C-Reactive Protein and Risk of Cardiovascular Disease in Men and Women From the Framingham Heart Study

Abstract

Background Determination of C-reactive protein (CRP) level has been suggested to improve cardiovascular disease (CVD) risk assessment. This study examines the utility of CRP levels to assess CVD risk in a community setting. Methods We performed a prospective observational cohort study on a community population sample. A total of 1949 men and 2497 women without CVD from the Framingham Heart Study underwent CVD risk factor assessment. Initial CVD events during 8 years of follow-up were recorded. Results There were 283 major CVD and 160 major coronary heart disease incident events. Age-, sex-, and multivariable-adjusted analyses generally used CRP level categories of less than 1, 1 to 3, and greater than 3 mg/L. In age- and sex-adjusted models, the traditional risk factors and elevated CRP levels indicated increased risk. The age- and sex-adjusted relative risk (RR) and 95% confidence interval (CI) of CRP level greater than 3 mg/L for major CVD was elevated (RR, 1.60; 95% CI, 1.19-2.14), with evidence of attenuation (RR, 1.22; 95% CI, 0.90-1.66) in multivariable models. The C statistic, a measure of the discriminatory capability of the prediction models, was 0.74 for prediction of major CVD with age and CRP level. In multivariable models that included traditional risk factors, the C statistic was 0.78, a value that was unchanged with the addition of CRP to the multivariable model. Similar relations were noted for major coronary heart disease events. Conclusion Elevated CRP level provided no further prognostic information beyond traditional office risk factor assessment to predict future major CVD and major coronary heart disease in this population sample. Traditional risk factors for coronary heart disease (CHD) and cardiovascular disease (CVD) have been shown to effectively predict vascular disease events.1-3 Age, sex, blood pressure, total cholesterol level, high-density lipoprotein cholesterol (HDL-C) level, and cigarette smoking have been considered key factors to assess risk of vascular disease, using continuous or categorical variables. In addition, type 2 diabetes mellitus is highly related to CVD risk, and disease management guidelines in the United States now consider this diagnosis a coronary disease risk equivalent because it augments vascular disease risk so markedly.4,5 Considerable interest exists in moving beyond traditional risk factors to predict CHD events. Although traditional risk factors account for much of the risk for CHD events, and at least 1 risk factor precedes 87% to 100% of CHD deaths, not all CHD risk is explained by the combined effect of traditional risk factors.6 The situation that stirs the greatest interest is screening of middle-aged and older individuals who have yet to experience clinical CVD. The factors and procedures that might improve CHD risk assessment in this situation are being scrutinized in observational studies that have follow-up for incident events.