Association of sarcopenia and longitudinal changes in sarcopenia status with all-cause mortality in individuals with cardiovascular-kidney-metabolic syndrome

We investigated the associations of sarcopenia, handgrip strength (HGS), appendicular skeletal muscle mass index (ASMI), and longitudinal changes in sarcopenia status with all-cause mortality among middle-aged and older adults aged ≥ 50 years with cardiovascular-kidney-metabolic (CKM) syndrome. This prospective cohort study included 6,601 participants with CKM syndrome from the China Health and Retirement Longitudinal Study (CHARLS), of whom 454 had sarcopenia at baseline. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2025 criteria. Cox proportional hazards models and restricted cubic splines were used to examine the associations of sarcopenia, HGS, and ASMI with all-cause mortality. Joint associations across CKM stages were further evaluated. Longitudinal analyses of changes in sarcopenia status were conducted among 4,842 participants with repeated assessments. During a mean follow-up of 8.75 ± 1.34 years, 251 deaths occurred. Sarcopenia was associated with an increased risk of all-cause mortality (HR, 2.098; 95% CI, 1.501–2.932). Higher HGS was consistently associated with lower mortality risk, with each 1-kg increase corresponding to a 4.2% lower risk of death (HR, 0.958; 95% CI, 0.941–0.974), whereas ASMI was not significantly associated with mortality after full adjustment. Compared with early CKM without sarcopenia, mortality risk was higher in early CKM with sarcopenia (HR, 3.394; 95% CI, 1.766–6.523), advanced CKM without sarcopenia (HR, 1.722; 95% CI, 1.152–2.575), and advanced CKM with sarcopenia (HR, 3.443; 95% CI, 2.099–5.649). In longitudinal analyses, incident or persistent sarcopenia was associated with increased mortality risk (HR, 2.572; 95% CI, 1.096–6.038). Among adults with CKM syndrome, sarcopenia was associated with increased all-cause mortality, and HGS was more consistently associated with mortality than ASMI. Assessment of muscle strength may complement CKM staging for mortality risk stratification. Not applicable.