Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 27, 2020; 12(7): 378-388
Published online Jul 27, 2020. doi: 10.4254/wjh.v12.i7.378
Non-alcoholic steatohepatitis and the risk of myocardial infarction: A population-based national study
Sara Ghoneim, Aneesh Dhorepatil, Aun Raza Shah, Ganesh Ram, Subhan Ahmad, Chang Kim, Imad Asaad
Sara Ghoneim, Aneesh Dhorepatil, Aun Raza Shah, Subhan Ahmad, Chang Kim, Department of Internal Medicine, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH 44109, United States
Ganesh Ram, Department of Pain Management, The Schulich School of Medicine and Dentistry, London, Ontario N6A 5C1, Canada
Imad Asaad, Division of Gastroenterology, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH 44109, United States
Author contributions: Ghoneim S, Dhorepatil A, Shah AR, Ram G, and Asaad I designed the research; Ghoneim S, Dhorepatil A, Shah AR, Ram G, Ahmad S and Kim C performed the research; Kim C analyzed the data; Ghoneim S, Dhorepatil A, Shah AR, Ram G, Asaad A wrote the paper; All authors provide approval for the final version to be published.
Institutional review board statement: This study is exempt from Case Western Reserve/Metrohealth Medical Center IRB approval as the dataset used by Explorys database is de-identified.
Informed consent statement: Informed consent was not required for this study, as it is exempt from IRB approval because the data set used in the database is de-identified.
Conflict-of-interest statement: All authors have no conflict of interest and nothing to disclose.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sara Ghoneim, MD, Doctor, Department of Internal Medicine, Case Western Reserve University at MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109, United States. saragho@gmail.com
Received: January 11, 2020
Peer-review started: January 11, 2020
First decision: April 18, 2020
Revised: May 25, 2020
Accepted: June 10, 2020
Article in press: June 10, 2020
Published online: July 27, 2020
ARTICLE HIGHLIGHTS
Research background

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States. The severity of NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. Recent evidence suggests that the diagnosis of NAFLD may be associated with an increased risk of cardiovascular disease (CVD) independent of traditional risk factors. We believe that patients with non-alcoholic steatohepatitis (NASH) are at a higher risk of serious cardiovascular events such as myocardial infarction (MI).

Research motivation

There is an overlap between the risk factors that give rise to NAFLD and CVD. NASH remains underdiagnosed in the general population as tissue analysis is needed for accurate diagnosis. It is a more severe subtype of NAFLD associated with hepatic and systemic inflammation. Inflammation is implicated in the pathogenesis of atherosclerosis. Whether NASH is associated with serious cardiovascular events such as MI has major economic and public health implications.

Research objectives

The aim of this study was to assess the prevalence of acute MI among patients with NASH and to investigate the contribution of age and gender on the relative risk of MI in a large cohort of subjects in the United States.

Research methods

This was a large retrospective study that included over 50 million patients from over 50 states in the United States. Patients diagnosed with NASH between 1999-2019 and those with acute MI within 2018-2019 were identified. Traditional risk factors associated with both diseases were also collected. Univariable and multivariable analyses were performed to assess the association between NASH and MI.

Research results

After adjusting for traditional risk factors, there was an independent associated between NASH and MI (1.5, 95%CI: 1.40-1.62, P < 0.0001). The relative risk of MI in patients with NASH appeared to be the highest in the younger patient population (< 49 years old, RR 10.1, P < 0.0001) suggesting inflammation might be the driving force for this observation. Women with NASH had a higher relative risk of MI compared to their male counterparts (15.8 vs 11.6, P < 0.0001, respectively). Overall, the absolute risk of MI was higher in the older population.

Research conclusions

Acute MI is a prevalent diagnosis among patients with NASH. According to our dataset, NASH continues to be underdiagnosed in the United States population. Systemic inflammatory cascades are exaggerated in NASH and might be implicated in the pathogenesis of arthrosclerosis. Identification of NAFLD patients at high risk of NASH might allow for primary prevention and aggressive cardiovascular risk modification.

Research perspectives

Performing large scale prospective studies with long-term follow-up are needed to gain mechanistic insight into the pathology of NASH-MI axis.