HsCRP and Risk ofCardiovascular Events in Primary Prevention

Prospective epidemiological studies indicate that hsCRP is a predictor of MI or CHD mortality (10,12,20,21,38-58), stroke (10,12,39,41,42,59-62), peripheral vascular disease (11,63), congestive heart failure (64,65), atrial fibrillation (66), and sudden cardiac death (67). The association between hsCRP and subsequent CVD has been observed in men and women, in the middle aged and elderly, in high- and usual-risk populations, and in the United States and Europe. The relation is apparent even after many years of follow-up. For example, elevated hsCRP levels at baseline were predictive of 17-yr coronary mortality in the Multiple Risk Factor Intervention Trial (38) and sudden cardiac death in the Physicians' Health Study (67). Among Japanese-American men participating in the Honolulu Heart Program, hsCRP was a strong predictor of MI (53) and thromboembolic stroke (61) up to two decades after initial blood samples were collected.

Epidemiological studies generally indicate that persons with baseline hsCRP levels in the top quartile of the sample distribution have a two- to threefold increase in the likelihood of experiencing a future vascular event than those in the bottom hsCRP quartile. In most instances, the association between hsCRP and subsequent vascular events has a linear "dose-response" shape and is independent of the risk factors commonly assessed in clinical settings and included in global cardiovascular prediction algorithms such as those derived from the Framingham Heart Study—age, smoking, hypertension, dyslipid-emia, and diabetes. In 2000, a meta-analysis of 14 prospective studies (2557 cases; mean follow-up of 8 yr) of hsCRP and risk of nonfatal MI or CHD death yielded a summary relative risk (RR) of 1.9 (95% confidence interval [CI]: 1.5-2.3) for individuals in the top tertile of baseline hsCRP compared with those in the bottom tertile (45). Each of the studies included in the meta-analysis adjusted for smoking and "some standard vascular risk factors."

More recently, findings from several major prospective studies, including the Women's Health Study (12), the Atherosclerosis Risk in Communities (ARIC) study (21), the Nurses' Health Study (58), and the Health Professionals Follow-up Study (58) in the United States; the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Augsburg study in Germany (56); and the Reykjavik Study in Iceland (57), have conclusively demonstrated that hsCRP provides prognostic information beyond that available from traditional cardiovascular risk factors. In these studies, hsCRP levels were interpreted in

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