@article {583, title = {Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies.}, journal = {Lancet}, volume = {375}, year = {2010}, month = {2010 May 01}, pages = {1536-44}, abstract = {

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), 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-PLA(2) 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-PLA(2) or other risk factor. The primary outcome was coronary heart disease.

FINDINGS: Lp-PLA(2) 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-PLA(2) 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-PLA(2) activity and 1.11 (1.07-1.16) with Lp-PLA(2) 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-PLA(2) did not differ significantly in people with and without initial stable vascular disease, apart from for vascular death with Lp-PLA(2) 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-PLA(2) 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-PLA(2) mass 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.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Blood Pressure, Coronary Disease, Female, Humans, Linear Models, Lipids, Male, Middle Aged, Prospective Studies, Risk Assessment, Risk Factors, Stroke, Systole}, issn = {1474-547X}, doi = {10.1016/S0140-6736(10)60319-4}, author = {Thompson, Alexander and Gao, Pei and Orfei, Lia and Watson, Sarah and Di Angelantonio, Emanuele and Kaptoge, Stephen and Ballantyne, Christie and Cannon, Christopher P and Criqui, Michael and Cushman, Mary and Hofman, Albert and Packard, Chris and Thompson, Simon G and Collins, Rory and Danesh, John} }