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Saturday, May 01, 2010

Lipoprotein-associated phospholipase A2


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

The Lp-PLA2 Studies CollaborationCorresponding Author

Summary

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-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 differ significantly 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.

Funding

UK Medical Research Council, GlaxoSmithKline, and British Heart Foundation.
Corresponding Author Information Correspondence to: Lp-PLA2 Studies Collaboration Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK lsc@phpc.cam.ac.uk
 Members listed at end of paper

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