C-Reactive Protein Adds to the Predictive Value of Total and HDL Cholesterol in Determining Risk of First Myocardial Infarction

Abstract

Background —C-reactive protein (CRP) is a sensitive marker of inflammation, and elevated levels have been associated with future risk of myocardial infarction (MI). However, whether measurement of CRP adds to the predictive value of total cholesterol (TC) and HDL cholesterol (HDL-C) in determining risk is uncertain. Methods and Results —Among 14 916 apparently healthy men participating in the Physicians’ Health Study, baseline levels of CRP, TC, and HDL-C were measured among 245 study subjects who subsequently developed a first MI (cases) and among 372 subjects who remained free of cardiovascular disease during an average follow-up period of 9 years (controls). In univariate analyses, high baseline levels of CRP, TC, and TC:HDL-C ratio were each associated with significantly increased risks of future MI (all P values <0.001). In multivariate analyses, models incorporating CRP and lipid parameters provided a significantly better method to predict risk than did models using lipids alone (all likelihood ratio test P values <0.003). For example, relative risks of future MI among those with high levels of both CRP and TC (RR=5.0, P =0.0001) were greater than the product of the individual risks associated with isolated elevations of either CRP (RR=1.5) or TC (RR=2.3). In stratified analyses, baseline CRP level was predictive of risk for those with low as well as high levels of TC and the TC:HDL-C ratio. These findings were virtually identical in analyses limited to nonsmokers and after control for other cardiovascular risk factors. Conclusions —In prospective data from a large cohort of apparently healthy men, baseline CRP level added to the predictive value of lipid parameters in determining risk of first MI.