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

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.

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Main Authors: Ginsberg, Henry N., Packard, Chris J., Chapman, John, Borén, Jan, Aguilar-Salinas, Carlos A., Averna, Maurizio, Ference, Brian A., Gaudet, Daniel, Hegele, Robert A., Kersten, Sander, Lewis, Gary F., Lichtenstein, Alice H., Moulin, Philippe, Nordestgaard, Børge G., Remaley, Alan T., Staels, Bart, Stroes, Erik S.G., Taskinen, Marja Riitta, Tokgözoğlu, Lale S., Tybjaerg-Hansen, Anne, Stock, Jane K., Catapano, Alberico L.
Format: Article/Letter to editor biblioteca
Language:English
Subjects:Cardiovascular disease, Lipoprotein remnants, Residual risk, Triglyceride-rich lipoproteins, Triglycerides,
Online Access:https://research.wur.nl/en/publications/triglyceride-rich-lipoproteins-and-their-remnants-metabolic-insig
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spelling dig-wur-nl-wurpubs-5936922024-10-02 Ginsberg, Henry N. Packard, Chris J. Chapman, John Borén, Jan Aguilar-Salinas, Carlos A. Averna, Maurizio Ference, Brian A. Gaudet, Daniel Hegele, Robert A. Kersten, Sander Lewis, Gary F. Lichtenstein, Alice H. Moulin, Philippe Nordestgaard, Børge G. Remaley, Alan T. Staels, Bart Stroes, Erik S.G. Taskinen, Marja Riitta Tokgözoğlu, Lale S. Tybjaerg-Hansen, Anne Stock, Jane K. Catapano, Alberico L. Article/Letter to editor European Heart Journal 42 (2021) 47 ISSN: 0195-668X 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 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. en application/pdf https://research.wur.nl/en/publications/triglyceride-rich-lipoproteins-and-their-remnants-metabolic-insig 10.1093/eurheartj/ehab551 https://edepot.wur.nl/563778 Cardiovascular disease Lipoprotein remnants Residual risk Triglyceride-rich lipoproteins Triglycerides https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/ Wageningen University & Research
institution WUR NL
collection DSpace
country Países bajos
countrycode NL
component Bibliográfico
access En linea
databasecode dig-wur-nl
tag biblioteca
region Europa del Oeste
libraryname WUR Library Netherlands
language English
topic Cardiovascular disease
Lipoprotein remnants
Residual risk
Triglyceride-rich lipoproteins
Triglycerides
Cardiovascular disease
Lipoprotein remnants
Residual risk
Triglyceride-rich lipoproteins
Triglycerides
spellingShingle Cardiovascular disease
Lipoprotein remnants
Residual risk
Triglyceride-rich lipoproteins
Triglycerides
Cardiovascular disease
Lipoprotein remnants
Residual risk
Triglyceride-rich lipoproteins
Triglycerides
Ginsberg, Henry N.
Packard, Chris J.
Chapman, John
Borén, Jan
Aguilar-Salinas, Carlos A.
Averna, Maurizio
Ference, Brian A.
Gaudet, Daniel
Hegele, Robert A.
Kersten, Sander
Lewis, Gary F.
Lichtenstein, Alice H.
Moulin, Philippe
Nordestgaard, Børge G.
Remaley, Alan T.
Staels, Bart
Stroes, Erik S.G.
Taskinen, Marja Riitta
Tokgözoğlu, Lale S.
Tybjaerg-Hansen, Anne
Stock, Jane K.
Catapano, Alberico L.
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
description 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.
format Article/Letter to editor
topic_facet Cardiovascular disease
Lipoprotein remnants
Residual risk
Triglyceride-rich lipoproteins
Triglycerides
author Ginsberg, Henry N.
Packard, Chris J.
Chapman, John
Borén, Jan
Aguilar-Salinas, Carlos A.
Averna, Maurizio
Ference, Brian A.
Gaudet, Daniel
Hegele, Robert A.
Kersten, Sander
Lewis, Gary F.
Lichtenstein, Alice H.
Moulin, Philippe
Nordestgaard, Børge G.
Remaley, Alan T.
Staels, Bart
Stroes, Erik S.G.
Taskinen, Marja Riitta
Tokgözoğlu, Lale S.
Tybjaerg-Hansen, Anne
Stock, Jane K.
Catapano, Alberico L.
author_facet Ginsberg, Henry N.
Packard, Chris J.
Chapman, John
Borén, Jan
Aguilar-Salinas, Carlos A.
Averna, Maurizio
Ference, Brian A.
Gaudet, Daniel
Hegele, Robert A.
Kersten, Sander
Lewis, Gary F.
Lichtenstein, Alice H.
Moulin, Philippe
Nordestgaard, Børge G.
Remaley, Alan T.
Staels, Bart
Stroes, Erik S.G.
Taskinen, Marja Riitta
Tokgözoğlu, Lale S.
Tybjaerg-Hansen, Anne
Stock, Jane K.
Catapano, Alberico L.
author_sort Ginsberg, Henry N.
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
url https://research.wur.nl/en/publications/triglyceride-rich-lipoproteins-and-their-remnants-metabolic-insig
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