The association of frailty with cardiovascular diseases and mortality in metabolic dysfunction-associated steatotic liver disease

Frailty is highly prevalent in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the extent to which frailty influences cardiovascular disease (CVD) incidence, cardiovascular mortality, and all-cause mortality in MASLD individuals remains poorly understood. This study aimed to evaluate the impact of frailty on cardiovascular outcomes and mortality in this population. A total of 193,942 participants without prior CVD from the UK Biobank were included. Participants were categorized into three groups based on frailty phenotype: non-frailty, pre-frailty, and frailty. MASLD was defined as hepatic steatosis accompanied by at least one cardiometabolic abnormality. The primary outcome was CVD incidence, with secondary outcomes including cardiovascular and all-cause mortality. After multivariate adjustment, the risk of CVD was higher in MASLD participants with pre-frailty (HR 1.08, 95% CI 1.05–1.12) and frailty (HR 1.41, 95% CI 1.33–1.49) than in those with non-frailty. The association of frailty with CVD was strongest in participants with MASLD and advanced fibrosis (HR 2.60, 95% CI 2.04–3.30), intermediate in MASLD without fibrosis (HR 1.73, 95% CI 1.63–1.84), and weakest in non-MASLD (HR 1.58, 95% CI 1.47–1.70). Similar results were also observed for cardiovascular mortality. Furthermore, among the five components of frailty phenotype, slow gait speed demonstrated the strongest associations with the risks of CVD incidence in MASLD, cardiovascular mortality, and all-cause mortality. Frailty was associated with increased risks of CVD incidence, cardiovascular mortality, and all-cause mortality among individuals with MASLD, particularly those with a higher fibrosis burden as defined by FIB-4.