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

Nadeem Sarwar; Manjinder S Sandhu; Sally L. Ricketts; Adam S. Butterworth; Emanuele Di Angelantonio; S. Matthijs Boekholdt; Willem Ouwehand; Hugh Watkins; Nilesh J. Samani; Danish Saleheen; Debbie Lawlor; Muredach P. Reilly; Aroon D. Hingorani; Philippa J. Talmud; John Danesh; Karl Michaëlsson; Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration

doi:10.1016/S0140-6736(10)60545-4

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

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

Nadeem Sarwar, Manjinder S Sandhu, Sally L. Ricketts, Adam S. Butterworth, Emanuele Di Angelantonio, S. Matthijs Boekholdt, Willem Ouwehand, Hugh Watkins, Nilesh J. Samani, Danish Saleheen, …

The Lancet (British edition), Vol.375(9726), pp.1634-1639

2010

DOI: 10.1016/S0140-6736(10)60545-4

PMCID: PMC2867029

PMID: 20452521

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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=4·4×10 −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. 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.

Medical and Health Sciences

Medicin och hälsovetenskap

Details

Title: Subtitle: Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies
Creators: Nadeem Sarwar
Manjinder S Sandhu - University of Cambridge
Sally L. Ricketts
Adam S. Butterworth
Emanuele Di Angelantonio - University of Cambridge
S. Matthijs Boekholdt - University of Oxford
Willem Ouwehand - University of Cambridge
Hugh Watkins - University of Oxford
Nilesh J. Samani - University of Leicester
Danish Saleheen - University of Cambridge
Debbie Lawlor - University of Bristol
Muredach P. Reilly
Aroon D. Hingorani - University College London
Philippa J. Talmud - University College London
John Danesh - University of Cambridge
Karl Michaëlsson - Ortopedi
Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration
Contributors: R Wallace (Contributor) - University of Iowa, Internal Medicine
Resource Type: Journal article
Publication Details: The Lancet (British edition), Vol.375(9726), pp.1634-1639
DOI: 10.1016/S0140-6736(10)60545-4
PMID: 20452521
PMCID: PMC2867029
NLM abbreviation: Lancet
ISSN: 1474-547X
eISSN: 1474-547X
Grant note: DOI: 10.13039/501100000274, name: British Heart Foundation; DOI: 10.13039/100004336, name: Novartis; DOI: 10.13039/501100000265, name: Medical Research Council
Language: English
Date published: 2010
Academic Unit: Epidemiology; Injury Prevention Research Center; Internal Medicine
Record Identifier: 9984364404202771

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