BACKGROUND There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. METHODS We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. RESULTS The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P<0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of “low” (<10%), “intermediate” (10% to <20%), and “high” (≥20%) (P<0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of ≥20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. CONCLUSIONS In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)

miological studies have reported positive associations between the risk of coronary heart disease (CHD) and plasma fibrinogen levels. Fibrinogen is the major coagulation protein in blood by mass, the precursor of fibrin, and an important determinant of blood viscosity and platelet aggregation. [38][39][40][41] Because fibrinogen levels can be reduced considerably by lifestyle interventions that also affect levels of established risk factors (such as regular exercise, smoking cessation, and moderate alcohol consumption), there is interest in the possibility that measurement (or modification) of fibrinogen may help in disease prediction or prevention. [38][39][40]42 A meta-analysis of published data from 18 such studies, involving about 4000 CHD cases, indicated a relative risk of 1.8 (95% confidence interval [CI], 1.6-2.0) per 1-g/L increase in plasma fibrinogen level. 43 However, such analyses are not able to provide detailed assessments of the nature of any independent association of fibrinogen level with CHD or with other vascular and nonvascular outcomes. [43][44][45] This meta-analysis differs from previous analyses in several ways that should increase its reliability and scientific value. First, it is large and comprehensive: the data comprise 6944 first nonfatal myocardial infarction (MI) or stroke events and 13 210 deaths (cause-*The Authors/Writing Committee, Authors/Members, and Other Members of the Fibrinogen Studies Collaboration are listed at the end of this article.

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Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.