HDL Triglycerides: A New Marker of Metabolic and Cardiovascular Risk

Abstract

While cholesterol content in high-density lipoproteins (HDLs) is a well-established inverse marker of cardiovascular risk, the importance of HDL–triglyceride (HDL-TG) concentration is not well known. We aim to examine plasma HDL-TG concentrations, assessed by 1H-NMR, in patients with metabolic diseases and their association with classical biomarkers. In this cross-sectional study, we included 502 patients with type 2 diabetes or metabolic syndrome attending the lipid unit of our University Hospital. The presence of arteriosclerotic plaques was assessed by ultrasonography. A complete lipoprotein profile was performed by 1H-NMR (Liposcale test). HDL-TG was strongly positively correlated with total triglycerides, glycerol, and fatty liver index, while a strong negative correlation was observed with HDL-cholesterol (HDL-C) and HDL-particle number (HDL-P). HDL-TG was associated with all triglyceride-rich lipoprotein parameters and had an opposite association with HDL-C and HDL-P. It was also significantly correlated with circulating cholesterol ester transfer protein (CETP). HDL-TG concentrations were higher as metabolic syndrome components increased. HDL-TG was also higher with worsening glucose metabolism. Patients with carotid plaques also showed higher HDL-TG. In contrast to HDL-C, HDL-TG is directly associated with metabolism and arteriosclerotic vascular alterations. HDL-TG should be considered a biomarker of metabolic and cardiovascular risk and could be a marker of HDL dysfunction.

Coagulatory Defects in Type-1 and Type-2 Diabetes

“…This results in impaired HDL structure, as the hydrophobic core of the triglycerides partially extrude to the HDL surface [138], and therefore impaired HDL function [139], and (eventually) endothelial dysfunction. Contrary to HDL-cholesterol levels, HDL-triglycerides have been shown to be an effective marker of increased cardiovascular risk in the general population [140] and in individuals with T2DM or with metabolic syndrome [137].…”

“…Hypertriglyceridemia is often associated with T1DM and T2DM [134][135][136]. Cholesterol ester transfer protein (CETP) exchanges cholesterol and triglycerides between very low-density lipoprotein and HDL [137]. When the plasma level of triglycerides is too high, the equilibrium is displaced, and HDL are impoverished in cholesterol and enriched in triglycerides [137].…”

“…Cholesterol ester transfer protein (CETP) exchanges cholesterol and triglycerides between very low-density lipoprotein and HDL [137]. When the plasma level of triglycerides is too high, the equilibrium is displaced, and HDL are impoverished in cholesterol and enriched in triglycerides [137]. This results in impaired HDL structure, as the hydrophobic core of the triglycerides partially extrude to the HDL surface [138], and therefore impaired HDL function [139], and (eventually) endothelial dysfunction.…”

“…In addition, drugs designed to increase HDL-cholesterol levels such as niacin, fenofibrate and CETP inhibitors have been designed. It is important to highlight though that these drugs fail to further decrease cardiovascular risk when administered to individuals already taking statins [137]. Nevertheless, fenofibrates also have some effect on the coagulation system, including decreasing levels of fibrinogen, tissue factor, factor VII and PAI-1 [4].…”

High Density Lipoproteins: Metabolism, Function, and Therapeutic Potential

“…Alterations in the lipidome, such as increase in triglycerides or decrease in phospholipids (67,68), or a concomitant increase in surface rigidity due to an altered sphingomyelin to cholesterol ratio, reduce the RCT ability of HDLs, and its ability to associate to beneficial enzymes and proteins (69). Recent studies suggest that HDL-triglycerides measurement may be a useful biomarker to determine HDL quality and HDL function over HDL-C (70). While it has been widely accepted that oxidation and glycation of HDLs are a major driver of HDL dysfunction in-vivo (71, 72), a few studies challenge this view, finding either no dysfunction (73) or improved function (24,74) following either endogenous or artificial oxidation of HDL.…”