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.