Metabolic dysfunction-associated steatotic liver disease and sex-specific risk of fatal and non-fatal cardiovascular events: A meta-analysis

Aims: Since sex is a significant modifier of cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver disease (MASLD), we performed a meta-analysis to estimate the sex-specific risk of fatal and non-fatal CVD events in adults with MASLD.Materials and Methods: We searched four major electronic databases from inception to November 2024 to identify observational cohort studies examining sex-specific associations between MASLD and the risk of fatal and/or non-fatal CVD events. The diagnosis of MASLD and its severity were assessed using serum biomarkers/scores, International Classification of Diseases codes, imaging or histology.Results: Thirty-six cohort studies with aggregate data on similar to 18.5 million individuals were included (similar to 25% with MASLD; 48% women; mean age of 50.2 years). During a median follow-up of 6.9 years (IQR 5.0-12.3), approximately 515 000 fatal and/or non-fatal CVD events occurred (42% in women). MASLD was associated with a higher risk of fatal or non-fatal CVD events in women (pooled hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.44-1.75; I-2 = 96.10%) than in men (pooled HR 1.37, 95% CI 1.27-1.48; I-2 = 96.26%) (p-value for sex difference = 0.018). The severity of MASLD (variably assessed) further increased the magnitude of this risk, especially in women (pooled HR 2.40, 95% CI 1.73-3.32; I-2 = 57.29%). Sensitivity analyses did not modify these findings. The funnel plot and Egger's test showed no significant publication bias.Conclusions: Women with MASLD are at higher risk of incident fatal and non-fatal CVD events compared with men, especially as the severity of MASLD increases. These findings emphasize the necessity for sex-specific CVD risk assessment and management strategies.