Article ; Online: Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies.
2010 Volume 375, Issue 9725, Page(s) 1536–1544
Abstract: ... of coronary heart disease, stroke, and mortality under different circumstances.: Methods: With use of individual records ... activity and mass each show continuous associations with risk of coronary heart disease, similar ... coronary heart disease.: Findings: Lp-PLA(2) activity and mass were associated with each other (r=0.51, 95% CI 0.47-0 ...
| 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. |
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| MeSH term(s) | 1-Alkyl-2-acetylglycerophosphocholine Esterase/blood ; Blood Pressure ; Coronary Disease/blood ; Coronary Disease/mortality ; Female ; Humans ; Linear Models ; Lipids/blood ; Male ; Middle Aged ; Prospective Studies ; Risk Assessment ; Risk Factors ; Stroke/blood ; Systole | ||||||||||
| Chemical Substances | Lipids ; 1-Alkyl-2-acetylglycerophosphocholine Esterase (EC 3.1.1.47) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2010-05-08 | ||||||||||
| Publishing country | England | ||||||||||
| Document type | Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 3306-6 | ||||||||||
| ISSN | 1474-547X ; 0023-7507 ; 0140-6736 | ||||||||||
| ISSN (online) | 1474-547X | ||||||||||
| ISSN | 0023-7507 ; 0140-6736 | ||||||||||
| DOI | 10.1016/S0140-6736(10)60319-4 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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