Phospholipase A(2) Enzymes, High-Dose Atorvastatin, and Prediction of Ischemic Events After Acute Coronary Syndromes
2012 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 6, 757-U71 p.Article in journal (Refereed) Published
Background-Secretory phospholipase A2 (sPLA(2)) and lipoprotein-associated phospholipase A2 (Lp-PLA(2)) 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. less thanbrgreater than less thanbrgreater thanMethods and Results-sPLA(2) and Lp-PLA(2) 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 sPLA(2) and Lp-PLA(2) 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 sPLA(2) 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 sPLA(2) mass (-32.1% versus -23.1%), sPLA(2) activity (-29.5% versus -19.2%), Lp-PLA(2) mass (-35.8% versus -6.2%), and Lp-PLA(2) activity (-24.3% versus 5.4%; P andlt; 0.001 for all). Atorvastatin reduced the hazard of death associated with elevated sPLA(2) mass and activity by approximate to 50%. less thanbrgreater than less thanbrgreater thanConclusions-sPLA(2) mass independently predicts death during a 16-week period after acute coronary syndrome. High-dose atorvastatin significantly reduces sPLA(2) and Lp-PLA(2) mass and activity after acute coronary syndrome and mitigates the risk of death associated with sPLA(2) mass. Atorvastatin may exert antiinflammatory effects on phospholipases that contribute to its therapeutic benefit after acute coronary syndrome.
Place, publisher, year, edition, pages
American Heart Association , 2012. Vol. 125, no 6, 757-U71 p.
acute coronary syndrome, hydroxymethylglutaryl-CoA reductase inhibitors, lipoproteins, phospholipases, oxidation-reduction
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-75900DOI: 10.1161/CIRCULATIONAHA.111.063487ISI: 000300605200013OAI: oai:DiVA.org:liu-75900DiVA: diva2:510550
Funding Agencies|Fondation Leducq||Pfizer, Inc.||General Clinical Research Center, University of California, San Diego||National Center for Research Resources, USPHS|M01RR00827|Pfizer||Anthera Pharmaceuticals||Karobio||Merck||Roche||AstraZeneca||2012-03-162012-03-162012-03-16