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

AUTHOR GROUP; W. Marz; R. Hamsten; J.A. Simpson; A. Onat; E. Komurcu-Bayrak; N. Martinelli; O. Olivieri; D. Girelli; M. Kivimaki; M. Kumari; 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; C.Q. Lai; J. H. van der 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; R.W. Tipping; C.E. Ford; S.L. Pressel; C. Ballantyne; A. Brautbar; M. Knuiman; P.H. Winchup; S.G. Wannamethee; R.W. Morris; S. Kiechl; J. Willeit; P. Santer; A. Mayr; N. Wald; J.M. Dekker; G. Nijpels; I.R. White; A.M. Wood

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

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

AUTHOR GROUP, W. Marz, R. Hamsten, J.A. Simpson, A. Onat, E. Komurcu-Bayrak, N. Martinelli, O. Olivieri, D. Girelli, M. Kivimaki, M. Kumari, B.E. Aouizerat, L. Baum, H. Campos, R. Chaaba, B.S. Chen, E.Y. Cho, D. Evans, J. Hill, L.A. HsuJ.A. Hubacek, C.Q. Lai, J. H. van der 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, R.W. Tipping, C.E. Ford, S.L. Pressel, C. Ballantyne, A. Brautbar, M. Knuiman, P.H. Winchup, S.G. Wannamethee, R.W. Morris, S. Kiechl, J. Willeit, P. Santer, A. Mayr, N. Wald, J.M. Dekker, G. Nijpels, I.R. White, A.M. Wood

Research output: Contribution to journal › Article › Academic › peer-review

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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=4.4x10(-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

Original language	English
Pages (from-to)	1634-1639
Journal	Lancet
Volume	375
Issue number	9726
DOIs	https://doi.org/10.1016/S0140-6736(10)60545-4
Publication status	Published - 2010

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

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AUTHOR GROUP, Marz, W., Hamsten, R., Simpson, J. A., Onat, A., Komurcu-Bayrak, E., Martinelli, N., Olivieri, O., Girelli, D., Kivimaki, M., Kumari, M., Aouizerat, B. E., Baum, L., Campos, H., Chaaba, R., Chen, B. S., Cho, E. Y., Evans, D., Hill, J., ... Wood, A. M. (2010). Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet, 375(9726), 1634-1639. https://doi.org/10.1016/S0140-6736(10)60545-4

@article{3ebe59a957724677982e668749d3ad7f,

title = "Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies",

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",

author = "Nadeem Sarwar and Sandhu, {Manjinder S.} and Ricketts, {Sally L.} and Butterworth, {Adam S.} and {Di Angelantonio}, Emanuele and Boekholdt, {S. Matthijs} and Willem Ouwehand and Hugh Watkins and Samani, {Nilesh J.} and Danish Saleheen and Debbie Lawlor and Reilly, {Muredach P.} and Hingorani, {Aroon D.} and Talmud, {Philippa J.} and John Danesh and {AUTHOR GROUP} and Braund, {P. S.} and Hall, {A. S.} and Samani, {N. J.} and J. Thompson and W. M{\"a}rz and W. Ouwehand and S. Sivapalaratnam and N. Soranzo and M. Trip and Lawlor, {D. A.} and Casas, {J. P.} and S. Ebrahim and Arsenault, {B. J.} and Khaw, {K. T.} and Ricketts, {S. L.} and Sandhu, {M. S.} and Wareham, {N. J.} and H. Grallert and T. Illig and Humphries, {S. E.} and Talmud Talmud and Rader, {D. J.} and J. He and Reilly, {M. P.} and R. Clarke and A. Hamsten and Hopewell, {J. C.} and H. Watkins and D. Saleheen and P. Frossard and P. Deloukas and J. Danesh and S. Ye and Simpson, {I. A.} and Kastelein, {J. J.} and W. Marz and R. Hamsten and J.A. Simpson and A. Onat and E. Komurcu-Bayrak and N. Martinelli and O. Olivieri and D. Girelli and M. Kivimaki and M. Kumari and B.E. Aouizerat and L. Baum and H. Campos and R. Chaaba and B.S. Chen and E.Y. Cho and D. Evans and J. Hill and L.A. Hsu and J.A. Hubacek and C.Q. Lai and {van der Lee}, {J. H.} and K. Klos and H. Liu and L. Masana and B. Melegh and T. Nabika and J. Ribalta and E. Ruiz-Narvaez and G.N. Thomas and B. Tomlinson and C. Szalai and H. Vaverkova and Y. Yamada and Y. Yang and R.W. Tipping and C.E. Ford and S.L. Pressel and C. Ballantyne and A. Brautbar and M. Knuiman and P.H. Winchup and S.G. Wannamethee and R.W. Morris and S. Kiechl and J. Willeit and P. Santer and A. Mayr and N. Wald and J.M. Dekker and G. Nijpels and I.R. White and A.M. Wood",

year = "2010",

doi = "https://doi.org/10.1016/S0140-6736(10)60545-4",

language = "English",

volume = "375",

pages = "1634--1639",

journal = "Lancet",

issn = "0140-6736",

publisher = "Elsevier Limited",

number = "9726",

}

AUTHOR GROUP, Marz, W, Hamsten, R, Simpson, JA, Onat, A, Komurcu-Bayrak, E, Martinelli, N, Olivieri, O, Girelli, D, Kivimaki, 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, van der 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, Tipping, RW, Ford, CE, Pressel, SL, Ballantyne, C, Brautbar, A, Knuiman, M, Winchup, PH, Wannamethee, SG, Morris, RW, Kiechl, S, Willeit, J, Santer, P, Mayr, A, Wald, N, Dekker, JM, Nijpels, G, White, IR & Wood, AM 2010, 'Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies', Lancet, vol. 375, no. 9726, pp. 1634-1639. https://doi.org/10.1016/S0140-6736(10)60545-4

TY - JOUR

T1 - Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

AU - Sarwar, Nadeem

AU - Sandhu, Manjinder S.

AU - Ricketts, Sally L.

AU - Butterworth, Adam S.

AU - Di Angelantonio, Emanuele

AU - Boekholdt, S. Matthijs

AU - Ouwehand, Willem

AU - Watkins, Hugh

AU - Samani, Nilesh J.

AU - Saleheen, Danish

AU - Lawlor, Debbie

AU - Reilly, Muredach P.

AU - Hingorani, Aroon D.

AU - Talmud, Philippa J.

AU - Danesh, John

AU - AUTHOR GROUP

AU - Braund, P. S.

AU - Hall, A. S.

AU - Samani, N. J.

AU - Thompson, J.

AU - März, W.

AU - Ouwehand, W.

AU - Sivapalaratnam, S.

AU - Soranzo, N.

AU - Trip, M.

AU - Lawlor, D. A.

AU - Casas, J. P.

AU - Ebrahim, S.

AU - Arsenault, B. J.

AU - Khaw, K. T.

AU - Ricketts, S. L.

AU - Sandhu, M. S.

AU - Wareham, N. J.

AU - Grallert, H.

AU - Illig, T.

AU - Humphries, S. E.

AU - Talmud, Talmud

AU - Rader, D. J.

AU - He, J.

AU - Reilly, M. P.

AU - Clarke, R.

AU - Hamsten, A.

AU - Hopewell, J. C.

AU - Watkins, H.

AU - Saleheen, D.

AU - Frossard, P.

AU - Deloukas, P.

AU - Danesh, J.

AU - Ye, S.

AU - Simpson, I. A.

AU - Kastelein, J. J.

AU - Marz, W.

AU - Hamsten, R.

AU - Simpson, J.A.

AU - Onat, A.

AU - Komurcu-Bayrak, E.

AU - Martinelli, N.

AU - Olivieri, O.

AU - Girelli, D.

AU - Kivimaki, M.

AU - Kumari, M.

AU - Aouizerat, B.E.

AU - Baum, L.

AU - Campos, H.

AU - Chaaba, R.

AU - Chen, B.S.

AU - Cho, E.Y.

AU - Evans, D.

AU - Hill, J.

AU - Hsu, L.A.

AU - Hubacek, J.A.

AU - Lai, C.Q.

AU - van der Lee, J. H.

AU - Klos, K.

AU - Liu, H.

AU - Masana, L.

AU - Melegh, B.

AU - Nabika, T.

AU - Ribalta, J.

AU - Ruiz-Narvaez, E.

AU - Thomas, G.N.

AU - Tomlinson, B.

AU - Szalai, C.

AU - Vaverkova, H.

AU - Yamada, Y.

AU - Yang, Y.

AU - Tipping, R.W.

AU - Ford, C.E.

AU - Pressel, S.L.

AU - Ballantyne, C.

AU - Brautbar, A.

AU - Knuiman, M.

AU - Winchup, P.H.

AU - Wannamethee, S.G.

AU - Morris, R.W.

AU - Kiechl, S.

AU - Willeit, J.

AU - Santer, P.

AU - Mayr, A.

AU - Wald, N.

AU - Dekker, J.M.

AU - Nijpels, G.

AU - White, I.R.

AU - Wood, A.M.

PY - 2010

Y1 - 2010

N2 - 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

AB - 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

U2 - https://doi.org/10.1016/S0140-6736(10)60545-4

DO - https://doi.org/10.1016/S0140-6736(10)60545-4

M3 - Article

C2 - 20452521

SN - 0140-6736

VL - 375

SP - 1634

EP - 1639

JO - Lancet

JF - Lancet

IS - 9726

ER -