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Review
. 2025 Jan 7;151(1):98-119.
doi: 10.1161/CIRCULATIONAHA.124.070535. Epub 2024 Dec 26.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach

Nicholas W S Chew #  1   2 , Anurag Mehta #  3 , Rachel Sze Jen Goh  2 , Audrey Zhang  1 , Yiming Chen  2 , Bryan Chong  2 , Han Shi Jocelyn Chew  4 , Asim Shabbir  5 , Adrian Brown  6 , Georgios K Dimitriadis  7 , Daniel Q Huang  8   2   9 , Roger Foo  1   2 , Carel W le Roux  10 , Gemma A Figtree  11 , Marat Fudim  12 , Ambarish Pandey  13 , Mamas A Mamas  14 , Derek J Hausenloy  2   15   16 , A Mark Richards  17   18 , Stephen J Nicholls  19 , Mark Y Chan  1   2 , Mark D Muthiah  8   2   9 , Arun Sanyal  20 , Laurence S Sperling  21
Affiliations
Review

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach

Nicholas W S Chew et al. Circulation. .

Abstract

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health. Metabolic dysfunction and associated insulin resistance, together with the predilection for ectopic fat deposition in the liver and surrounding tissues, are associated with elevated risk of endothelial dysfunction, systemic inflammatory response, and ectopic fat deposition in the epicardium. This complex pathophysiology can accelerate atherogenic dyslipidemia, atherogenesis, diastolic dysfunction, valvular calcification, and cardiac arrhythmias. Despite the mounting evidence of mechanistic pathways underpinning MASLD and CVD, current recommendations have not clearly focused upon MASLD as a risk factor or target for intervention in CVD. We have brought together a diverse range of international experts committed to promoting cardiovascular-liver-metabolic health and related outcomes across the globe. The overarching goal of this document is to offer a construct for clinicians in the cardiovascular field with regards to (1) diagnosis and screening of MASLD through the use of noninvasive serum and imaging tests; (2) screening for CVD in all individuals with MASLD regardless of established atherosclerotic risk factors; and (3) the approach to management of MASLD with respect to prevention of CVD through lifestyle, as well as pharmacologic and surgical strategies. To achieve this, the modified Delphi method was applied and a series of evidence-based quality standard recommendations have been identified.

Keywords: atherosclerosis; cardiovascular diseases; fatty liver; isk factors; liver diseases; metabolic syndrome.

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Conflict of interest statement

N.W.S.C reports research support from the National University Health System’s Seed Fund (grant No. NUHSRO/2022/RO5+6/Seed-Mar/03) and Clinician Scientist Program (grant No. NCSP2.0/2024/NUHS/NCWS), National Medical Research Council Research Training Fellowship (grant No. MH 095:003/008-303), and National University of Singapore Yong Loo Lin School of Medicine’s Academic Fellowship Scheme. A.M. reports research grants from Novartis and Amgen. G.K.D reports research grants from National Institute for Health and Care Research, Novo Nordisk UK Research Foundation, and DDM, as well as payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novo Nordisk, Rhythm Pharmaceuticals, Johnson & Johnson/Ethicon, and Medtronic. C.W.l.R reports grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board; serves on advisory boards of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, and Boehringer Ingelheim; is a member of the Irish Society for Nutrition and Metabolism, outside the area of work commented on here; was Chief Medical Officer and Director of the Medical Device Division of Keyron in 2011 (both unremunerated positions); and was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. The product has only been tested in rodents and none of Keyron’s products are currently licensed. They do not have any contracts with other companies to put their products into clinical practice. No patients have been included in any of Keyron’s studies and they are not listed on the stock market. C.W.l.R was also gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021, and continues to provide scientific advice to Keyron for no remuneration. G.A.F. reports grants from National Health and Medical Research Council (Australia), Abbott Diagnostic, Sanofi, Janssen Pharmaceuticals, and NSW Health; reports honorarium from CSL, CPC Clinical Research, Sanofi, Boehringer-Ingelheim, Heart Foundation, and Abbott; serves as Board Director for the Australian Cardiovascular Alliance, Executive Committee Member for CPC Clinical Research, Founding Director and CMO for Prokardia and Kardiomics, and Executive Committee member for the CAD Frontiers A2D2 Consortium. In addition, G.A.F serves as Chief Medical Office of the nonprofit, CAD Frontiers, with industry partners including Novartis, Amgen, Siemens Healthineers, ELUCID, Foresite Labs LLC, HeartFlow, Cleerly, Caristo, Genetech, Artyra, Bitterroot Bio, and Allelica. G.A.F. reports the following patents: “Patent Biomarkers and Oxidative Stress” awarded May 2017 (US9638699B2), issued to Northern Sydney Local Health District; “Use of P2X7R antagonists in cardiovascular disease” (PCT/AU2018/050905), licensed to Prokardia; “Methods for treatment and prevention of vascular disease” (PCT/AU2015/000548), issued to The University of Sydney/Northern Sydney Local Health District; “Wound healing methods” (PCT/AU2022/050129), issued to The University of Sydney; “Wound healing compositions” (PCT/AU2022/050130), issued to The University of Sydney; “Methods for predicting coronary artery disease” (AU202290266), issued to The University of Sydney; and “Novel P2X7 Receptor Antagonists” (PCT/AU2022/051400 [November 23, 2022], International Application No. WO/2023/092175 [June 1, 2023]), issued to The University of Sydney. M.F reports support from the National Institutes of Health, Alleviant, Gradient, Reprieve, Sardocor, and Doris Duke; and is a consultant/has ownership interest in Abbott, Alleviant, xonTherapies, Merck, and NovoNordisk. A.P. has received research support from the National Institute of Health, American Heart Association, Applied Therapeutics, Roche, Ultromics, and ScPharmaceuticals; has received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Axon therapies, Medtronic, Edward Lifesciences, Science37, Novo Nordisk, Bayer, Merck, Sarfez Pharmaceuticals, Emmi Solutions, Anumana, Semler Scientific, Ultromics, Merck, Encarda, Kieele Health, Acorai; and has received nonfinancial support from Pfizer and Merck. A.P. is also a consultant for Palomarin with stock options. D.J.H. is supported by the Duke-NUS Signature Research Programme funded by the Ministry of Health's National Medical Research Council under its Singapore Translational Research Investigator Award (MOH-STaR21jun-0003). M.D.M. is supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd under the NMRC Clinician Scientist-Individual Research Grant (MOH-001228) and NMRC Clinician Scientist Award (MOH-001631), as well as the National Research Foundation, Singapore (NRF) under the NMRC Open Fund - Large Collaborative Grant (MOH-001325) and administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd. M.D.M is a consultant/on the advisory panel or has paid speaking engagements in Roche, Astellas, Gilead, LernaBio, Boston Scientific, Olympus Medical, and Perspectum. M.M serves as an associate editor of Circulation: Cardiovascular Interventions. A.M.R is the New Zealand Heart Foundation Chair of Cardiovascular Studies; is on the advisory board for Roche Diagnostics; receives speakers fees from Roche Diagnostics; and receives research grant support, in cash or in mind, from Roche Diagnostics, Abbott Laboratories, Sphingotec, Thermo Fisher, Astra Zeneca, and Novo Nordisk. S.J.N reports research grant support from AstraZeneca, Amgen, Anthera, Cerenis, Eli Lilly, Esperion, InfraReDx, LipoScience, The Medicines Company, New Amsterdam Pharma, Novartis, Resverlogix, Roche, and Sanofi-Regeneron; and consulting fees from Akcea, Amarin, Anthera, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Omthera, Merck, Resverlogix, Sanofi-Regeneron, Takeda, and Vaxxinity. M.Y.C receives salary support from an National Medical Council Research Clinician Scientist Award (Senior Investigator Category; No. MOH-000280-00). The other authors report no conflicts.

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