Frailty and Its Progression With Cardiovascular Disease Risk With Cardiovascular-Kidney-Metabolic Syndrome Stages 1 to 3

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome encompasses the complex interplay among the cardiovascular, kidney, and metabolic systems. The influence of frailty and its progression on future cardiovascular disease (CVD) risk within CKM stages 1 to 3 remains unclear. OBJECTIVES: The purpose of this study was to investigate the association between frailty progression and CVD risk in individuals with CKM stages 1 to 3, clarifying the prognostic significance of frailty dynamics in this population. METHODS: Data were obtained from the CHARLS (China Health and Retirement Longitudinal Study). Frailty status was evaluated by the Rockwood frailty index and classified as robust, prefrail, or frail. Changes in frailty status were divided into sustained robust state, frailty progression, frailty improvement, and sustained nonrobust state. CVD was identified by self-reported physician-diagnosed heart disease or stroke. Cox proportional hazard models and subgroups analysis were used to analyze the effect of frailty and its progression on the risk of CVD. RESULTS: Among 3,616 participants, prefrail (HR: 1.63; 95% CI: 1.45-1.84) and frail groups (HR: 1.89; 95% CI: 1.57-2.28) exhibited higher CVD risk than the robust group. Participants transitioning to a nonrobust state showed increased CVD risk (HR: 1.70; 95% CI: 1.38-2.09), with the highest risk in those with sustained nonrobust status (HR: 2.35; 95% CI: 1.99-2.78). Frailty improvement did not significantly affect CVD risk (HR: 1.21; 95% CI: 0.92-1.57). CONCLUSIONS: Frailty progression and sustained nonrobust state increased CVD risk in CKM stages 1 to 3, while frailty improvement had no significant effect. Our findings highlight frailty as a key CVD risk factor, emphasizing the need for early identification and intervention.