C-reactive protein in the prediction of cardiovascular and overall mortality in middle-aged men: a population-based cohort study

AIMS: Cut-offs for C-reactive protein concentrations have been recommended for risk stratification, but little is known about how these cut-offs predict cardiovascular risk in population-based cohorts. We therefore assessed the association of C-reactive protein levels with cardiovascular mortality in a population-based cohort of 2321 middle-aged men stratified by the presence of cardiovascular disease (CVD) at baseline. METHODS AND RESULTS: C-reactive protein concentrations were categorized according to current recommendations (1 and 3 mg/L). During the 15 year follow-up, 77 men without CVD and 121 men with CVD at baseline died of CVD. In men without CVD at baseline (n=1476), age-adjusted cardiovascular mortality was 4.1-fold higher (95% CI 2.1-8.2) for C-reactive protein levels between 3.0 and 9.9 mg/L at baseline than for C-reactive protein levels <1.0 mg/L. In men with CVD at baseline (n=845), the corresponding age-adjusted cardiovascular mortality was 3.3-fold higher (95% CI 2.0-5.3). Adjustment for conventional CVD risk factors attenuated the risk somewhat. Further adjustment for dietary and lifestyle factors and factors related to insulin resistance did not affect the association. Classification of C-reactive protein by tertiles gave qualitatively similar results, but identified twice as many men at high risk. C-reactive protein levels also predicted overall mortality. CONCLUSION: Currently, recommended cut-offs for C-reactive protein levels identify men at risk for cardiovascular and overall death independently of conventional and other risk factors in a population-based sample of middle-aged men with and without CVD at baseline. Lower cut-offs may better identify men at high risk for cardiovascular death, but improvement of current recommendations will require standardization of C-reactive protein assays.