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.