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Thompson, A.* ; Gao, P.* ; Orfei, L.* ; Watson, S.* ; di Angelantonio, E.* ; Kaptoge, S.* ; Ballantyne, C.* ; Cannon, C.P.* ; Criqui, M.* ; Cushman, M.* ; Hofman, A.* ; Packard, C.* ; Thompson, S.G.* ; Collins, R.* ; Danesh, J.* ; Willeit, J.* ; Kiechl, S.* ; Wiedemann, C.* ; Psaty, B.* ; Furberg, C.* ; Khaw, K.T.* ; Sandhu, M.* ; Benjamin, E.J.* ; Vasan, R.S.* ; Schnabel, R.B.* ; Oldgren, J.* ; Rossi, G.P.* ; Cesari, M.* ; Lenzini, L.* ; Zanchetta, M.* ; James, S.K.* ; Rimm, E.* ; Hatoum, I.* ; Anderson, J.L.* ; May, H.T.* ; Home, B.D.* ; Carlquist, J.F.* ; Muhlestein, J.B.* ; Koenig, W.* ; Brenner, H.* ; Rothenbacher, D.* ; Marz, W.* ; Bohm, B.* ; Winkelmann, B.R.* ; Winkler, K.* ; Berglund, G.* ; Persson, M.* ; Roger, V.* ; Gerber, Y.* ; Berger, P.B.* ; Brilakis, E.S.* ; McConnell, J.P.* ; Meisinger, C. ; Sacco, R.* ; Elkind, M.* ; Talmud, P.J.* ; O'Donoghue, M.* ; Sabatine, M.S.* ; Morrow, D.A.* ; Caslake, M.* ; Braunwald, E.* ; Barrett-Connor, E.* ; Daniels, L.B.* ; Laughlin, G.A.* ; Kardys, I.* ; Witteman, J.C.M.* ; Corsetti, J.P.* ; Rainwater, D.L.* ; Moss, A.J.* ; Wassertheil-Smoller, S.* ; Ridker, P.* ; Nelson, J.J.* ; Zariffa, N.* ; Zalewski, A.* ; Walker, M.*

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

Lancet 375, 1536-1544 (2010)
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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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Activating-factor acetylhydrolase; Individual participant metaanalysis; Low-density-lipoprotein; Cardiovascular-disaese; Plasma-fibrinogen; Heart-disease; Myocardial-infarction; Regression dilution; Atherosclerosis; Lysophosphatidylcholine
ISSN (print) / ISBN 0140-6736
e-ISSN 0099-5355
Zeitschrift Lancet, The
Quellenangaben Band: 375, Heft: 9725, Seiten: 1536-1544 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed