Effects of Statins on Nonlipid Serum Markers Associated with Cardiovascular Disease: A Systematic Review

Background: Statins reduce cardiovascular events to a greater extent than can be explained by their effect on lipids. Several studies have attempted to elucidate mechanisms by which statins reduce cardiovascular risk. Purpose: To summarize the effects of statins on nonlipid serum markers and to correlate statins' effect on serum markers with lipid levels and cardiovascular outcomes. Data Sources: MEDLINE (1980 to 2003) search limited to English-language articles. Study Selection: Studies reporting original data in at least 10 participants on the effect of statins on outcomes of interest, excluding studies of cerivastatin, drug combinations, and patients with organ transplants. Data Extraction: Study design, sample size, treatment, and outcome data extracted on the basis of preestablished criteria. When appropriate, meta-analysis was performed by using a random-effects model. Data Synthesis: All statins are effective at lowering C-reactive protein levels, and the effect is not dose-dependent. Studies do not demonstrate a correlation between statins' effects on C-reactive protein levels and on lipids or cardiovascular outcomes. Statins do not affect fibrinogen levels, and limited data suggest little effect on lipid oxidation, tissue plasminogen activator, or plasminogen activator inhibitor. Platelet aggregation data are inconclusive. Conclusions: Among nonlipid serum markers examined, only C-reactive protein levels are statistically significantly affected by statins. These findings suggest that statin-mediated anti-inflammatory effects may contribute to the ability of statins to reduce risk for cardiovascular disease. Overall, however, available data are insufficient to support recommendations for using nonlipid serum markers in decisions regarding statin therapy for individual patients.