Muscle health and cardiovascular risk across stages of Cardiovascular-Kidney-Metabolic syndrome: A prospective cohort study.

BACKGROUND: Cardiovascular-Kidney-Metabolic (CKM) syndrome represents a progressive cardiometabolic continuum. Whether the association between skeletal muscle health and cardiovascular risk is consistent across CKM stages remains unclear. METHODS: We analyzed 8405 adults free of cardiovascular disease from the China Health and Retirement Longitudinal Study (CHARLS). Upper-limb muscle health was assessed using relative handgrip strength (RGS), and lower-limb muscle health using the five-time chair stand test (5-CST). Ordinal logistic regression was used to assess CKM stage severity. Multivariable Cox models and stage-stratified analyses were used to evaluate associations with incident cardiovascular disease (CVD). Continuous and restricted cubic spline analyses were performed as secondary analyses. RESULTS: Reduced upper-limb muscle health was associated with greater CKM severity at baseline (adjusted OR 1.77, 95% CI 1.40-2.25; P < 0.001). Lower-limb muscle health showed a weaker association that attenuated after adjustment (adjusted OR 1.06, 95% CI 0.96-1.21; P = 0.182). During a median follow-up of 9 years, 1802 incident CVD events occurred. Importantly, stage-stratified analyses revealed stage-dependent associations for both measures: among individuals with nonadvanced CKM (stages 0-2), normal upper-limb muscle health was associated with a lower risk of incident CVD (HR 0.80, 95% CI 0.72-0.89; P < 0.001; P for interaction = 0.019), and normal lower-limb muscle health showed a similar inverse association with incident CVD (HR 0.78, 95% CI 0.70-0.87; P < 0.001; P for interaction =0.004). The corresponding estimates in CKM stage 3 were attenuated and less precise. Continuous and spline analyses showed broadly similar stage-specific patterns. CONCLUSIONS: Muscle health was associated with incident CVD predominantly among participants with nonadvanced CKM, indicating heterogeneity across CKM stages.