Open AccessChanges 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
Author(s) -
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
Publication year - 2013
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.113.000360
Subject(s) - pravastatin , medicine , myocardial infarction , placebo , cardiology , lipoprotein associated phospholipase a2 , statin , hazard ratio , cholesterol , lipoprotein , endocrinology , confidence interval , alternative medicine , pathology
Background Lipoprotein‐associated phospholipase A2 (Lp‐ PLA 2 ) levels are associated with coronary heart disease ( CHD ) in healthy individuals and in patients who have had ischemic events. Methods and Results 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‐ PLA 2 activity to predict outcomes over a 6‐year follow‐up, the effect of pravastatin on Lp‐ PLA 2 levels, and whether pravastatin treatment effect was related to Lp‐ PLA 2 activity change. Lp‐ PLA 2 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‐ PLA 2 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‐ PLA 2 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‐ PLA 2 by 16% compared with placebo ( P <0.001). After adjustment for Lp‐ PLA 2 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‐ PLA 2 . Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change. Conclusion Reduction in Lp‐ PLA 2 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.