Abstract
Frailty is a prevalent geriatric syndrome, but its role in cardiometabolic disease (CMD) progression remains unclear. We examined whether frailty predicted CMD transitions. We included 22,754 participants aged 50+ from the Guangzhou Biobank Cohort Study without baseline CMD. Frailty was assessed using a 35-item frailty index (FI). Cardiometabolic multimorbidity (CMM) was defined as ≥2 of type 2 diabetes, ischemic heart disease, and stroke. Cox and multistate models estimated associations of frailty with first CMD (FCMD), CMM, and mortality. During a mean follow-up of 16.4 years, 8710 developed FCMD, 2332 progressed to CMM, and 5411 died. After adjustment, multistate analyses showed that frailty accelerated transitions from health to FCMD, from FCMD to CMM, and from CMM to death (HR per 0.1 increment in FI ranging from 1.14 to 1.48). Frailty was independently associated with CMD progression and mortality. Multistate analyses highlight its dynamic role in multimorbidity, supporting routine frailty assessment in cardiometabolic prevention.