Wednesday News from EAS Congress:
Triglycerides are very much on the ‘up.’ Professor Peter Libby (Brigham & Women’s Hospital, Harvard Medical School, Boston, USA) discussed triglycerides at the Joint EAS/International Atherosclerosis Society session. Furthermore, triglyceride metabolism was also the focus of this year’s key note lecture by Professor Chris Packard (University of Glasgow, UK).
Triglyceride metabolism is central to a range of pathologies, including atherosclerotic cardiovascular disease, nonalcoholic fatty liver disease, type 2 diabetes mellitus and acute pancreatitis. To understand this interconnection it is necessary to build a mechanistic and regulatory framework.
The role of triglyceride-rich lipoproteins (TRL) and their remnants in atherosclerosis has been debated for decades. Crucial to this question is understanding the aetiology of these TRL; whether they are intestinal– or hepatic-derived apolipoprotein (apo) B-containing lipoproteins. A key differentiating feature is the inclusion of apoB100 (for those of hepatic origin) or apoB48. As discussed, it is the cholesterol-containing component of TRL and their remnants that is linked with atherosclerosis, and is relevant to residual cardiovascular risk (1).
In individuals with elevated plasma triglycerides, there is greater pressure on the lipolytic system; however, concomitant reduced lipolytic efficiency results in further accumulation of cholesteryl ester within remnant particles, mostly in the very low-density lipoprotein (VLDL) range, and persistence of these lipoproteins in the circulation. As discussed by Professor Packard, the characterisation of remnants reinforces that they are a potent atherogenic lipoprotein. However, measuring remnant levels accurately and reliably is one of the challenges for researchers in this field.
Focusing on intestinal lipoprotein metabolism, studies have shown that in individuals with type 2 diabetes mellitus, there is exaggerated apoB48 production, resulting in overproduction of chylomicrons and VLDL, which has consequences for remnant formation, especially in the postprandial state. Across the day, between 25-30% of long-lived particles in VLDL density are of intestinal origin. Thus, the intestine is an important contributor to the remnant population in type 2 diabetes.
Finally, Professor Packard discussed the clinical consequences of TRL and remnant metabolism for NAFLD and coronary artery disease. Numerous reviews imply that these two pathological conditions are linked, possibly via inflammation and thrombosis or via dyslipidaemia. He commented that the emerging evidence suggests that it is the triglyceride transport phenomena that link these conditions.
Providing a mechanistic framework to understand TRL metabolism and the contributing roles of the intestine offers approaches for regulating triglyceride metabolism. Understanding this has led to the development of novel targets with therapeutic potential, including apoCIII and ANGPTL3, which are the focus of new clinical treatments.
View these lectures and other lectures from the Congress on demand
- Vallejo-Vaz AJ, Fayyad R, Boekholdt SM, et al. Triglyceride-rich lipoprotein cholesterol and risk of cardiovascular events among patients receiving statin therapy in the TNT Trial. Circulation 2018;138:770-81.
For further reading:
- Packard CJ, Borén J, Taskinen MR. Causes and consequences of hypertriglyceridemia. Front Endocrinol (Lausanne) 2020;11:252.
- Chait A, Ginsberg HN, Vaisar T, et al. Remnants of the triglyceride-rich lipoproteins, diabetes, and cardiovascular disease. Diabetes 2020;69:508-16.
- Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology. Circ Res 2016;118:547-63.
- Chapman MJ, Ginsberg HN, Amarenco P, et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32:1345‐1361