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Non-alcoholic fatty liver disease-related risk of cardiovascular disease and other cardiac complications

Non-alcoholic fatty liver disease-related risk of cardiovascular disease and other cardiac complications
Non-alcoholic fatty liver disease-related risk of cardiovascular disease and other cardiac complications

Background/Aim: Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global adult population. The aim of this narrative review is to describe the associations between NAFLD and cardiovascular disease (CVD), arrhythmias, cardiac conduction defects, myocardial remodelling and heart failure. We also discuss the potential mechanisms that mediate or attenuate the strength of these associations, and briefly summarize the effect of treatments that both ameliorate NAFLD and decrease risk of CVD. Methods: Searches of PubMed were performed by the two authors using the terms listed in Appendix. We limited the timeframe to the last decade due to the vast amount of research in the field (up to April 2021) for meta-analyses, reviews and original papers. Only articles published in English were considered. Results: NAFLD is associated with an increased risk of fatal/non-fatal CVD events and other cardiac and arrhythmic complications (left ventricular hypertrophy, aortic-valve sclerosis and certain arrhythmias), independently of common CVD risk factors. There are probably several underlying mechanisms, including hepatic/systemic insulin resistance, atherogenic dyslipidaemia, hypertension and pro-atherogenic, pro-coagulant and pro-inflammatory mediators released from the steatotic/inflamed liver that may be involved. Some genetic polymorphisms, such as PNPLA3 (rs738409 C>G) and TM6SF2 (rs58542926 C>T), may worsen the liver disease, but also attenuate the strength of the association between NAFLD and CVD, possibly via their effects on lipoprotein metabolism. Of the currently tested drugs for treating NAFLD that also benefit the vasculature, pioglitazone and GLP-1 receptor agonists are the most promising. Conclusions: The complex interplay between the liver and cardiometabolic risk factors contributes to CVD, arrhythmias and cardiac disease in NAFLD. There is an urgent need for a multidisciplinary approach to manage both liver disease and cardiometabolic risk, and to test the cardiovascular and cardiac effects of new drugs for NAFLD.

CVD, NAFLD, arrhythmias, cardiovascular disease, conduction defects, heart failure, nonalcoholic fatty liver disease
1462-8902
28-43
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f

Byrne, Christopher and Targher, Giovanni (2022) Non-alcoholic fatty liver disease-related risk of cardiovascular disease and other cardiac complications. Diabetes, Obesity and Metabolism, 24 (S2), 28-43. (doi:10.1111/dom.14484).

Record type: Article

Abstract

Background/Aim: Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global adult population. The aim of this narrative review is to describe the associations between NAFLD and cardiovascular disease (CVD), arrhythmias, cardiac conduction defects, myocardial remodelling and heart failure. We also discuss the potential mechanisms that mediate or attenuate the strength of these associations, and briefly summarize the effect of treatments that both ameliorate NAFLD and decrease risk of CVD. Methods: Searches of PubMed were performed by the two authors using the terms listed in Appendix. We limited the timeframe to the last decade due to the vast amount of research in the field (up to April 2021) for meta-analyses, reviews and original papers. Only articles published in English were considered. Results: NAFLD is associated with an increased risk of fatal/non-fatal CVD events and other cardiac and arrhythmic complications (left ventricular hypertrophy, aortic-valve sclerosis and certain arrhythmias), independently of common CVD risk factors. There are probably several underlying mechanisms, including hepatic/systemic insulin resistance, atherogenic dyslipidaemia, hypertension and pro-atherogenic, pro-coagulant and pro-inflammatory mediators released from the steatotic/inflamed liver that may be involved. Some genetic polymorphisms, such as PNPLA3 (rs738409 C>G) and TM6SF2 (rs58542926 C>T), may worsen the liver disease, but also attenuate the strength of the association between NAFLD and CVD, possibly via their effects on lipoprotein metabolism. Of the currently tested drugs for treating NAFLD that also benefit the vasculature, pioglitazone and GLP-1 receptor agonists are the most promising. Conclusions: The complex interplay between the liver and cardiometabolic risk factors contributes to CVD, arrhythmias and cardiac disease in NAFLD. There is an urgent need for a multidisciplinary approach to manage both liver disease and cardiometabolic risk, and to test the cardiovascular and cardiac effects of new drugs for NAFLD.

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Diabetes Obesity Metabolism Invited Review_Byrne Targher_R1 final - Accepted Manuscript
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More information

Accepted/In Press date: 27 June 2021
e-pub ahead of print date: 29 July 2021
Published date: February 2022
Additional Information: Funding Information: CDB is supported in part by the Southampton NIHR Biomedical Research Centre (IS‐BRC‐20004), UK. GT is supported by grants from the University of Verona, Italy. Publisher Copyright: © 2021 John Wiley & Sons Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords: CVD, NAFLD, arrhythmias, cardiovascular disease, conduction defects, heart failure, nonalcoholic fatty liver disease

Identifiers

Local EPrints ID: 450062
URI: http://eprints.soton.ac.uk/id/eprint/450062
ISSN: 1462-8902
PURE UUID: a7dfded1-0574-45e3-b444-1fad0bdfb0c6
ORCID for Christopher Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 07 Jul 2021 16:31
Last modified: 24 Jul 2022 01:36

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Author: Giovanni Targher

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