Metabolic dysfunction‐associated steatotic liver disease and sex‐specific risk of fatal and non‐fatal cardiovascular events: A meta‐analysis
Mohamad Jamalinia, Fatemeh Zare, Alessandro Mantovani, Giovanni Targher, Amedeo Lonardo
Abstract
Abstract 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 ~18.5 million individuals were included (~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.