Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Nov;42(4):455-464.
doi: 10.1055/a-1930-6658. Epub 2022 Aug 25.

Shared Mechanisms between Cardiovascular Disease and NAFLD

Daniel Q Huang  1   2   3 , Michael Downes  4 , Ronald M Evans  4 , Joseph L Witztum  5 , Christopher K Glass  6   7 , Rohit Loomba  1   8
Affiliations
Review

Shared Mechanisms between Cardiovascular Disease and NAFLD

Daniel Q Huang et al. Semin Liver Dis. 2022 Nov.

Abstract

The burden of nonalcoholic fatty liver disease (NAFLD) is rising globally. Cardiovascular disease is the leading cause of death in patients with NAFLD. Nearly half of individuals with NAFLD have coronary heart disease, and more than a third have carotid artery atherosclerosis. Individuals with NAFLD are at a substantially higher risk of fatal and nonfatal cardiovascular events. NAFLD and cardiovascular disease share multiple common disease mechanisms, such as systemic inflammation, insulin resistance, genetic risk variants, and gut microbial dysbiosis. In this review, we discuss the epidemiology of cardiovascular disease in NAFLD, and highlight common risk factors. In addition, we examine recent advances evaluating the shared disease mechanisms between NAFLD and cardiovascular disease. In conclusion, multidisciplinary collaborations are required to further our understanding of the complex relationship between NAFLD and cardiovascular disease and potentially identify therapeutic targets.

PubMed Disclaimer

Conflict of interest statement

R.L. serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals, and Viking Therapeutics. In addition, his institutions received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Merck, Pfizer, Sonic Incytes, and Terns Pharmaceuticals. Co-founder of LipoNexus Inc.D.H. receives funding support from Singapore Ministry of Health's National Medical Research Council under its NMRC Research Training Fellowship (MOH-000595–01). In addition, he has served as an advisory board member for Eisai.J.L.W. holds patents related to the use of oxidation specific antibodies held by UCSD. He is cofounder of Oxitope and Kleanthi Diagnostic and is a consultant to Ionis Pharmaceuticals.

Figures

Fig. 1
Fig. 1
Estimated global prevalence of coronary heart disease, by World Health Organization (WHO) region.
Fig. 2
Fig. 2
Established shared risk factors between nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease.
Fig. 3
Fig. 3
Putative shared disease mechanisms between cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). In NAFLD, there is increased production of proinflammatory cytokines, which promotes atherosclerosis. Individuals with NAFLD and cardiovascular disease have endothelial dysfunction, which may be mediated by early atherosclerosis. Insulin resistance is a key driver of both NAFLD and cardiovascular disease. With more advanced hepatic and cardiovascular disease, there is increased abundance of proinflammatory Gram-negative bacteria in both NAFLD and cardiovascular disease. Genetic variants in PNPLA3 and TM6SF2 promote hepatic steatosis and advanced fibrosis but reduce systemic lipid levels and may be cardioprotective.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64(01):73–84 - PubMed
    1. Le MH, Yeo YH, Li X, et al. Global NAFLD prevalence - a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2021; S1542-3565(21)01280–5 - PubMed
    1. Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell 2021;184(10):2537–2564 - PubMed
    1. Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 2013;10(11):686–690 - PubMed
    1. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2021;18(04):223–238 - PMC - PubMed

Publication types

MeSH terms