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

Thompson, A. et al. (2010) Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet, 375(9725), pp. 1536-1544. (doi: 10.1016/S0140-6736(10)60319-4)

Abstract

<b>Background</b>: 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. <b>Methods</b>: 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. <b>Findings</b>: 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. <b>Interpretation</b>: 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

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Caslake, Professor Muriel and Packard, Professor Chris
• Authors: Thompson, A., Gao, P., Orfei, L., Ballantyne, C., Cannon, C.P., Criqui, M., Cushman, M., Hofman, A., Packard, C., Thompson, S.G., Danesh, J., and Caslake, M.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Lancet
• Publisher: The Lancet Publishing Group
• ISSN: 0140-6736
• ISSN (Online): 1474-547X