Lipoprotein-associated phospholipase A₂ and risk of coronary disease, stroke, and mortality: Collaborative analysis of 32 prospective studies

Background Lipoprotein-associated phospholipase A₂ (Lp-PLA₂), an inflammatory enzyme expressed in atherosclerotic plaques, is a therapeutic target being assessed in trials of vascular disease prevention. We investigated associations of circulating Lp-PLA₂ mass and activity with risk of coronary heart disease, stroke, and mortality under different circumstances. Methods With use of individual records from 79 036 participants in 32 prospective studies (yielding 17 722 incident fatal or non-fatal outcomes during 474 976 person-years at risk), we did a meta-analysis of within-study regressions to calculate risk ratios (RRs) per 1 SD higher value of Lp-PLA₂ or other risk factor. The primary outcome was coronary heart disease. Findings Lp-PLA₂ activity and mass were associated with each other (r=0·51, 95% CI 0·47-0·56) and proatherogenic lipids. We noted roughly log-linear associations of Lp-PLA₂ activity and mass with risk of coronary heart disease and vascular death. RRs, adjusted for conventional risk factors, were: 1·10 (95% CI 1·05-1·16) with Lp-PLA₂ activity and 1·11 (1·07-1·16) with Lp-PLA₂ mass for coronary heart disease; 1·08 (0·97-1·20) and 1·14 (1·02-1·27) for ischaemic stroke; 1·16 (1·09-1·24) and 1·13 (1·05-1·22) for vascular mortality; and 1·10 (1·04-1·17) and 1·10 (1·03-1·18) for non-vascular mortality, respectively. RRs with Lp-PLA₂ did not differsignificantly in people with and without initial stable vascular disease, apart from for vascular death with Lp-PLA₂ mass. Adjusted RRs for coronary heart disease were 1·10 (1·02-1·18) with non-HDL cholesterol and 1·10 (1·00-1·21) with systolic blood pressure. Interpretation Lp-PLA₂ activity and mass each show continuous associations with risk of coronary heart disease, similar in magnitude to that with non-HDL cholesterol or systolic blood pressure in this population. Associations of Lp-PLA₂ mass and activity are not exclusive to vascular outcomes, and the vascular associations depend at least partly on lipids.