32 Triglyceride-Rich Lipoproteins and High-Density Lipoprotein Cholesterol in Patients at High Risk of Cardiovascular Disease: Evidence and Guidance for Management

Abstract

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of highdensity lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (,1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.--

Effects of dietary fish oil replacements with three vegetable oils on growth, fatty acid composition, antioxidant capacity, serum parameters and expression of lipid metabolism related genes in juvenile Onychostoma macrolepis

“…In this study, the serum HDL-c level of the fish in the SO group was significantly decreased compared with that of the fish in the FO group. Previous studies reported that elevated TG levels were always accompanied by decreased HDL-c levels, suggesting an inverse correlation between these two serum indicators (Chapman et al, 2011;Joseph et al, 2014). In this study, the blood fat indicator in the fish of the AO group was similar to that with the FO group, which was in agreement with what were previously reported, showing that n-3 LC-PUFA from AO probably reduce serum TG level (Bernstein et al, 2012).…”

The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans

“…Fructose induced not only increased expression of APOC3 (111,113), but also increased hepatic de novo lipogenesis of fatty acids that is an important initiator of NAFLD and overproduction of triglyceride-rich VLDL 1 particles (43,61,(118)(119)(120)(121)(122). The relative importance of increased liver fat vs. increased secretion of apoC-III for fructose-induced hypertriglyceridemia, remains to clarified.…”

Causes and Consequences of Hypertriglyceridemia

“…The case for cholesterolcarrying low-density lipoprotein (LDL) as a causal factor for ASCVD is well made (4, 5) but until recently there has been significant doubt as to the role of raised plasma triglyceride, carried in chylomicrons and very-low density lipoproteins (VLDL) (collectively termed triglyceriderich lipoproteins, TRL), as a risk factor for the development of atherosclerosis. Epidemiological studies in the general population consistently demonstrate a strong, positive association of plasma triglyceride levels with risk of ASCVD (2,3,6,7) but this has been considered confounded, mainly by the link between higher levels of TRL and decreased concentrations of high-density lipoproteins (HDL), a lipoprotein class with putative cardio-protective properties (3,8). A resurgence of interest in triglyceride as a causative agent for ASCVD and as a possible target for intervention followed reports that common allelic variations in genes regulating specifically triglyceride metabolism are associated with differences in cardiovascular disease outcomes (9)(10)(11), thus addressing the confounding issue, and that lowering plasma triglyceride is associated with reduced risk of a major cardiovascular event (12) (but may not be the whole explanation for the benefit seen in that trial).…”

“…The fate of the contained lipid is directed by proteins on the particle surface that interact with key lipolytic enzymes and cell membrane receptors. It is recognized that the levels of plasma triglyceride and cholesterol in most populations are far in excess of the concentrations needed to support physiological processes and this leads to pathological consequences such as atherosclerotic cardiovascular disease (ASCVD) and pancreatitis (1)(2)(3). The case for cholesterolcarrying low-density lipoprotein (LDL) as a causal factor for ASCVD is well made (4, 5) but until recently there has been significant doubt as to the role of raised plasma triglyceride, carried in chylomicrons and very-low density lipoproteins (VLDL) (collectively termed triglyceriderich lipoproteins, TRL), as a risk factor for the development of atherosclerosis.…”

“…Reduced levels of high-density lipoprotein (HDL) which are a further consequence of raised triglyceride levels may contribute to the enhanced risk (3) but it is unclear whether a change in HDL attendant on triglyceride lowering will result in decreased CVD risk. Mendelian randomization studies do not support a causative link and outcome trials targeting HDL have failed to show a risk reduction (3,8,19).…”