Associations of General and Central Obesity with Cardiovascular Risk by Menopausal and MASLD Status

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence increases during the menopausal transition, yet its interaction with obesity phenotypes in influencing cardiovascular disease (CVD) risk remains unclear. We examined how MASLD and obesity types are associated with CVD risk in pre- and postmenopausal women. Methods: This nationwide cohort analyzed 1,959,367 Korean women aged ≥40 years (848,672 premenopausal, 1,110,695 postmenopausal) followed for a median of 12.3 years. MASLD was defined by the fatty liver index plus ≥1 cardiometabolic risk factor and alcohol intake <20 g/day. General obesity was defined as body mass index ≥25 kg/m² and central obesity as waist circumference ≥85 cm. Results: During follow-up, 106,792 women (5.45%) developed CVD. MASLD was associated with higher CVD risk regardless of menopausal status, though the association was numerically smaller in postmenopausal women. Among women without MASLD, general obesity was associated with risk before menopause (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 1.04-1.17; central obesity, aHR 1.06, 95% CI 0.96-1.18), whereas after menopause central obesity was associated with risk (aHR 1.08, 95% CI 1.05-1.10). In postmenopausal women with MASLD, the estimate for general obesity was inverse (aHR 0.95) while central obesity remained positively associated (aHR 1.05); in an exploratory sensitivity analysis using an anthropometry-free metabolic proxy (the triglyceride-glucose index), the inverse estimate was not reproduced (aHR 1.06). Conclusions: MASLD was associated with elevated CVD risk across menopausal stages. Associations with obesity phenotype varied by menopausal status: general obesity was associated with risk in premenopausal women without MASLD, whereas after menopause the association was more consistent for central obesity. These are observational contrasts between groups that also differ substantially in age and should not be interpreted causally. They may nonetheless inform prevention tailored to menopausal stage, MASLD status, and obesity phenotype.