Long-term effects of pravastatin on plasma concentration of C-reactive protein

Background-Elevated plasma concentrations of C-reactive protein (CRP) are a ssociated with increased cardiovascular risk. We evaluated whether long-ter m therapy with pravastatin, an agent that reduces cardiovascular risk, migh t alter levels of this inflammatory parameter. Methods and Results-CRP levels were measured at baseline and at 5 years in 472 randomly selected participants in the Cholesterol and Recurrent Events (CARE) trial who remained free of recurrent coronary events during follow-u p. Overall, CRP levels at baseline and at 5 years were highly correlated (r =0.60, P<0.001). However, among those allocated to placebo, median CRP leve ls and the mean change in CRP tended to increase over time (median change, +4.2%; P=0.2 and mean change, +0.07 mg/dL; P=0.04). By contrast, median CRP levels and the mean change in CRP decreased over time among those allocate d to pravastatin (median change, -17.4%; P=0.004 and mean change, -0.07 mg/ dL; P=0.002). Thus, statistically significant differences were observed at 5 years between the pravastatin and placebo groups in terms of median CRP l evels (difference, -21.6%; P=0.007), mean CRP levels (difference, -37.8%; P =0.002), and absolute mean change in CRP (difference, -0.137 mg/dL; P=0.003 ). These effects persisted in analyses stratified by age, body mass index, smoking status, blood pressure, and baseline lipid levels. Attempts to rela te the magnitude of change in CRP to the magnitude of change in lipids in b oth the pravastatin and placebo groups did not reveal any obvious relations hips. Conclusions-Among survivors of myocardial infarction on standard therapy pl us placebo, CRP levels tended to increase over 5 years of follow-up. In con trast, randomization to pravastatin resulted in significant reductions in t his inflammatory marker that were not related to the magnitude of lipid alt erations observed. Thus, these data further support the potential for nonli pid effects of this agent.