Rapid progression of cardiovascular-kidney-metabolic syndrome drives accelerated frailty trajectories: A longitudinal cohort study.

The impact of dynamic cardiovascular-kidney-metabolic (CKM) syndrome progression on longitudinal frailty trajectories remains unclear. This study investigated how rapid CKM worsening influences adverse frailty index development. We analyzed 3090 community-dwelling adults (baseline CKM stages 1-3, non-frail). CKM progression over 4 years was categorized as stable/improved, mild (+1 stage), or rapid (≥2 stages). Growth mixture modeling identified latent frailty index trajectories over a 7-year follow-up. Growth mixture modeling identified 2 trajectories: "Stable Progressive" (93.5%) and "Accelerated Adverse" (6.5%). Multivariable analysis revealed that rapid CKM progression significantly increased the risk of the "Accelerated Adverse" trajectory (OR = 2.44; 95% CI: 1.56-3.83) compared to the stable/improved group. Notably, mild progression showed no significant association. Rapid CKM stage deterioration independently predicts accelerated frailty worsening. Incorporating dynamic CKM changes into clinical risk assessments is crucial for preventing the transition from cardiometabolic multimorbidity to severe frailty.