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-hyd roxy-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-infl ammatory effect of statins are not available. Objective to test the hypothesis that pravastation has anti-inflammatory ef fects 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 c ardiovascular disease (primary prevention cohort) and open-label study incl uding 1182 patients with known cardiovascular disease (secondary prevention cohort) who provided at least baseline and 12-week blood samples. The stud y was conducted in US office-based practices from February to December 2000 . Interventions Participants in the double-blind primary prevention trial wer e randomly assigned to receive 40 mg/d of pravastatin (n=865) or placebo (n =837) for 24 weeks. Participants in the secondary prevention cohort receive d 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 decr ease of 0.02 mg/dL in the pravastatin group while no change in CRP levels w as 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, bod y mass index, baseline lipid levels. presence of diabetes, and use of aspir in 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 lin ear regression analyses, the only significant predictors of change in CRP o n a log scale were randomized pravastatin allocation and baseline CRP level s (P<.001 for both). Similar reductions in CRP levels were observed at 12 w eeks (-14.3%) and 24 weeks (-13.1%) in the secondary prevention cohort trea ted with pravastatin (P<.005 for both). Conclusions In this prospective trial, pravastatin reduced CRP levels at bo th 12 and 24 weeks in a largely LDL-C-independent manner. These data provid e evidence that statin may have anti-inflammatory effects in additions to l ipid-lowering effects.