Sex differences in MASLD-related atherosclerosis: plaque phenotype, vascular dysfunction, and cardiovascular outcomes

Area of Science:

• Cardiology
• Metabolic Diseases
• Sex Differences in Medicine

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD).
• Vascular manifestations of MASLD show notable differences between males and females.
• The study hypothesizes sex-specific mechanisms, plaque phenotypes, and clinical outcomes in MASLD-related ASCVD.

Purpose of the Study:

• To review and synthesize current evidence on sex differences in MASLD-related atherosclerosis.
• To explore the distinct vascular paradigms and clinical implications of MASLD in men versus women.
• To highlight the need for sex-specific approaches in ASCVD risk assessment and prevention for MASLD patients.

Main Methods:

• A narrative review of studies indexed in PubMed/MEDLINE up to April 2026.
• Synthesis of existing data on sex-specific vascular manifestations in MASLD.
• Analysis of differences in atherosclerosis phenotypes and cardiovascular risk between men and women with MASLD.

Main Results:

• Men with MASLD show a stronger association with calcified, obstructive coronary atherosclerosis.
• Women with MASLD more frequently present with non-calcified plaques and functional vascular abnormalities.
• Women with MASLD face a disproportionately higher ASCVD risk despite lower coronary artery calcium (CAC) burden, indicating limitations of CAC-centered risk assessment.

Conclusions:

• MASLD is linked to distinct, sex-specific cardiovascular phenotypes impacting ASCVD risk assessment and prevention.
• Women with MASLD can develop significant ASCVD even with lower CAC, necessitating a sex- and menopause-aware cardiovascular evaluation.
• Multimodality imaging beyond CAC may enhance risk stratification and early detection of cardiovascular disease in high-risk women with MASLD.