Association of sarcopenic obesity with advanced cardiovascular-kidney-metabolic syndrome and incident cardiovascular disease: a longitudinal and cross-sectional study.

OBJECTIVE: This study aimed to examine the associations of sarcopenic obesity, obesity only, and sarcopenia only with advanced cardiovascular-kidney-metabolic (CKM) syndrome and incident cardiovascular disease (CVD), and to assess whether sarcopenia and obesity were jointly associated with long-term cardiovascular risk. RESEARCH DESIGN AND METHODS: We adopted a dual-cohort design combining longitudinal discovery and cross-sectional validation. The discovery cohort included 7,759 participants from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018). Body composition phenotypes were classified into four groups: Normal, Obesity Only, Sarcopenia Only, and Sarcopenic Obesity (SO). Sarcopenia was defined by AWGS 2019 criteria. CKM syndrome was staged (0-4) according to the 2023 American Heart Association (AHA) Presidential Advisory. Cox proportional hazards models were used to estimate the association between body composition phenotypes and incident CVD during follow-up. In participants with complete CKM staging data at both 2011 and 2015, a descriptive 4-year observed CKM transition probability matrix was constructed to describe stage movement from 2011 to 2015. External consistency was examined using data from 3,936 participants in NHANES 2011-2018, where muscle mass was measured by dual-energy X-ray absorptiometry (DXA). RESULTS: In the CHARLS longitudinal cohort, sarcopenic obesity showed the highest cumulative incidence of CVD events (29.3%). After full adjustment, sarcopenic obesity was associated with a more than two-fold higher risk of incident CVD compared with the Normal group (HR 2.07, 95% CI 1.76-2.45), followed by Obesity Only (HR 1.51, 95% CI 1.31-1.74) and Sarcopenia Only (HR 1.23, 95% CI 1.03-1.45). A positive additive interaction between sarcopenia and obesity was observed (RERI = 0.34, P = 0.027). This association remained consistent in the restricted analysis among participants free of advanced CKM at baseline. In the descriptive four-year transition analysis, early CKM stages frequently moved toward higher-risk stages, whereas advanced stages were more persistent. In NHANES, sarcopenic obesity was associated with the highest likelihood of prevalent advanced CKM syndrome (OR 2.04, 95% CI 1.53-2.70). CONCLUSION: Sarcopenic obesity was consistently associated with a greater burden of advanced CKM and a higher risk of incident CVD in the CHARLS longitudinal cohort, with similar cross-sectional associations observed in the NHANES validation cohort. Although causal relationships cannot be established, these findings suggest that sarcopenic obesity may serve as a clinically useful phenotypic marker for identifying individuals at increased cardiometabolic risk.