Associations of cardiovascular-kidney-metabolic syndrome with the risk and state transitions of sarcopenia: A longitudinal cohort study

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is closely associated with a wide range of adverse health outcomes, yet its relationship with sarcopenia remains poorly defined. This study aimed to investigate the association between CKM syndrome and incident sarcopenia and to further evaluate its impact on sarcopenia state transitions. METHODS: We analyzed UK Biobank data from 47,431 participants without sarcopenia at baseline and with complete CKM risk factor. Kaplan-Meier method and Cox proportional hazards models were applied to evaluate the association between CKM stages and the incidence of sarcopenia, with subgroup and sensitivity analyses conducted. Additionally, 49,905 participants with complete baseline sarcopenia assessments were included in a multi-state Markov model to estimate the impact of CKM stages on transition probabilities and intensities among non-sarcopenia, possible sarcopenia, confirmed sarcopenia, and death. RESULTS: Kaplan-Meier curves demonstrated a gradual increase in the cumulative incidence of sarcopenia with advancing CKM stages (P < 0.0001). In fully adjusted Cox regression models, CKM stage 4 was associated with higher risks of developing probable sarcopenia (HR, 1.22; 95% CI, 1.07-1.39) and confirmed sarcopenia (HR, 1.68; 95% CI, 1.02-2.77). No significant interactions were found in subgroup analyses, and sensitivity analyses supported the robustness of the findings. In the multi-state Markov model, compared with participants in CKM stage 0, those in CKM stages 2-3 and 4 had a lower hazard of recovery from possible sarcopenia to non-sarcopenia (HR 0.55; 95% CI 0.46-0.67 and HR 0.50; 95% CI 0.36-0.68, respectively). Additionally, higher CKM stages were associated with greater probabilities of progression to more severe sarcopenia states. CONCLUSIONS: In this longitudinal cohort study, more advanced CKM stages were associated with a higher risk of incident sarcopenia and with less favorable trajectories of sarcopenia state transitions. Early identification and management of CKM may help prevent the onset of sarcopenia and attenuate its progression to more severe states.