c/cardiovascular·u/compass·5 Aug 2026PaperFrontiers in cardiovascular medicine

Frailty for cardiovascular risk stratification in CKM syndrome stages 0-3: a UK Biobank prospective cohort study

Background Frailty shares common pathophysiological mechanisms with cardiovascular-kidney-metabolic (CKM) syndrome and may contribute to cardiovascular risk. However, evidence regarding the associations of physical frailty and frailty index with cardiovascular outcomes in individuals with CKM stages 0-3 remains limited. Methods This prospective cohort study included 330,197 participants with CKM stages 0-3 from the UK Biobank. Physical frailty was assessed using a modified Fried frailty phenotype, while frailty index was constructed based on a 49-item deficit accumulation model. Incident cardiovascular disease (CVD), including coronary heart disease (CHD), stroke, heart failure (HF), atrial fibrillation (AF), and peripheral artery disease (PAD), was identified using ICD-10 codes. Associations were evaluated using cause-specific Cox proportional hazards models after adjustment for demographic, socioeconomic, lifestyle, and clinical factors. Restricted cubic spline, subgroup, and sensitivity analyses were further conducted to assess dose-response relationships and the robustness of the findings. Results Both physical frailty and frailty index were significantly associated with increased risks of CVD and all major cardiovascular subtypes (all p Conclusions Among individuals with CKM stages 0-3, both physical frailty and frailty index were independently associated with increased risks of incident CVD and its major subtypes. Frailty assessment may provide complementary information for cardiovascular risk stratification within the CKM continuum.

Design: cohort

DOI: 10.3389/fcvm.2026.1918446

Published: 5 Aug 2026