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Mechanisms of Disease: lessons from ethnicity in the role of triglyceride metabolism in ischemic heart disease

Nature Clinical Practice Endocrinology & Metabolism volume 3, pages 530–538 (2007)Cite this article

Abstract

Mean risk factor levels in various ethnic groups illustrate the potential importance of triglyceride metabolism in the risk for ischemic heart disease (IHD). Serum triglyceride concentrations are a surrogate for a range of potentially atherogenic disturbances in lipoprotein species, including increased concentrations of remnants of VLDL and chylomicron metabolism, increased small, dense LDL concentrations and reduced HDL concentrations. Differences between at-risk groups in lipoprotein profiles reflect alterations in the metabolism of triglycerides that might be greater than differences observed when only circulating triglyceride concentrations are measured. This atherogenic lipoprotein profile is typically found in association with increased visceral fat, insulin resistance and type 2 diabetes and might be a characteristic of Asian Indian ethnicity. By contrast, despite being relatively insulin resistant, Afro-Caribbean men in the UK have a low risk of IHD and lack the adverse lipoprotein profile. This could result from secretion of relatively large proportions of their VLDL as small, triglyceride-poor particles, levels of which are not augmented in response to loss of insulin action. These considerations re-endorse the potential importance of triglyceride metabolism in IHD and present opportunities for identifying useful areas in which drug targets for reducing IHD risk can be sought.

Key Points

  • Mean triglyceride concentrations are the strongest covariate with variation in ischemic heart disease according to ethnicity, sex and diabetes

  • The importance of triglycerides is likely to have been underestimated in risk-factor studies

  • Triglyceride levels provide an index of the atherogenic lipoprotein profile

  • Differences in features of the atherogenic lipoprotein profile according to ethnicity, sex and diabetes might be greater than differences in triglycerides

  • The paradoxical association between insulin resistance, high risk of diabetes, low expression of the atherogenic lipoprotein profile and low risk of ischemic heart disease in Afro-Caribbeans might be explained by their increased secretion of small, triglyceride-poor VLDL

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Figure 1: The relationship between risk of heart disease and triglyceride levels
Figure 2: Inter-relationships between visceral fat, insulin action and the atherogenic lipoprotein profile
Figure 3: Ethnic differences in the relationship between triglycerides, abdominal fat and insulin resistance

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Acknowledgements

IF Godsland is supported by the Heart Disease and Diabetes Research Trust. We thank N Forouhi, T Tillin and P McKeigue for their critical readings of the manuscript and supporting data analysis.

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Authors and Affiliations

  1. in the Division of Medicine, IF Godsland is Wynn Reader in Human Metabolism, Endocrinology and Metabolic Medicine, and DG Johnston is Professor of Endocrinology and Metabolic Medicine, Endocrinology and Metabolic Medicine, Imperial College London, London, UK.,

    Ian F Godsland & Desmond G Johnston

  2. N Chaturvedi is Professor of Cardiovascular Epidemiology, in the National Heart and Lung Institute, Imperial College London.,

    Nishi Chaturvedi

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  1. Ian F Godsland
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Correspondence to Ian F Godsland.

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Godsland, I., Johnston, D. & Chaturvedi, N. Mechanisms of Disease: lessons from ethnicity in the role of triglyceride metabolism in ischemic heart disease. Nat Rev Endocrinol 3, 530–538 (2007). https://doi.org/10.1038/ncpendmet0530

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