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-PLA2mass 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-PLA2or other risk factor. The primary outcome was coronary heart disease. Findings: Lp-PLA2activity 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-PLA2activity 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-PLA2activity and 1·11 (1·07-1·16) with Lp-PLA2mass 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-PLA2did not differ significantly in people with and without initial stable vascular disease, apart from for vascular death with Lp-PLA2mass. 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-PLA2activity 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-PLA2mass and activity are not exclusive to vascular outcomes, and the vascular associations depend at least partly on lipids. Funding: UK Medical Research Council, GlaxoSmithKline, and British Heart Foundation.

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