Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study

• Published in: Journal of the American Heart Association Vol. 2; no. 5; p. e000360
• Main Authors: White, Harvey D, Simes, John, Stewart, Ralph A H, Blankenberg, Stefan, Barnes, Elizabeth H, Marschner, Ian C, Thompson, Peter, West, Malcolm, Zeller, Tanja, Colquhoun, David M, Nestel, Paul, Keech, Anthony C, Sullivan, David R, Hunt, David, Tonkin, Andrew
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 14.12.2013
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine Esterase - blood; 1-Alkyl-2-acetylglycerophosphocholine Esterase - drug effects; Adult; Aged; Anticholesteremic Agents - pharmacology; Anticholesteremic Agents - therapeutic use; Coronary Disease - blood; Coronary Disease - prevention & control; Double-Blind Method; Female; Humans; Male; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - prevention & control; Myocardial Ischemia - blood; Myocardial Ischemia - drug therapy; Original Research; Pravastatin - pharmacology; Pravastatin - therapeutic use; Predictive Value of Tests; Time Factors; Lp‐PLA2; biomarkers; pravastatin; LIPID
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.113.000360

Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with coronary heart disease (CHD) in healthy individuals and in patients who have had ischemic events. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study randomized 9014 patients with cholesterol levels of 4.0 to 7.0 mmol/L to placebo or pravastatin 3 to 36 months after myocardial infarction or unstable angina and showed a reduction in CHD and total mortality. We assessed the value of baseline and change in Lp-PLA2 activity to predict outcomes over a 6-year follow-up, the effect of pravastatin on Lp-PLA2 levels, and whether pravastatin treatment effect was related to Lp-PLA2 activity change. Lp-PLA2 was measured at randomization and 1 year, and levels were grouped as quartiles. The prespecified end point was CHD death or nonfatal myocardial infarction. Baseline Lp-PLA2 activity was positively associated with CHD events (P < 0.001) but not after adjustment for 23 baseline factors (P = 0.66). In 6518 patients who were event free at 1 year, change in Lp-PLA2 was a significant independent predictor of subsequent CHD events after adjustment for these risk factors, including LDL cholesterol and LDL cholesterol changes (P < 0.001). Pravastatin reduced Lp-PLA2 by 16% compared with placebo (P < 0.001). After adjustment for Lp-PLA2 change, the pravastatin treatment effect was reduced from 23% to 10% (P = 0.26), with 59% of the treatment effect accounted for by changes in Lp-PLA2. Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change. Reduction in Lp-PLA2 activity during the first year was a highly significant predictor of CHD events, independent of change in LDL cholesterol, and may account for over half of the benefits of pravastatin in the LIPID study.