Phospholipase A2 Enzymes, High-Dose Atorvastatin, and Prediction of Ischemic Events Following Acute Coronary Syndromes
Background—Secretory (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 to placebo in patients with acute coronary syndrome (ACS) 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/day or placebo. Baseline levels of sPLA2 and Lp-PLA2 mass and activity were not associated with the trial's primary efficacy measure 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 (95%CI) 1.30 (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 vs. -23.1%), sPLA2 activity (-29.5 vs. -19.2%), Lp-PLA2 mass (-35.8 vs. -6.2%), and Lp-PLA2 activity (-24.3 vs. 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 following ACS. High dose atorvastatin significantly reduces sPLA2 and Lp-PLA2 mass and activity after ACS and mitigates the risk of death associated with sPLA2 mass. Atorvastatin may exert anti-inflammatory effects on phospholipases that contribute to its therapeutic benefit after ACS.
- Received August 19, 2011.
- Accepted December 16, 2011.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited