Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

By M. Chapman, H. Ginsberg, P. Amarenco, F. Andreotti, Jan Boren, A. Catapano, O. Descamps, E. Fisher, P. Kovanen, J. Kuivenhoven and 9 more. European Heart Journal, 2011

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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 high-density 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.

Subfields: Cancer Research, Endocrinology, Diabetes and Metabolism, Surgery

View Paper: https://www.semanticscholar.org/paper/45f95c2cc9fe1ac7defbdab8c28b129aadd1667f

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Citations in the corpus

European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (Version 2012) (2012, neutral): “5 High-density lipoprotein cholesterol Low concentrations of HDL cholesterol are independently associated with higher CVD risk, therefore HDL cholesterol is also included in new SCORE charts.(478) The combination of moderately elevated triglycerides and low concentrations of HDL cholesterol is very ”
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 (2021, background): “2,94,95,97,98 This involves major modification of the HDL proteome and lipidome, 99,100 resulting in attenuated vasculoprotective functions including reverse cholesterol transport, inhibition of oxidation, and anti-inflammatory activities.”
2016 European Guidelines on cardiovascular disease prevention in clinical practice (2017, neutral): “Low HDL-C is independently associated with higher CVD risk [359].”
Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel (2020, background): “and Lp(a) are directly causal in ASCVD, independent of LDL-C levels.(6,7,9,11) Indeed, the hazard ratios for myocardial infarction for a”
2016 European Guidelines on cardiovascular disease prevention in clinical practice (2016, background): “5 High-density lipoprotein cholesterol Low HDL-C is independently associated with higher CVD risk.(359)”
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. (2016, background): “10 mmol/L is defined as severe HTG.(260) Age/gender, race/ethnicity and lifestyle are modulating factors at the population level for serum TGs.”
Remnant cholesterol as a causal risk factor for ischemic heart disease. (2013, background): “these 2 lipoproteins together with chylomicron remnants in the nonfasting state (1,2).”
2016 European Guidelines on cardiovascular disease prevention in clinical practice. (2016, background): “5 High-density lipoprotein cholesterol Low HDL-C is independently associated with higher CVD risk.(359)”
Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart Disease (2013, neutral): “indirectly following liberation of lipolytic products (such as FFA and lysolecithin) which may activate pro-inflammatory signalling pathways in endothelial cells [51].”