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

Ford, I. , Robertson, M., Shepherd, J. and Cobbe, S. (2010) Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet, 375(9726), pp. 1634-1639. (doi: 10.1016/S0140-6736(10)60545-4)

Abstract

<p><b>Background</b> <br>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.</br></p> <p><b>Methods</b> <br>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.</br></p> <p><b>Findings</b> <br>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=4·4×10−24). The odds ratio for coronary heart disease was 1·18 (95% CI 1·11—1·26; p=2·6×10−7) 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=9·3×10−8) and smaller HDL particle size (0·14 nm [0·08—0·20]; p=7·0×10−5), factors that could mediate the effects of triglyceride.</br></p> <p><b>Interpretation</b> <br>These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease.</br></p> <p><b>Funding</b> <br>British Heart Foundation, UK Medical Research Council, Novartis.</br></p>

• Item Type: Articles (Editorial)
• Additional Information: <p>Glasgow authors part of <b>Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration</b></p> <p><b>Contributors</b> <br>Nadeem Sarwar and John Danesh drafted the report. Nadeem Sarwar, Adam S Butterworth, and Emanuele Di Angelantonio did the analyses. All members of the writing committee provided critical revisions. All investigators shared data and had opportunities to contribute to the interpretation of the results and critical revision of the report. The data management team undertook data collation and harmonisation. All members of the coordinating centre contributed to the collection, harmonisation, analysis, and interpretation of the data.</br></p> <p><b>Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration</b> <br><i>Writing committee</i> Nadeem Sarwar, University of Cambridge, Cambridge UK; Manjinder S Sandhu, University of Cambridge, Cambridge, UK; Sally L Ricketts, University of Cambridge, Cambridge, UK; Adam S Butterworth, University of Cambridge, Cambridge, UK; Emanuele Di Angelantonio, University of Cambridge, Cambridge, UK; S Matthijs Boekholdt, Academic Medical Center, Amsterdam, Netherlands; Willem Ouwehand, University of Cambridge, Cambridge, UK; Hugh Watkins, University of Oxford, Oxford, UK; Nilesh J Samani, University of Leicester, Leicester, UK; Danish Saleheen, University of Cambridge, Cambridge, UK; Debbie Lawlor, University of Bristol, Bristol, UK; Muredach P Reilly, University of Pennsylvania, Philadelphia, PA, USA; Aroon D Hingorani, University College London, London, UK; Philippa J Talmud, University College London, London, UK; John Danesh, University of Cambridge, Cambridge, UK.</br> <br><i>Triglyceride Coronary Disease Genetics Consortium investigators: BHF Family Study</i> P S Braund, A S Hall, N J Samani, J Thompson; Bloodomics W März, W Ouwehand, S Sivapalaratnam, N Soranzo, M Trip; BWHHS D A Lawlor, J P Casas, S Ebrahim; EPIC-Norfolk B J Arsenault, S M Boekholdt, K T Khaw, S L Ricketts, M S Sandhu, N J Wareham; KORA H Grallert, T Illig; NPHSII S E Humphries, P J Talmud; PENNCATH D J Rader, J He, M P Reilly; PROCARDIS R Clarke, A Hamsten, J C Hopewell, H Watkins; PROMIS D Saleheen, P Frossard, P Deloukas, J Danesh; SAS S Ye, I A Simpson; TARFS A Onat, E Kömürcü-Bayrak; Verona Heart Study N Martinelli, O Olivieri, D Girelli; WHITE II A D Hingorani, M Kivimäki, M Kumari; other studies B E Aouizerat, L Baum, H Campos, R Chaaba, B S Chen, E Y Cho, D Evans, J Hill, L A Hsu, J A Hubacek, CQ Lai, J H Lee, K Klos, H Liu, L Masana, B Melegh, T Nabika, J Ribalta, E Ruiz-Narvaez, G N Thomas, B Tomlinson, C Szalai, H Vaverkova, Y Yamada, Y Yang.</br> <br><i>Emerging Risk Factors Collaboration investigators</i>: AFTCAPS R W Tipping; ALLHAT C E Ford, S L Pressel; ARIC C Ballantyne, A Brautbar; BHS M Knuiman; BRHS P H Whincup, S G Wannamethee, R W Morris; BRUN S Kiechl, J Willeit, P Santer, A Mayr; BUPA N Wald; BWHHS S Ebrahim, D A Lawlor; CaPS J W G Yarnell, J Gallacher; CASTEL E Casiglia, V Tikhonoff; CHS M Cushman, B M Psaty, R P Tracy (see http://www.chs-nhlbi.org for acknowledgments); COPEN A Tybjærg-Hansen, B G Nordestgaard, M Benn, R Frikke-Schmidt; CUORE S Giampaoli, L Palmieri, S Panico, D Vanuzzo, L Pilotto; DRECE A Gómez de la Cámara, J A Gómez-Gerique; DUBBO L Simons, J McCallum, Y Friedlander; EAS FGR Fowkes, A J Lee; EPESEBOS J Taylor, J M Guralnik, C L Phillips; EPESEIOW R Wallace, J M Guralnik, C L Phillips; EPESENCA D G Blazer, J M Guralnik, C L Phillips; EPESENHA J M Guralnik, C L Phillips; EPICNOR K-T Khaw; ESTHER H Brenner, E Raum, H Müller, D Rothenbacher; FIA J H Jansson, P Wennberg; FINE-FIN A Nissinen; FINE-IT C Donfrancesco, S Giampaoli; FINRISK-92, FINRISK-97 V Salomaa, K Harald, P Jousilahti, E Vartiainen; FRAMOFF R B D'Agostino, R S Vasan, M J Pencina; GLOSTRUP E M Bladbjerg, T Jørgensen, L Møller, J Jespersen; GOH R Dankner, A Chetrit, F Lubin; GOTOW C Björkelund, L Lissner, C Bengtsson; GRIPS P Cremer, D Nagel; HONOL B Rodriguez; HOORN J M Dekker, G Nijpels, C D A Stehouwer; IKNS S Sato, H Iso, A Kitamura, H Noda; KIHD J T Salonen, K Nyyssönen, T-P Tuomainen, S Voutilainen; LEADER T W Meade, J A Cooper; MRFIT L H Kuller, G Grandits; NHANES III R Gillum, M Mussolino; NHS E Rimm, S Hankinson, J A E Manson, J K Pai; NPHS II J A Cooper, K A Bauer; OSAKA S Sato, A Kitamura, Y Naito, H Iso; PRIME P Amouyel, D Arveiler, A Evans, J Ferrières; PROCAM H Schulte, G Assmann; PROSPER C J Packard, N Sattar, R G Westendorp, B M Buckley; QUEBEC B Cantin, B Lamarche, J-P Després, G R Dagenais; RANCHO E Barrett-Connor, D L Wingard, R Bettencourt; REYK V Gudnason, T Aspelund, G Sigurdsson, B Thorsson; RIFLE M Trevisan; SHHEC H Tunstall-Pedoe, R Tavendale, G D O Lowe, M Woodward; SHS B V Howard, Y Zhang, L Best, J Umans; SPEED Y Ben-Shlomo, G Davey-Smith; TARFS A Onat; TROMSØ I Njølstad, E B Mathiesen, M L Løchen, T Wilsgaard; ULSAM E Ingelsson, L Lind, V Giedraitis, K Michaëlsson; WHITE II E Brunner, M Shipley; WHS P Ridker, J Buring; WOSCOPS J Shepherd, S M Cobbe, I Ford, M Robertson; ZARAGOZA A Marin Ibañez; ZUTE E J M Feskens, D Kromhout.</br> <br><i>Data management team</i> M Walker, S Watson.</br> <br><i>Coordinating centre</i> R Collins, E Di Angelantonio, S Kaptoge, PL Perry, N Sarwar, A Thompson, S G Thompson, M Walker, S Watson, I R White, A M Wood, J Danesh.</br></p>
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Robertson, Mrs Michele and Shepherd, Prof James and Ford, Professor Ian and Cobbe, Professor Stuart
• Authors: Ford, I., Robertson, M., Shepherd, J., and Cobbe, S.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre; ?? 20206000 ??
• Research Group: Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration
• Journal Name: Lancet
• Publisher: The Lancet Publishing Group
• ISSN: 0140-6736
• ISSN (Online): 1474-547X
• Published Online: 07 May 2010

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