Ridker PM et al. (2005) C-reactive protein levels and outcomes after statin therapy. N Engl J Med 352: 20–28

In patients with known cardiovascular disease, lowering LDL cholesterol to target levels is the main focus of statin therapy. Ridker et al. hypothesized that patients whose C-reactive protein (CRP) levels were lowered using statin therapy would have better outcomes than those whose CRP levels remained high.

The study included 3,745 patients from the PROVE IT–TIMI 22 trial. All had recent myocardial infarction or high-risk unstable angina and were randomized in a 1:1 ratio to intensive therapy with atorvastatin (80 mg daily) or moderate therapy with pravastatin (40 mg daily). LDL-cholesterol and CRP levels were measured in plasma samples taken at the 30-day follow-up visit; there was very little correlation between the 'achieved' levels of LDL and CRP.

During the mean follow-up of 2 years, the risk of recurrent myocardial infarction or cardiovascular death was significantly lower in patients with achieved LDL-cholesterol levels below 1.8 mM/l (70 mg/dl) than in those with higher levels. An almost identical reduction in risk was seen in patients with achieved CRP levels below 2 mg/l compared with those with higher levels, irrespective of the achieved LDL-cholesterol level. The best outcomes by far were seen among those who lowered both LDL and CRP to <1.8 mM/l (70/dl) and <2 mg/l respectively, suggesting that physicians need to consider this dual goal to best manage their patients.

The study indicates that treating inflammation is an important aspect of cardiovascular risk reduction in patients with acute coronary syndromes, and the authors propose that CRP levels should be monitored in patients receiving statins. An ongoing study known as JUPITER is investigating whether this approach is also appropriate for primary prevention.