16 ,29 ,30); (4) patients with previous stroke (31); and (5) patients with coronary artery disease (26 ) High-intensity warfarin was not more effective than standard-intensity warfarin... synthesize tissue factor Blood 1993; 82: 513– 520  32 177 178 179 180 181 1 82 183 184 185 186 187 188 189 190 191 1 92 193 Morrow and Ridker Zouki C, et al Prevention of in vitro neutrophil adhesion to endothelial cells through shedding of L-selectin by C-reactive protein and peptides derived from Creactive protein J Clin Invest 1997; 100: 522 – 529 Wolbink GJ, et al CRP-mediated activation of complement in... interleukin-6 in baboons Euro Cyto Netw 1994; 5 :27 5– 28 1 Stouthard JM, et al Interleukin-6 stimulates coagulation, not fibrinolysis, in humans Thromb Haemost 1996; 76:738–7 42 Biasucci LM, et al Increasing levels of interleukin (IL )-1 Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events Circulation 1999; 99 :20 79 20 84 Ridker... women; positively associated with age; and inversely associated with vitamin B 12 and folate Reference ranges were developed for American adults, and, as an example, the 95th percentile of homocysteine range was 12. 9 µmol/L in men and 10 .2 µmol/L in women 40 to 59 years of age (8) 38 Wilson Figure 2 Relations between homocysteine levels and plasma levels of vitamin B 12 and folate (From Ref 6.) Naturally... total and HDL cholesterol in determining risk of first myocardial infarction Circulation 1998; 97 :20 07 20 11 Rifai N, Ridker P A Proposed cardiovascular risk assessment algorithm employing high-sensitivity C-reactive protein and lipid screening Clin Chem 20 01; 47 :28 – 30 Vaughan CJ, Murphy MB, Buckley BM Statins do more than just lower cholesterol Lancet 1996; 348:1079–10 82 Ridker PM, et al Long-term... for beta -2 glycoprotein-1, a circulating plasma glycoprotein Anticardiolipin antibodies are likely associated 49 50 Crowther and Ginsberg with titer-dependent increases in the risk of thrombosis and recurrent pregnancy loss ACA, and to a lesser extent lupus anticoagulants, may demonstrate specificity for certain anionic phospholipids, in particular phosphatidylserine, phosphatidylinositol, and phosphatidylcholine... (14, 16,17), and in patients with an ACA, the risk of thromboembolism is higher in those with a previous history of thromboembolism than in those without such a history ( 12) This increased risk of recurrent thromboembolism has also been reported in patients with stroke (18 20 ), with venous thromboembolism (14), and with other types of thromboembolism (16,17) In summary, patients with APLA, particularly . group a Control group Characteristic (n ϭ 24 8) (n ϭ 553) Plasma folate Ͻ 3 ng/mL (%) Baseline 22 .0 (17.3 26 .7) b 25 .3 (22 .1 28 .4) Follow-up 1.7 (0.0–5.4) 20 .7 (18.3 23 .2) Fasting total homocysteine Ͼ 13. Inflammation and Arterial Thrombosis 21 dian LDL value in AFCAPS/TexCAPS; such patients had a number-to-needed- to-treat of 42, a level considered not only cost-effective but cost-saving. However, lovastatin. molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atheroscle- rosis Risk In Communities (ARIC) study. Circulation 1997; 96: 421 9– 422 5. 111.