Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality

Collaborative analysis of 32 prospective studies

The Lp-PLA Studies Collaboration

Research output: Contribution to journalArticle

437 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1536-1544
Number of pages9
JournalThe Lancet
Volume375
Issue number9725
DOIs
StatePublished - 2010

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1-Alkyl-2-acetylglycerophosphocholine Esterase
Coronary Disease
Stroke
Prospective Studies
Mortality
Blood Vessels
Odds Ratio
Blood Pressure
Vascular Diseases
Cholesterol
Lipids
Atherosclerotic Plaques
Lipoproteins
Meta-Analysis

ASJC Scopus subject areas

  • Medicine(all)

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Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality : Collaborative analysis of 32 prospective studies. / The Lp-PLA Studies Collaboration.

In: The Lancet, Vol. 375, No. 9725, 2010, p. 1536-1544.

Research output: Contribution to journalArticle

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title = "Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: Collaborative analysis of 32 prospective studies",
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 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.",
author = "{The Lp-PLA Studies Collaboration} and Alexander Thompson and Pei Gao and Lia Orfei and Sarah Watson and {Di Angelantonio}, Emanuele and Stephen Kaptoge and Christie Ballantyne and Cannon, {Christopher P.} and Michael Criqui and Mary Cushman and Albert Hofman and Chris Packard and Thompson, {Simon G.} and Rory Collins and John Danesh and Johann Willeit and Stefan Kiechl and Christian Wiedermann and Bruce Psaty and Curt Furberg and Khaw, {Kay Tee} and Manjinder Sandhu and Benjamin, {Emelia J.} and Vasan, {Ramachandran S.} and Schnabel, {Renate B.} and Jonas Oldgren and Rossi, {Gian Paolo} and Maurizio Cesari and Livia Lenzini and Mario Zanchetta and James, {Stefan K.} and Eric Rimm and Ida Hatoum and Anderson, {Jeffrey L.} and May, {Heidi T.} and Horne, {Benjamin D.} and Carlquist, {John F.} and Muhlestein, {Joseph B.} and Wolfgang Koenig and Hermann Brenner and Dietrich Rothenbacher and Winfried M{\"a}rz and Bernhard B{\"o}hm and Winkelmann, {Bernhard R.} and Karl Winkler and Goran Berglund and Margaretha Persson and Veronique Roger and Yariv Gerber and Brilakis, {Emmanouil S.}",
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TY - JOUR

T1 - Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality

T2 - Collaborative analysis of 32 prospective studies

AU - The Lp-PLA Studies Collaboration

AU - Thompson, Alexander

AU - Gao, Pei

AU - Orfei, Lia

AU - Watson, Sarah

AU - Di Angelantonio, Emanuele

AU - Kaptoge, Stephen

AU - Ballantyne, Christie

AU - Cannon, Christopher P.

AU - Criqui, Michael

AU - Cushman, Mary

AU - Hofman, Albert

AU - Packard, Chris

AU - Thompson, Simon G.

AU - Collins, Rory

AU - Danesh, John

AU - Willeit, Johann

AU - Kiechl, Stefan

AU - Wiedermann, Christian

AU - Psaty, Bruce

AU - Furberg, Curt

AU - Khaw, Kay Tee

AU - Sandhu, Manjinder

AU - Benjamin, Emelia J.

AU - Vasan, Ramachandran S.

AU - Schnabel, Renate B.

AU - Oldgren, Jonas

AU - Rossi, Gian Paolo

AU - Cesari, Maurizio

AU - Lenzini, Livia

AU - Zanchetta, Mario

AU - James, Stefan K.

AU - Rimm, Eric

AU - Hatoum, Ida

AU - Anderson, Jeffrey L.

AU - May, Heidi T.

AU - Horne, Benjamin D.

AU - Carlquist, John F.

AU - Muhlestein, Joseph B.

AU - Koenig, Wolfgang

AU - Brenner, Hermann

AU - Rothenbacher, Dietrich

AU - März, Winfried

AU - Böhm, Bernhard

AU - Winkelmann, Bernhard R.

AU - Winkler, Karl

AU - Berglund, Goran

AU - Persson, Margaretha

AU - Roger, Veronique

AU - Gerber, Yariv

AU - Brilakis, Emmanouil S.

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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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U2 - 10.1016/S0140-6736(10)60319-4

DO - 10.1016/S0140-6736(10)60319-4

M3 - Article

VL - 375

SP - 1536

EP - 1544

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9725

ER -