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  • Review Article
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Demystifying the management of hypertriglyceridaemia

Nature Reviews Cardiology volume 10, pages 648–661 (2013)Cite this article

Subjects

Key Points

  • Hypertriglyceridaemia is a common indicator of cardiometabolic risk factors and atherosclerotic cardiovascular disease (CVD)

  • Hypertriglyceridaemia can be caused by genetic and nongenetic factors, such as obesity, insulin resistance, and type 2 diabetes mellitus

  • Moderately elevated plasma triglyceride concentrations (1.7–5.0 mmol/l) reflect the accumulation of triglyceride-rich lipoprotein (TRL) remnants and small dense LDL particles that are highly atherogenic

  • Treatment of hypertriglyceridaemia involves correction of secondary factors and unhealthy lifestyle habits; pharmacotherapy is indicated for patients with established CVD or those at moderate-to-high risk of CVD

  • Statin therapy is the cornerstone of pharmacological treatment for hypertriglyceridaemia, followed by fibrates and n-3 fatty acids to achieve recommended target levels of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B-100 in plasma

  • Several agents that regulate TRL metabolism are in development, but their clinical efficacy, safety, cost-effectiveness, and indications are yet to be established

Abstract

Hypertriglyceridaemia (typical triglyceride level 1.7–5.0 mmol/l) is caused by interactions between many genetic and nongenetic factors, and is a common risk factor for atherosclerotic cardiovascular disease (CVD). Patients with hypertriglyceridaemia usually present with obesity, insulin resistance, hepatic steatosis, ectopic fat deposition, and diabetes mellitus. Hypertriglyceridaemia reflects the accumulation in plasma of proatherogenic lipoproteins, triglyceride-rich lipoprotein (TRL) remnants, and small, dense LDL particles. Mendelian randomization studies and research on inherited dyslipidaemias, such as type III dysbetalipoproteinaemia, testify that TRLs are causally related to atherosclerotic CVD. Extreme hypertriglyceridaemia (a triglyceride level >20 mmol/l) is rare, often monogenic in aetiology, and frequently causes pancreatitis. Treatment of hypertriglyceridaemia relies on correcting secondary factors and unhealthy lifestyle habits, particularly poor diet and lack of exercise. Pharmacotherapy is indicated for patients with established CVD or individuals at moderate-to-high risk of CVD, primarily those with metabolic syndrome or diabetes. Statins are the cornerstone of treatment, followed by fibrates and n-3 fatty acids, to achieve recommended therapeutic levels of plasma LDL cholesterol, non-HDL cholesterol, and apolipoprotein (apo) B-100. The case for using niacin has been weakened by the results of clinical trials, but needs further investigation. Extreme hypertriglyceridaemia requires strict dietary measures, and patients with a diagnosis of genetic lipoprotein lipase deficiency might benefit from LPL gene replacement therapy. Several therapies for regulating TRL metabolism, including inhibitors of diacylglycerol O-acyltransferase and microsomal triglyceride transfer protein, and apoC-III antisense oligonucleotides, merit further investigation in patients with hypertriglyceridaemia.

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Figure 1: Pathogenesis of atherogenic dyslipidaemia in the setting of hypertriglyceridaemia, insulin resistance, and hepatic steatosis; central obesity and type 2 diabetes mellitus are common clinical phenotypes.
Figure 2: Hypertriglyceridaemia, triglyceride-rich lipoproteins, and atherogenesis.
Figure 3: Non-HDL-cholesterol concentration in plasma is the sum of cholesterol in triglyceride-rich lipoproteins (chylomicrons, chylomicron remnants, VLDL and IDL) and LDL, which can be estimated by subtracting the HDL-cholesterol concentration from the total plasma cholesterol concentration.
Figure 4: Algorithm for managing dyslipidaemia in patients at high risk of cardiovascular disease.

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Acknowledgements

E. M. M. Ooi is an NHMRC Postdoctoral Fellow. D. C. Chan is a National Health and Medical Research Council (NHMRC) Career Development Fellow.

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  1. Lipid Disorders Clinic and Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, PO Box X2213, Perth, 6847, WA, Australia

    Gerald F. Watts, Esther M. M. Ooi & Dick C. Chan

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All the authors researched data for the article, contributed substantially to the discussion of content, wrote the manuscript, and reviewed/edited the manuscript before submission.

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G. F. Watts has received honoraria for advisory board memberships and lectures from Abbott, Amgen, Genfit, Merck & Co., and Sanofi. The other authors declare no competing interests.

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Watts, G., Ooi, E. & Chan, D. Demystifying the management of hypertriglyceridaemia. Nat Rev Cardiol 10, 648–661 (2013). https://doi.org/10.1038/nrcardio.2013.140

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