ASSOCIATION BETWEEN METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE AND CARDIOVASCULAR OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growingly recognized multisystem disorder, but the relationship between MASLD and cardiovascular outcomes is not fully understood.

Objective: To comprehensively review and measure the relationship between MASLD and cardiovascular outcomes.

Methods: Longitudinal cohort studies reporting adjusted associations of MASLD, metabolic dysfunction-associated fatty liver disease (MAFLD), or non-alcoholic fatty liver disease (NAFLD) with clinical cardiovascular outcomes were included. Relative effect estimates were pooled using random-effects models. The following were assessed: heterogeneity, prediction intervals, disease-definition subgroups, sensitivity analyses, cohort overlap, and small-study effects.

Results: 19 cohort studies were selected. The composite analysis of cardiovascular disease or major adverse cardiovascular events was based on 10 independent estimates. There was an association with increased composite cardiovascular risk with steatotic liver disease (pooled relative effect 1.48, 95% CI 1.25–1.75; I²=96.9%), but the prediction interval extended beyond the null (0.82–2.68). Pooled associations were significant for MASLD (1.48, 95% CI 1.17–1.88) and MAFLD (1.62, 95% CI 1.10–2.38), but inconclusive for NAFLD (1.31, 95% CI 0.99–1.74). Increased risks were also observed for heart failure (1.46, 95% CI 1.06–2.00), myocardial infarction (1.34, 95% CI 1.13–1.58), ischemic stroke (1.14, 95% CI 1.11–1.17), and atrial fibrillation (1.17, 95% CI 1.02–1.35). There was no significant difference in cardiovascular mortality (1.35, 95% CI 0.84–2.18).

Conclusion: There was substantial heterogeneity, different definitions of the disease, and different effect measures, which should be taken into account when interpreting the association of MASLD with multiple cardiovascular outcomes.