Boston, MA- Statins lower the low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP). In a study published by Paul Ridker, M.D., et al, in the January 6, 2005 issue of The New England Journal of Medicine in Boston, the relationship between the LDL cholesterol and CRP levels achieved after treatment with 80 mg of atorvastatin or 40 mg of pravastatin was evaluated. Their data indicated that among patients with acute coronary syndromes, who are treated with a statin, achieving a target level of CRP of less than 2 mg per liter is associated with a significant improvement in event-free survival.  

In a study population derived from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) study, plasma samples of LDL and CRP were obtained as part of protocol. The relationship between LDL and CRP levels achieved after treatment with 80 mg of atorvastatin or 40 mg of pravastatin per day and the risk of recurrent myocardial infarction or death from coronary causes among 3,745 patients with acute coronary syndromes was evaluated.  

There was a linear relationship between the levels of LDL cholesterol achieved after statin therapy and the risk of recurrent myocardial infarction or death from coronary causes. Patients in whom statin therapy resulted in LDL cholesterol levels of less than 70 mg per deciliter had lower event rates than those with higher levels (2.7 vs. 4.0 events per 100 person-years, P=0.008). An identical difference was observed between those who had CRP levels of less than 2 mg per liter after statin therapy and those who had higher levels (2.8 vs. 3.9 events per 100 person-years, P=0.006). This effect was present at all LDL levels.  

Evaluation of the effectiveness of the two statins was also obtained. With regard to CRP, the median levels were similar in the atorvastatin and pravastatin groups at randomization (12.2 and 11.9 mg per liter, respectively; P=0.60). They were significantly lower in the atorvastatin group than in the pravastatin group at 30 days (1.6 vs. 2.3 mg per liter, P<0.001) and at the end of the study (1.3 vs. 2.1 mg per liter, P<0.001). Despite the greater ability of atorvastatin than pravastatin to reduce LDL and CRP levels, there was little evidence that either agent led to better clinical outcomes.

These data suggest clinical relevance for several reasons. First of all, strategies that aggressively lower cardiovascular risk by means of statin therapy should monitor inflammation as well as cholesterol. Next, the change in CRP and LDL levels were independent predictors of plaque regression after statin therapy. Thirdly, reducing inflammation, and thus the level of CRP, may alter the atherothrombotic process.  

In summary, this study demonstrates that the use of statin therapy to achieve target levels of both LDL cholesterol and CRP decreases the risk of recurrent myocardial infarction or death from coronary causes in patients with acute coronary syndromes. Thus, therapies designed to reduce inflammation may improve cardiovascular outcomes.  

Co-authors: Christopher P. Cannon, M.D., David Morrow, M.D., Nader Rifai, Ph.D., Lynda M.Rose, M.S., Carolyn H. McCabe, B.S., Marc Pfeffer, M.D., Ph.D, and Eugene Braunwald, M.D.