Triglyceride-rich lipoproteins and their remnants: Commentary on the 2021 EAS Consensus Statement

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The recent European Atherosclerosis Society Consensus Statement on triglyceride-rich lipoproteins (TRLs) and their remnants is the culmination of an 18-month wide-ranging review of the very complex relationship between elevated triglyceride levels and cardiovascular disease.¹ Professor Gary Lewis, Director of the Banting and Best Diabetes Centre at the University of Toronto, Canada, and co-author of the report discusses the evidence presented in this important publication and its implications for clinicians and patients.

Although abundant evidence shows that hypertriglyceridaemia is highly atherogenic, and a number of therapeutic measures have proven beneficial in preventing atherosclerosis in patients with elevated TGs,^1,2 decades of epidemiological studies have questioned whether triglyceride concentration is an independent predictor of cardiovascular disease. There has therefore been a great need for a really detailed evaluation of current knowledge of TRLs and remnant science and emerging therapeutic strategies.

The Consensus Group addressed key questions including those related to the major metabolic defects in hypertriglyceridaemia, accumulation of remnant particles, the impact of TRLs on other lipoprotein sub-classes and the role of TRLs in atherosclerosis.

The Group concluded that regulation of plasma levels of TGs, TRLs, and remnants is complex, and development of novel therapeutics that reduce ASCVD risk is challenging. However, improved understanding of these pathways will allow development of new therapeutics. A key question is whether to target lipolysis or production of particles or both. Many of the novel agents in development primarily target lipolysis and this appears to be quite effective. Bioassays that reflect lowering of TRLs and remnants incorporated into clinical trials will provide additional information about whether lowering these lipoproteins can reduce ASCVD.

There are three take-home messages from the Consensus Statement:

• A person identified as having elevated TG very commonly has features of the metabolic syndrome and is at moderate or high risk of cardiovascular disease, so it’s important not to view mild-to-moderate hypertriglyceridaemia in isolation
• TRL remnants are invariably elevated in those with hypertriglyceridaemia and elevated non-HDL cholesterol and are believed to be directly atherogenic
• There are a number of proven beneficial measures that should be considered and implemented in patients with moderate hypertriglyceridaemia and features of metabolic syndrome. These include diet and exercise, LDL or apoB lowering therapies (eg. statins, ezetimibe, PCSK9 inhibitors) and icosapent ethyl. Anti-hypertensive and anti-diabetes therapies, anti-platelet and anti-thrombotic therapies may also be indicated

An extended version of this article is available here » Read article

References

1. Ginsberg HN, Packard CJ, Chapman MJ et al. Triglyceride-rich lipoproteins and their remnants:metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society. European Heart Journal 2021 Dec 14;42(47):4791-4806. 
2. Lewis GF, Hegele RA. Effective, disease-modifying, clinical approaches to patients with mild-to-moderate hypertriglyceridaemia. Lancet Diabetes Endocrinol. 2021 Dec 16:S2213-8587(21)00284-9