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

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Emerging evidence suggests that the vascular manifestations of MASLD differ substantially between men and women. We therefore hypothesized that the mechanisms, plaque phenotypes, and clinical implications of MASLD-related ASCVD are sex-specific.

In this narrative review, we searched PubMed/MEDLINE for studies published up to April 2026 and synthesized current evidence regarding sex differences in MASLD-related atherosclerosis. Available data support a sex-specific vascular paradigm in MASLD. In men, MASLD is more strongly associated with calcified and obstructive coronary atherosclerosis. In contrast, women with MASLD more frequently exhibit non-calcified atherosclerotic phenotypes and functional vascular abnormalities (e.g., endothelial dysfunction, arterial stiffness, and coronary microvascular dysfunction). Importantly, despite lower coronary artery calcium (CAC) burden, women with MASLD experience a disproportionately greater risk of adverse cardiovascular events. Therefore, calcification-centered assessment may inadequately capture ASCVD risk in women with MASLD by failing to identify non-calcified plaque and functional vascular abnormalities. These sex differences are likely mediated by interacting pathobiological and socio-cultural factors, including sex hormones and menopausal transition, adipose tissue distribution, immune-metabolic and inflammatory profiles, genetic susceptibility, and gender influences.

MASLD is associated with distinct sex-specific cardiovascular phenotypes that have important clinical implications for ASCVD risk assessment and prevention. Women with MASLD may develop clinically significant ASCVD despite lower CAC burden, supporting a sex- and menopause-aware approach to cardiovascular evaluation. In selected high-risk women, complementary use of multimodality imaging beyond CAC may improve risk stratification and facilitate earlier detection of clinically relevant cardiovascular disease.