Lipoprotein-associated phospholipase A(2) as an independent predictor of coronary heart disease.

Background: Chronic inflammation is believed to increase the risk of corona ry events by making atherosclerotic plaques in coronary vessels prone to ru pture. We examined blood constituents potentially affected by inflammation as predictors of risk in men with hypercholesterolemia who were enrolled in the West of Scotland Coronary Prevention Study, a trial that evaluated the value of pravastatin in the prevention of coronary events. Methods: A total of 580 men who had had a coronary event (nonfatal myocardi al infarction, death from coronary heart disease, or a revascularization pr ocedure) were each matched for age and smoking status with 2 control subjec ts (total, 1160) from the same cohort who had not had a coronary event. Lip oprotein-associated phospholipase A(2), C-reactive protein, and fibrinogen levels and the white-cell count were measured at base line, along with othe r traditional risk factors. The association of these variables with the ris k of coronary events was tested in regression models and by dividing the ra nge of values according to quintiles. Results: Levels of C-reactive protein, the white-cell count, and fibrinogen levels were strong predictors of the risk of coronary events; the risk in the highest quintile of the study cohort for each variable was approximatel y twice that in the lowest quintile. However, the association of these vari ables with risk was markedly attenuated when age, systolic blood pressure, and lipoprotein levels were included in multivariate models. Levels of lipo protein-associated phospholipase A(2) (platelet-activating factor acetylhyd rolase), the expression of which is regulated by mediators of inflammation, had a strong, positive association with risk that was not confounded by ot her factors. It was associated with almost a doubling of the risk in the hi ghest quintile as compared with the lowest quintile. Conclusions: Inflammatory markers are predictors of the risk of coronary ev ents, but their predictive ability is attenuated by associations with other coronary risk factors. Elevated levels of lipoprotein-associated phospholi pase A(2) appear to be a strong risk factor for coronary heart disease, a f inding that has implications for atherogenesis and the assessment of risk. (N Engl J Med 2000;343:1148-55.) (C) 2000 Massachusetts Medical Society.