Hepatic Steatosis Is Associated With Increased Cardiovascular Risk Through Adverse Coronary Plaque Composition

Brendel, Jan M. and Mayrhofer, Thomas and Kerkovits, Nóra M. and Kolossváry, Márton and Ersözlü, Sara and Alhanti, Brooke and Corey, Kathleen E. and Pagidipati, Neha and Shah, Svati H. and Meyersohn, Nandini M. and Ferencik, Maros and Lu, Michael T. and Lamon-Fava, Stefania and Hoffmann, Udo and Douglas, Pamela S. and Foldyna, Borek (2026) Hepatic Steatosis Is Associated With Increased Cardiovascular Risk Through Adverse Coronary Plaque Composition. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY. ISSN 1542-3565 (In Press)

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Abstract

Background & Aims: Hepatic steatosis has been associated with major adverse cardiovascular events independently of other cardiovascular risk factors and the severity of coronary artery disease. Nevertheless, the relationship between hepatic steatosis, coronary plaque composition, and major adverse cardiovascular events remains unclear. Methods: A central core laboratory analyzed Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) participants randomized to the computed tomography arm. Hepatic steatosis was assessed on noncontrast computed tomography using standard hepatic and splenic attenuation methods. Coronary computed tomography angiography was used to quantify total, calcified, noncalcified, and low-attenuation plaque volume and burden (% vessel volume). Multivariable regression and mediation analyses assessed relationships between hepatic steatosis, plaque components, and major adverse cardiovascular events (death, myocardial infarction, unstable angina hospitalization). The median follow-up was 25 months (interquartile range, 18–33 months). Results: Among 3637 patients (age, 60.6 ± 8.2 years; 51.4% female), 25.5% had hepatic steatosis and were slightly younger, more often male, had more cardiovascular risk factors, and had a higher rate of major adverse cardiovascular events (4.1% vs 2.5%) (all P < .05). After adjustment for clinical risk factors, hepatic steatosis was associated with greater noncalcified plaque burden (β, 0.15%; 95% confidence interval, 0.04–0.27; P = .008). Hepatic steatosis was associated with increased risk of major adverse cardiovascular events independent of atherosclerotic cardiovascular disease risk score, obesity, obstructive stenosis, and noncalcified plaque burden (adjusted hazard ratio, 1.69; 95% confidence interval, 1.12–2.54; P = .012), whereas noncalcified plaque burden mediated 11% of the association between hepatic steatosis and major adverse cardiovascular events. Conclusions: Hepatic steatosis was associated with greater noncalcified plaque burden and increased risk of major adverse cardiovascular events, with noncalcified plaque burden accounting for a portion of this association, suggesting a link between hepatic steatosis and vulnerable coronary atherosclerosis. These findings support integrated cardiometabolic risk assessment in patients undergoing coronary computed tomography angiography.

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