Sarcopenic Obesity Accelerates the Progression of Cardiovascular-Kidney-Metabolic Syndrome: A Longitudinal Discovery and Cross-Sectional Validation Study

Objective The specific impact of body composition phenotypes on the progression of the newly defined Cardiovascular-Kidney-Metabolic (CKM) syndrome remains under-investigated. This study aims to elucidate the independent and synergistic effects of sarcopenic obesity (SO), obesity, and sarcopenia on the longitudinal progression of CKM syndrome stages and incident cardiovascular events. Research Design and Methods We adopted a dual-cohort design combining longitudinal discovery and cross-sectional validation. The discovery cohort included 7,769 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 and multi-state Markov models were employed to estimate the risk of incident cardiovascular disease (CVD) and stage transitions. External validation was performed using data from 3,936 participants in the National Health and Nutrition Examination Survey (NHANES 2011–2018), where muscle mass was measured by dual-energy X-ray absorptiometry (DXA). Results In the longitudinal analysis, the SO phenotype was associated with the highest incidence of CVD events (29.5%). After full adjustment, participants with SO faced a significantly higher risk of incident CVD (HR: 2.07, 95% CI 1.76–2.43) compared to the Normal group, exceeding the risk for Obesity Only (HR 1.52) and Sarcopenia Only (HR 1.18). Multi-state Markov modeling revealed that SO was the strongest independent predictor of progression to higher CKM stages (OR 1.89). A significant additive interaction was observed between sarcopenia and obesity (RERI = 0.35, P = 0.027), confirming a synergistic deleterious effect. External validation in the NHANES cohort corroborated these findings, where SO was independently associated with the highest likelihood of prevalent Advanced CKM (Stage 3–4) (OR 2.04, 95% CI 1.53–2.70). Conclusion Sarcopenic Obesity acts as a high-risk, synergistic phenotype that significantly accelerates the progression of CKM syndrome, driven by a "double burden" that exceeds the additive effects of its components. Current CKM staging reliant solely on BMI may underestimate cardiovascular risk in older adults. Integrating muscle mass assessment into CKM risk stratification is essential to identify vulnerable populations and prevent irreversible disease trajectories.