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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Fulltext

    Forlagets udgivne version, 1,71 MB, PDF-dokument

  • Henry N Ginsberg
  • Chris J Packard
  • M John Chapman
  • Jan Borén
  • Carlos A Aguilar-Salinas
  • Maurizio Averna
  • Brian A. Ference
  • Daniel Gaudet
  • Robert A Hegele
  • Sander Kersten
  • Gary F. Lewis
  • Alice H. Lichtenstein
  • Philippe Moulin
  • Alan T Remaley
  • Bart Staels
  • Erik S. G. Stroes
  • Marja-Riitta Taskinen
  • Lale S Tokgözoğlu
  • Jane K. Stock
  • Alberico L Catapano

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.

OriginalsprogEngelsk
TidsskriftEuropean Heart Journal
Vol/bind42
Udgave nummer47
Sider (fra-til)4791-4806
Antal sider16
ISSN0195-668X
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
The European Atherosclerosis Society Consensus Panel met at a closed expert meeting in London in January 2020 to critically appraise and discuss evidence relating to the definition, aetiology and metabolism of TRL and their remnants, their role in ASCVD, and clinical management. Logistic support for travel was provided by the Society. There were no other sources of funding.

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/)

Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk


Ingen data tilgængelig

ID: 302811780