Frailty status and mortality among patients with cardiometabolic diseases in an international multi-cohort study

Frailty is an indicator of biological aging associated with adverse outcomes in cardiometabolic diseases (CMD). We investigated the association between frailty status and mortality risk using data from five prospective cohorts including the UK Biobank, NHANES, CHARLS, ELSA, and HRS. Across these cohorts, pre-frail participants had a 21%-66% higher risk of all-cause mortality, while frail participants had a 54%-132% higher risk compared with non-frail individuals. Frailty was also associated with increased risks of cardiovascular and non-cardiovascular mortality, while associations with cancer-related mortality were mainly observed among individuals classified as frail. Subgroup analyses revealed heterogeneity across age, body mass index (BMI), sex, and CMD burden, with stronger associations among younger individuals (<65 years), those with lower BMI, and individuals with multiple CMDs. Sensitivity analyses yielded consistent results. These findings suggest that frailty may serve as an important prognostic marker in CMD populations and support risk stratification in clinical management.