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

TLDR

C‑reactive protein is a sensitive inflammatory marker whose elevated levels have been linked to future myocardial infarction risk. The study aimed to determine whether adding CRP measurement to total and HDL cholesterol improves MI risk prediction. Researchers measured baseline CRP, total cholesterol, and HDL cholesterol in 14,916 healthy men, followed for an average of nine years, and compared 245 incident MI cases to 372 controls. Multivariate models that incorporated CRP and lipid parameters predicted MI risk significantly better than lipids alone, with high CRP and total cholesterol yielding a relative risk of 5.0—greater than the product of their individual risks—and CRP remained predictive across all cholesterol strata and after adjustment for other risk factors.

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.