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

Thompson, Alexander ; Gao, Pei ; Orfei, Lia ; Watson, Sarah ; Di Angelantonio, Emanuele ; Kaptoge, Stephen ; Ballantyne, Christie ; Cannon, Christopher P. ; Criqui, Michael and Cushman, Mary , et al. (2010) In The Lancet 375(9725). p.1536-1544
Abstract

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-PLA2 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-PLA2 or other risk factor. The primary outcome... (More)

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-PLA2 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-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 differsignificantly 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.

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Danesh, John ; Willeit, Johann ; Kiechl, Stefan ; Wiedermann, Christian ; Psaty, Bruce ; Furberg, Curt ; Khaw, Kay Tee ; Sandhu, Manjinder ; Benjamin, Emelia J. ; Vasan, Ramachandran S. ; Schnabel, Renate B. ; Oldgren, Jonas ; Rossi, Gian Paolo ; Cesari, Maurizio ; Lenzini, Livia ; Zanchetta, Mario ; James, Stefan K. ; Rimm, Eric ; Hatoum, Ida ; Anderson, Jeffrey L. ; May, Heidi T. ; Horne, Benjamin D. ; Carlquist, John F. ; Muhlestein, Joseph B. ; Koenig, Wolfgang ; Brenner, Hermann ; Rothenbacher, Dietrich ; März, Winfried ; Böhm, Bernhard ; Winkelmann, Bernhard R. ; Winkler, Karl ; LU ; LU ; Roger, Veronique ; Gerber, Yariv and Berger, Peter B.
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published
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The Lancet
volume
375
issue
9725
pages
9 pages
publisher
Elsevier Limited
external identifiers
  • pmid:20435228
  • scopus:77951605907
ISSN
0140-6736
DOI
10.1016/S0140-6736(10)60319-4
language
English
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no
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50ad1f7d-b6de-476e-bc06-07eddd77bb03
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2019-06-24 09:39:42
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2020-02-26 07:30:08
@article{50ad1f7d-b6de-476e-bc06-07eddd77bb03,
  abstract     = {<p>Background Lipoprotein-associated phospholipase A<sub>2</sub> (Lp-PLA<sub>2</sub>), 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<sub>2</sub> 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<sub>2</sub> or other risk factor. The primary outcome was coronary heart disease. Findings Lp-PLA<sub>2</sub> 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<sub>2</sub> 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<sub>2</sub> activity and 1·11 (1·07-1·16) with Lp-PLA<sub>2</sub> 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<sub>2</sub> did not differsignificantly in people with and without initial stable vascular disease, apart from for vascular death with Lp-PLA<sub>2</sub> 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<sub>2</sub> 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<sub>2</sub> mass and activity are not exclusive to vascular outcomes, and the vascular associations depend at least partly on lipids.</p>},
  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},
  issn         = {0140-6736},
  language     = {eng},
  month        = {01},
  number       = {9725},
  pages        = {1536--1544},
  publisher    = {Elsevier Limited},
  series       = {The Lancet},
  title        = {Lipoprotein-associated phospholipase A<sub>2</sub> and risk of coronary disease, stroke, and mortality : Collaborative analysis of 32 prospective studies},
  url          = {http://dx.doi.org/10.1016/S0140-6736(10)60319-4},
  doi          = {10.1016/S0140-6736(10)60319-4},
  volume       = {375},
  year         = {2010},
}