Phospholipase A 2 Enzymes, High-Dose Atorvastatin, and Prediction of Ischemic Events After Acute Coronary Syndromes

Background— Secretory phospholipase A2 (sPLA2 ) and lipoprotein-associated phospholipase A2 (Lp-PLA2 ) are enzyme biomarkers of increased cardiovascular risk and targets of emerging therapeutic agents. Their relationship to cardiovascular events in the setting of high-dose statin therapy compared with placebo in patients with acute coronary syndrome is not known.Methods and Results— sPLA2 and Lp-PLA2 mass and activity were measured in 2587 patients in the Myocardial Ischemia Reduction With Acute Cholesterol Lowering (MIRACL) trial at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. Baseline levels of sPLA2 and Lp-PLA2 mass and activity were not associated with the primary efficacy measure of the trial of death, myocardial infarction, or unstable angina. However, in the overall cohort, baseline sPLA2 mass predicted risk of death after multivariable adjustment (hazard ratio for 2-fold increase, 1.30; 95% confidence interval, 1.09–1.56;P =0.004). This association remained significant when examined separately in the placebo group but not in the atorvastatin group. Compared with placebo, atorvastatin reduced median sPLA2 mass (−32.1% versus −23.1%), sPLA2 activity (−29.5% versus −19.2%), Lp-PLA2 mass (−35.8% versus −6.2%), and Lp-PLA2 activity (−24.3% versus 5.4%;P <0.001 for all). Atorvastatin reduced the hazard of death associated with elevated sPLA2 mass and activity by ≈50%.Conclusions— sPLA2 mass independently predicts death during a 16-week period after acute coronary syndrome. High-dose atorvastatin significantly reduces sPLA2 and Lp-PLA2 mass and activity after acute coronary syndrome and mitigates the risk of death associated with sPLA2 mass. Atorvastatin may exert antiinflammatory effects on phospholipases that contribute to its therapeutic benefit after acute coronary syndrome.