Format

Send to:

Choose Destination
See comment in PubMed Commons below
Lancet. 2010 May 8;375(9726):1634-9. doi: 10.1016/S0140-6736(10)60545-4.

Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies.

Collaborators (242)

Braund PS, Hall AS, Samani NJ, Thompson J, März W, Ouwehand W, Sivapalaratnam S, Soranzo N, Trip M, Lawlor DA, Casas JP, Ebrahim S, Arsenault BJ, Boekholdt SM, Khaw KT, Ricketts SL, Sandhu MS, Wareham NJ, Grallert H, Illig T, Humphries SE, Talmud T, Rader DJ, He J, Reilly MP, Clarke R, Hamsten A, Hopewell JC, Watkins H, Saleheen D, Frossard P, Deloukas P, Danesh J, Ye S, Simpson IA, Onat A, Kömürcü-Bayrak E, Martinelli N, Olivieri O, Girelli D, Hingorani AD, Kivimäki M, Kumari M, Aouizerat BE, Baum L, Campos H, Chaaba R, Chen BS, Cho EY, Evans D, Hill J, Hsu LA, Hubacek JA, Lai CQ, Lee JH, Klos K, Liu H, Masana L, Melegh B, Nabika T, Ribalta J, Ruiz-Narvaez E, Thomas GN, Tomlinson B, Szalai C, Vaverkova H, Yamada Y, Yang Y, Kastelein JJ, Tipping RW, Ford CE, Pressel SL, Ballantyne C, Brautbar A, Knuiman M, Whincup PH, Wannamethee SG, Morris RW, Kiechl S, Willeit J, Santer P, Mayr A, Wald N, Ebrahim S, Lawlor DA, Yarnell JW, Gallacher J, Casiglia E, Tikhonoff V, Cushman M, Psaty BM, Tracy RP, Tybjaerg-Hansen A, Nordestgaard BG, Benn M, Frikke-Schmidt R, Giampaoli S, Palmieri L, Panico S, Vanuzzo D, Pilotto L, de la Cámara AG, Gómez-Gerique JA, Simons L, McCallum J, Friedlander Y, Fowkes FG, Lee AJ, Taylor J, Guralnik JM, Phillips CL, Wallace R, Guralnik JM, Phillips CL, Blazer DG, Guralnik JM, Phillips CL, Guralnik JM, Phillips CL, Khaw KT, Brenner H, Raum E, Müller H, Rothenbacher D, Jansson JH, Wennberg P, Nissinen A, Donfrancesco C, Giampaoli S, Salomaa V, Harald K, Jousilahti P, Vartiainen E, D'Agostino RB, Vasan RS, Pencina MJ, Bladbjerg EM, Jørgensen T, Møller L, Jespersen J, Dankner R, Chetrit A, Lubin F, Björkelund C, Lissner L, Bengtsson C, Cremer P, Nagel D, Rodriguez B, Dekker JM, Nijpels G, Stehouwer CD, Sato S, Iso H, Kitamura A, Noda H, Salonen JT, Nyyssönen K, Tuomainen TP, Voutilainen S, Meade TW, Cooper JA, Kuller LH, Grandits G, Gillum R, Mussolino M, Rimm E, Hankinson S, Manson JA, Pai JK, Cooper JA, Bauer KA, Sato S, Kitamura A, Naito Y, Iso H, Amouyel P, Arveiler D, Evans A, Ferrières J, Schulte H, Assmann G, Packard CJ, Sattar N, Westendorp RG, Buckley BM, Cantin B, Lamarche B, Després JP, Dagenais GR, Barrett-Connor E, Wingard DL, Bettencourt R, Gudnason V, Aspelund T, Sigurdsson G, Thorsson B, Trevisan M, Tunstall-Pedoe H, Tavendale R, Lowe GD, Woodward M, Howard BV, Zhang Y, Best L, Umans J, Ben-Shlomo Y, Davey-Smith G, Onat A, Njølstad I, Mathiesen EB, Løchen ML, Wilsgaard T, Ingelsson E, Lind L, Giedraitis V, Michaëlsson K, Brunner E, Shipley M, Ridker P, Buring J, Shepherd J, Cobbe SM, Ford I, Robertson M, Ibañez AM, Feskens EJ, Kromhout D, Walker M, Watson S, Collins R, Di Angelantonio E, Kaptoge S, Perry PL, Sarwar N, Thompson A, Thompson SG, Walker M, Watson S, White IR, Wood AM, Danesh J.

Erratum in

  • Lancet. 2010 Jul 10;376(9735):90. Kastelein, J J [added].

Abstract

BACKGROUND:

Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality.

METHODS:

We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20,842 patients with coronary heart disease, 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12,785 incident cases of coronary heart disease during 2.79 million person-years at risk). We analysed -1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy.

FINDINGS:

The minor allele frequency of -1131T>C was 8% (95% CI 7-9). -1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3.5% [95% CI 2.6-4.6]; 0.053 mmol/L [0.039-0.068]), lower apolipoprotein AI (1.3% [0.3-2.3]; 0.023 g/L [0.005-0.041]), and higher apolipoprotein B (3.2% [1.3-5.1]; 0.027 g/L [0.011-0.043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% (95% CI 12.9-18.7), or 0.25 mmol/L (0.20-0.29), higher (p=4.4x10(-24)). The odds ratio for coronary heart disease was 1.18 (95% CI 1.11-1.26; p=2.6x10(-7)) per C allele, which was concordant with the hazard ratio of 1.10 (95% CI 1.08-1.12) per 16% higher triglyceride concentration recorded in prospective studies. -1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12.2 nmol/L [95% CI 7.7-16.7]; p=9.3x10(-8)) and smaller HDL particle size (0.14 nm [0.08-0.20]; p=7.0x10(-5)), factors that could mediate the effects of triglyceride.

INTERPRETATION:

These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease.

FUNDING:

British Heart Foundation, UK Medical Research Council, Novartis.

Copyright 2010 Elsevier Ltd. All rights reserved.

PMID:
20452521
[PubMed - indexed for MEDLINE]
PMCID:
PMC2867029
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk