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This study is the latest Cyclopamine and largest genome-wide association study failing to demonstrate a significant association between genetically elevated CRP levels and risk of CHD. Last, a recent meta-analysis of 46,557 patients with CHD and 147,861 controls demonstrated a null association among CRP-related genotypes, traditional risk factors, and risk of CHD (33). These animal and human genetic data indicate a lack of causal relationship between CRP and CHD. In contrast, similar Mendelian analyses of LDL-C and lipoprotein(a) are compatible with causal effects in CHD 35?and?36. An association of hsCRP with risk for CVD has been described in many studies (37). The MRFIT (Multiple Risk Factor Intervention Trial) was the first of many primary prevention, prospective epidemiological studies to show a strong relationship between levels of hsCRP and mortality from CHD in high-risk middle-aged men (9). A similar association between increasing hsCRP levels and subsequent rate of MI and stroke was found in an analysis of apparently healthy men (38). In the WHS (Women��s Health Study), LDL-C��an established causative biological marker of atherosclerosis��was compared with hsCRP in 27,939 healthy women who were followed for an average of 8 years for MI, ischemic stroke, coronary revascularization, or CV death. BML-190 After adjustment for age and conventional risk factors, hsCRP was a stronger predictor of CV events than LDL-C. The primary endpoint was twice as likely in those with hsCRP in the fourth quintile between 2.10 and 4.19?mg/l as compared with levels of 0.49 mg/l (relative risk [RR]: 2.0; 95% CI: 1.3 to 3.0). LDL-C levels in the fourth quintile (132 to 154 mg/dl) had a 30% excess risk of CV events as compared with those with LDL-C?BI 2536 molecular weight (10% to 20%) risk for mortality from CHD or nonfatal MI in 10 years. A literature-based meta-analysis of 22 studies was performed on behalf of the U.S. Preventive Services Task Force to determine whether hsCRP testing should be incorporated into current guidelines as an adjunctive screening tool for CHD. An hsCRP level >3 mg/l was independently associated with a 60% excess risk in incident CHD as compared with levels?