The relationship between sarcopenia and all–cause and cardiovascular mortality risk among middle–aged and older adults across stages 0–3 of cardiovascular–kidney–metabolic syndrome: evidence from NHANES and CHARLS

Background: Sarcopenia has been proved to be associated with cardiovascular diseases, chronic kidney disease, and metabolic disorders, but the relationship between sarcopenia and all–cause and cardiovascular mortality risk among middle–aged and older adults across stages 0–3 of cardiovascular–kidney–metabolic (CKM) syndrome remains unclear. Purpose: To investigate the relationship between sarcopenia and all–cause and cardiovascular mortality risk among middle–aged and older adults across stages 0–3 of CKM syndrome based on Nutrition Examination Survey (NHANES) 2011–2018 and the China Health and Retirement Longitudinal Study (CHARLS) 2011–2020. Methods: Multivariable Cox regression analysis was performed to analyze the association of sarcopenia with all-cause and cardiovascular disease (CVD) mortality. Restricted cubic spline (RCS) analysis was conducted to explore the non–linear relationship between body mass index (BMI)-adjusted muscle mass (appendicular skeletal muscle mass divided by BMI, ASMI) and all–cause and CVD mortality, and machine learning (ML) models were developed for mortality risk prediction. The CHARLS database was utilized as validation to enhance the stability of the results. Results: Over an average follow–up of 5.11 years, NHANES recorded 85 all–cause deaths and 12 CVD deaths. After the full adjustment, sarcopenia was significantly associated with all–cause mortality (weighted HR = 3.428, 95% CI 1.484-7.915, P = 0.004) and CVD mortality (weighted HR = 1.070, 95% CI 1.009-1.570, P = 0.049). RCS analysis revealed a nonlinear negative relationship between ASMI and CVD mortality (P for nonlinear = 0.009). ML models demonstrated robust predictive performance, with random forest (AUC=0.766) achieving the highest accuracy. In the CHARLS cohort, sarcopenia significantly increases all–cause mortality (HR = 2.519, 95% CI 1.402-4.527, P < 0.001), and subgroup analysis reported consistent results with the main analysis, Conclusion: Sarcopenia is significantly associated with all–cause and CVD mortality, and exhibits robust predictive performance for mortality among middle-aged and older individuals within CKM stages 0–3.