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Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies.
Tuesday,2012-11-06 12:03 America/Los_Angeles — eenright
| Title | Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | Thompson, A, Gao, P, Orfei, L, Watson, S, Di Angelantonio, E, Kaptoge, S, Ballantyne, C, Cannon, CP, Criqui, M, Cushman, M, Hofman, A, Packard, C, Thompson, SG, Collins, R, Danesh, J |
| Corporate/Institutional Authors | Lp-PLA(2) Studies Collaboration, |
| Journal | Lancet |
| Volume | 375 |
| Issue | 9725 |
| Pagination | 1536-44 |
| Date Published | 2010 May 01 |
| ISSN | 1474-547X |
| 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 |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><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-PLA(2) or other risk factor. The primary outcome was coronary heart disease.</p><p><b>FINDINGS: </b>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.</p><p><b>INTERPRETATION: </b>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.</p><p><b>FUNDING: </b>UK Medical Research Council, GlaxoSmithKline, and British Heart Foundation.</p> |
| DOI | 10.1016/S0140-6736(10)60319-4 |
| Alternate Journal | Lancet |
| PubMed ID | 20435228 |
| PubMed Central ID | PMC2864403 |
| Grant List | MC_U137686851 / / Medical Research Council / United Kingdom G0601284 / / Medical Research Council / United Kingdom RG/08/008/25291 / / British Heart Foundation / United Kingdom G0600705 / / Medical Research Council / United Kingdom RG/08/014/24067 / / British Heart Foundation / United Kingdom G0401527 / / Medical Research Council / United Kingdom RG/08/014 / / British Heart Foundation / United Kingdom MC_U105260792 / / Medical Research Council / United Kingdom G0801566 / / Medical Research Council / United Kingdom / / Wellcome Trust / United Kingdom MC_U137686853 / / Medical Research Council / United Kingdom |