Thompson, A and Gao, P and Orfei, L and Watson, S and Di Angelantonio, E and Kaptoge, S and Ballantyne, C and Cannon, CP and Criqui, M and Cushman, M and Hofman, A and Packard, C and Thompson, SG and Collins, R and Danesh, J and Ballantyne, C and Willeit, J and Kiechl, S and Wiedemann, C and Cushman, M and Psaty, B and Furberg, C and Khaw, KT and Sandhu, M and Benjamin, EJ and Vasan, RS and Schnabel, RB and Oldgren, J and Rossi, GP and Cesari, M and Lenzini, L and Zanchetta, M and James, SK and Rimm, E and Hatoum, I and Collins, R and Anderson, JL and May, HT and Home, BD and Carlquist, JF and Muhlestein, JB and Koenig, W and Brenner, H and Rothenbacher, D and Marz, W and Bohm, B and Winkelmann, BR and Winkler, K and Berglund, G and Persson, M and Roger, V and Gerber, Y and Berger, PB and Brilakis, ES and McConnell, JP and Koenig, W and Meisinger, C and Rimm, E and Hatoum, I and Sacco, R and Elkind, M and Talmud, PJ and O'Donoghue, M and Sabatine, MS and Morrow, DA and Packard, C and Caslake, M and Braunwald, E and Cannon, CP and Barrett-Connor, E and Daniels, LB and Laughlin, GA and Hofman, A and Kardys, I and Witteman, JCM and Criqui, M and Corsetti, JP and Rainwater, DL and Moss, AJ and Wassertheil-Smoller, S and Ridker, P and Packard, C and Ballantyne, C and Cannon, CP and Collins, R and Criqui, M and Cushman, M and Danesh, J and Hofman, A and Nelson, JJ and Packard, C and Thompson, SG and Zariffa, N and Zalewski, A and Watson, S and Walker, M and Lp-PLA2 Studies Collaboration, (2010) Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. LANCET , 375 (9725) 1536 - 1544.
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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.
|Title:||Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies|
|Keywords:||ACTIVATING-FACTOR ACETYLHYDROLASE, INDIVIDUAL PARTICIPANT METAANALYSIS, LOW-DENSITY-LIPOPROTEIN, CARDIOVASCULAR-DISEASE, PLASMA-FIBRINOGEN, HEART-DISEASE, MYOCARDIAL-INFARCTION, REGRESSION DILUTION, ATHEROSCLEROSIS, LYSOPHOSPHATIDYLCHOLINE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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