C-Reactive Protein, the Metabolic Syndrome, and Prediction of Cardiovascular Events in the Framingham Offspring Study

Abstract

Background— Inflammation (assessed by C-reactive protein [CRP]) and the metabolic syndrome (MetS) are associated with cardiovascular disease (CVD), but population-based data are limited. Methods and Results— We assessed the cross-sectional relations of CRP to the MetS (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition) in 3037 subjects (1681 women; mean age, 54 years) and the utility of CRP and the MetS to predict new CVD events (n=189) over 7 years. MetS (≥3 of 5 traits) was present in 24% of subjects; mean age-adjusted CRP levels for those with 0, 1, 2, 3, 4, or 5 MetS traits were 2.2, 3.5, 4.2, 6.0, or 6.6 mg/L, respectively ( P trend <0.0001). In persons with MetS, age-adjusted CRP levels were higher in women than men (7.8 versus 4.6 mg/L; P <0.0001). MetS and baseline CRP were individually related to CVD events (for MetS: age-sex-adjusted hazard ratio [HR], 2.1; 95% CI, 1.5 to 2.8; for highest versus lowest CRP quartile: HR, 2.2; 95% CI, 1.4 to 3.5). Greater risk of CVD persisted for MetS and CRP even after adjustment in a model including age, sex, MetS (HR, 1.8; 95% CI, 1.4 to 2.5), and CRP (HR, 1.9; 95% CI, 1.2 to 2.9). The c-statistic associated with the age- and sex-adjusted model including CRP was 0.72; including MetS, 0.74; and including CRP and MetS, 0.74. Conclusions— Elevated CRP levels are related to insulin resistance and the presence of the MetS, especially in women. Although discrimination of subjects at risk of CVD events using both MetS and CRP is not better than using either phenotype alone, both CRP and MetS are independent predictors of new CVD events.