Cardiovascular Risk in Women with Metabolic Dysfunction-Associated Steatotic Liver Disease Across the Menopausal Transition

AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a substantial global health burden, yet the cardiovascular impact across menopausal status remains unclear. Thus, this study aimed to assess the association between MASLD and cardiovascular risk in premenopausal and postmenopausal women. METHODS AND RESULTS: We conducted a nationwide population-based cohort study using the Korean National Health Insurance Service database. Women aged 40 years or older were categorized by the fatty liver index as having no MASLD (<30), grade 1 (30-59), or grade 2 (≥60). The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction, ischemic stroke, and cardiovascular death. Among 1,931,330 women aged 40 years or older, including 837,363 premenopausal and 1,093,967 postmenopausal women, MACE incidence (per 1,000 person-years) increased with MASLD severity: 1.82, 2.93, and 3.91 in premenopausal women, and 7.68, 10.55, and 12.36 in postmenopausal women. 5-year absolute MACE risks also rose with MASLD severity: premenopausal (0.45% [95% CI 0.44%-0.47%], 0.65% [95% CI 0.62%-0.68%], 0.87% [95% CI 0.82%-0.93%]) and postmenopausal (2.74% [95% CI 2.71%-2.77%], 3.25% [95% CI 3.20%-3.30%], 3.83% [95% CI 3.75%-3.91%]). Absolute risk differences between no MASLD and grades 1 or 2 were over twice as large in postmenopausal women (0.51% [95% CI 0.47%-0.55%] and 1.09% [95% CI 1.02%-1.17%]) than in premenopausal women (0.20% [95% CI 0.17%-0.22%] and 0.42% [95% CI 0.37%-0.47%]). CONCLUSION: MASLD was associated with increased cardiovascular risk in both premenopausal and postmenopausal women. The absolute excess risk associated with MASLD was larger in postmenopausal women. These findings emphasize incorporating hepatic steatosis severity and menopausal status into cardiovascular risk assessment and prevention strategies for women's health.