TY - JOUR

T1 - Triglyceride-rich lipoproteins and their remnants

T2 - Metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies - a consensus statement from the European Atherosclerosis Society

AU - Ginsberg, Henry N

AU - Packard, Chris J

AU - Chapman, M John

AU - Borén, Jan

AU - Aguilar-Salinas, Carlos A

AU - Averna, Maurizio

AU - Ference, Brian A.

AU - Gaudet, Daniel

AU - Hegele, Robert A

AU - Kersten, Sander

AU - Lewis, Gary F.

AU - Lichtenstein, Alice H.

AU - Moulin, Philippe

AU - Nordestgaard, Børge G.

AU - Remaley, Alan T

AU - Staels, Bart

AU - Stroes, Erik S. G.

AU - Taskinen, Marja-Riitta

AU - Tokgözoğlu, Lale S

AU - Tybjaerg-Hansen, Anne

AU - Stock, Jane K.

AU - Catapano, Alberico L

N1 - Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/)

PY - 2021

Y1 - 2021

N2 - Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis. These data also indicate that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding of the structure, function, and metabolism of TRL, and their pathophysiological role in atherosclerotic cardiovascular disease (ASCVD). Key points are (i) a working definition of normo- and hypertriglyceridaemic states and their relation to risk of ASCVD, (ii) a conceptual framework for the generation of remnants due to dysregulation of TRL production, lipolysis, and remodelling, as well as clearance of remnant lipoproteins from the circulation, (iii) the pleiotropic proatherogenic actions of TRL and remnants at the arterial wall, (iv) challenges in defining, quantitating, and assessing the atherogenic properties of remnant particles, and (v) exploration of the relative atherogenicity of TRL and remnants compared to LDL. Assessment of these issues provides a foundation for evaluating approaches to effectively reduce levels of TRL and remnants by targeting either production, lipolysis, or hepatic clearance, or a combination of these mechanisms. This consensus statement updates current understanding in an integrated manner, thereby providing a platform for new therapeutic paradigms targeting TRL and their remnants, with the aim of reducing the risk of ASCVD.

AB - Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis. These data also indicate that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding of the structure, function, and metabolism of TRL, and their pathophysiological role in atherosclerotic cardiovascular disease (ASCVD). Key points are (i) a working definition of normo- and hypertriglyceridaemic states and their relation to risk of ASCVD, (ii) a conceptual framework for the generation of remnants due to dysregulation of TRL production, lipolysis, and remodelling, as well as clearance of remnant lipoproteins from the circulation, (iii) the pleiotropic proatherogenic actions of TRL and remnants at the arterial wall, (iv) challenges in defining, quantitating, and assessing the atherogenic properties of remnant particles, and (v) exploration of the relative atherogenicity of TRL and remnants compared to LDL. Assessment of these issues provides a foundation for evaluating approaches to effectively reduce levels of TRL and remnants by targeting either production, lipolysis, or hepatic clearance, or a combination of these mechanisms. This consensus statement updates current understanding in an integrated manner, thereby providing a platform for new therapeutic paradigms targeting TRL and their remnants, with the aim of reducing the risk of ASCVD.

KW - Cardiovascular disease

KW - Lipoprotein remnants

KW - Residual risk

KW - Triglyceride-rich lipoproteins

KW - Triglycerides

U2 - 10.1093/eurheartj/ehab551

DO - 10.1093/eurheartj/ehab551

M3 - Journal article

C2 - 34472586

AN - SCOPUS:85117893974

VL - 42

SP - 4791

EP - 4806

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 47

ER -