Long-Term Effects of Pravastatin on Plasma Concentration of C-reactive Protein

Abstract

Background —Elevated plasma concentrations of C-reactive protein (CRP) are associated with increased cardiovascular risk. We evaluated whether long-term therapy with pravastatin, an agent that reduces cardiovascular risk, might 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-up. 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 levels 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 allocated 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 levels (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 relate the magnitude of change in CRP to the magnitude of change in lipids in both the pravastatin and placebo groups did not reveal any obvious relationships. Conclusions —Among survivors of myocardial infarction on standard therapy plus placebo, CRP levels tended to increase over 5 years of follow-up. In contrast, randomization to pravastatin resulted in significant reductions in this inflammatory marker that were not related to the magnitude of lipid alterations observed. Thus, these data further support the potential for nonlipid effects of this agent.