Metabolic dysfunction associated steatotic liver disease, cardiometabolic multimorbidity and mortality: evidence from...

Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic multimorbidity (CMM) are growing public health concerns. However, the impact of MASLD on single cardiometabolic disease (CMD), CMM, and mortality remains unclear.

This prospective analysis used data from the UK Biobank, involving 376,087 participants aged 37-73 years. CMM was defined as the coexistence of at least two CMDs, including stroke, ischemic heart disease (IHD), and type 2 diabetes (T2D). MASLD severity was evaluated using liver fibrosis scores. Multivariable Cox proportional hazards model was used to investigate the associations. Structural equation modeling was employed to determine the extent to which CMD or CMM mediated the relationship between MASLD and death.

Over a median follow-up of 11.7 years, MASLD was linked to significantly higher risks of single CMD (HR 1.94, 95% CI 1.92-1.96), CMM (HR 3.40, 95% CI 3.31-3.49), and all-cause mortality (HR 1.21, 95% CI 1.20-1.23) in CMD-free participants. Additionally, MASLD increased the risk of progression from single CMD to CMM (HR 1.95, 95% CI 1.81-2.10) and to all-cause mortality (HR 1.11, 95% CI 1.03-1.20). However, MASLD was not independently associated with transitions from CMM to mortality (HR 1.06, 95% CI 0.89-1.28). Furthermore, these risks escalated with increasing MASLD severity. CMD mediated 44.5% of the indirect effect of MASLD on mortality, and CMM mediated 32.5% of this effect.

MASLD is associated with the increased risk of CMD, CMM, and mortality. Preventing and managing MASLD may reduce the incidence of CMD, CMM, and associated mortality.