Sarcopenia risk along the cardiovascular-kidney-metabolic syndrome spectrum: synergistic effects of multisystem burden and physical inactivity

Sarcopenia is a progressive skeletal muscle disorder that contributes to disability, chronic disease burden, and mortality. While the roles of metabolic, cardiovascular, and kidney dysfunction are individually recognized, the collective influence of cardiovascular-kidney-metabolic (CKM) syndrome on sarcopenia remains uncharacterized. Furthermore, it is unclear whether physical inactivity amplifies this risk. This study is the first to apply the recently defined CKM staging framework to investigate sarcopenia risk, thereby offering an integrated, multisystem perspective. A cross-sectional analysis was conducted using 4,193 adults from the National Health and Nutrition Examination Survey 2011–2018 dataset. Sarcopenia was defined using the Foundation for the National Institutes of Health criteria. CKM syndrome was classified into five progressive stages (0–4), and physical activity was quantified using metabolic equivalent of task scores. Multivariable logistic regression models assessed the independent and combined associations of CKM stage and physical inactivity with sarcopenia, adjusting for demographic and clinical confounders. Subgroup and interaction analyses explored effect modification. The overall prevalence of sarcopenia was 7.2%. Sarcopenia prevalence increased progressively across CKM stages, with the highest risk in advanced stages. CKM Stage 2 (OR = 1.58, 95% CI: 1.03–2.43, p = 0.037) and Stages 3–4 (OR = 3.51, 95% CI: 1.54–8.01, p = 0.003; p for trend < 0.001) were independently associated with sarcopenia. Physical inactivity further elevated sarcopenia risk (OR = 2.16, 95% CI: 1.56-3.00, p < 0.001). Joint analysis revealed a striking synergistic effect: individuals who were both physically inactive and in CKM Stages 3–4 had over sevenfold greater odds of sarcopenia compared to active individuals in Stage 0–1 (OR = 7.62, 95% CI: 3.02–19.21; p for trend < 0.001). Marital status significantly modified these associations (p for interaction = 0.038). This study provides the first evidence linking CKM syndrome stages with sarcopenia risk and identifies a potent interaction with physical inactivity. These findings advance the conceptualization of sarcopenia as a multisystem disorder and underscore the importance of integrated lifestyle and disease management strategies to mitigate muscle loss in vulnerable populations.