Effect of statin therapy on C-reactive protein levels - The Pravastatin Inflammation/CRP Evaluation (PRINCE): A randomized trial and cohort study

Context Plasma levels of the inflammatory biomarker C-reactive protein (CRP) predict cardiovascular risk, and retrospective studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (stations) may lower CRP in a manner largely independent of low-density lipoprotein cholesterol (LDL-C). However, prospective trial data directly evaluating this anti-inflammatory effect of statins are not available. Objective to test the hypothesis that pravastation has anti-inflammatory effects as evidenced by CRP reduction. Design, Setting, and Participants Community-based, prospective, randomized, double-blind trial including 1702 men and women with no prior history of cardiovascular disease (primary prevention cohort) and open-label study including 1182 patients with known cardiovascular disease (secondary prevention cohort) who provided at least baseline and 12-week blood samples. The study was conducted in US office-based practices from February to December 2000. Interventions Participants in the double-blind primary prevention trial were randomly assigned to receive 40 mg/d of pravastatin (n=865) or placebo (n=837) for 24 weeks. Participants in the secondary prevention cohort received 40 mg/d of open-label pravastatin for 24 weeks. Main Outcome Measure Change in CRP levels from baseline to 24 weeks. Results In the primary prevention trial, compared with placebo, pravastatin reduced median CRP levels by 16.9% (P<.001) at 24 weeks, reflecting a decrease of 0.02 mg/dL in the pravastatin group while no change in CRP levels was observed in the placebo group. This effect was seen as early as 12 weeks (median reduction in CRP with pravastatin, 14.7%; P<.001) and was present among all prespecified subgroups according to sex, age, smoking status, body mass index, baseline lipid levels. presence of diabetes, and use of aspirin or hormone replacement therapy. No significant association was observed between baseline CRP and baseline LDL-C levels, end-of-study CRP and end-of-study LDL-C levels, or change in CRP and change in LDL-C over time. In linear regression analyses, the only significant predictors of change in CRP on a log scale were randomized pravastatin allocation and baseline CRP levels (P<.001 for both). Similar reductions in CRP levels were observed at 12 weeks (-14.3%) and 24 weeks (-13.1%) in the secondary prevention cohort treated with pravastatin (P<.005 for both). Conclusions In this prospective trial, pravastatin reduced CRP levels at both 12 and 24 weeks in a largely LDL-C-independent manner. These data provide evidence that statin may have anti-inflammatory effects in additions to lipid-lowering effects.