Advanced Cardiovascular-Kidney-Metabolic Syndrome Increases Sarcopenia Risk

The risk of sarcopenia increases with advancing cardiovascular-kidney-metabolic (CKM) syndrome stage, according to new research.1

These findings suggest clinicians can use CKM syndrome staging as a predictor for sarcopenia, extending a framework previously used to predict cardiovascular and renal outcomes.1

In 2023, the American Heart Association issued a presidential advisory for CKM staging to reflect the pathophysiology, spectrum of risk, and opportunities for prevention and care optimization within CKM syndrome. CKM was classified into 5 progressive stages (0-4).2

“​​By applying the CKM framework to sarcopenia for the first time, this study provides novel insight into the systemic nature of muscle loss and identifies high-risk groups who may benefit most from targeted lifestyle and clinical interventions,” wrote study investigator Bin Lin, postdoctoral researcher and assistant professor in the department of nephrology at The First Affiliated Hospital in China, and colleagues. “Our findings aim to inform the development of integrated preventive strategies in cardiology, nephrology, and metabolic care.”1

Investigators conducted a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) from 2011-2018 to assess the independent and combined associations of CKM stage and physical activity with sarcopenia.1

They defined sarcopenia using the Foundation for the National Institutes of Health criteria, and physical activity was assessed using the Global Physical Activity Questionnaire from the World Health Organization (WHO).1

The study included 4193 adults ≥ 18 years of age with sufficient data to define CKM syndrome stages and sarcopenia. The prevalence of sarcopenia was 7.2%. Participants with sarcopenia were significantly older (P <.001), had increased instances of hypertension (35% vs 22%), and physical inactivity (47% vs. 29%) compared to those without.1

The majority of participants were in CKM Stage 2 (60%), followed by Stage 1 (23%), Stage 0 (12%), and Stages 3 and 4 (2% each). Individuals with sarcopenia were disproportionately concentrated in advanced CKM stages; specifically, only 1% were in CKM Stage 0. In the sarcopenia group, 5% and 8% were in Stages 3 and 4, respectively, compared to 1% and 3% in the non-sarcopenia group.1

Upon multivariable logistic regression analyses, investigators noted an independent association of both physical inactivity and advancing CKM stage with increased odds of sarcopenia. Compared to their active counterparts, inactive individuals had >2 times the odds of sarcopenia (Odds Ratio [OR], 2.16; 95% Confidence Interval [CI], 1.56–3.00; P <.001).1

Lin and colleagues noted a clear dose-response relationship with the odds of sarcopenia and CKM syndrome stage. Compared with Stage 0-1, risk was increased in Stage 2 (OR, 1.58; 95% CI, 1.03-2.43) and increased further in Stages 3-4 (OR, 3.51; 95% CI, 1.54–8.01).1

“Our results highlight the importance of screening for muscle health in the management of cardiometabolic and renal disease and point to physical activity as a promising modifiable target to mitigate sarcopenia risk,” concluded investigators. “Future longitudinal and interventional studies are warranted to establish causality and test tailored prevention strategies in individuals with high CKM burden.”1

References

1. Zhang M, Fan Q, Yu J, et al. Sarcopenia risk along the cardiovascular-kidney-metabolic syndrome spectrum: synergistic effects of multisystem burden and physical inactivity. BMC Public Health. Published online December 7, 2025. doi:https://doi.org/10.1186/s12889-025-25740-3

2. Ndumele CE, Janani Rangaswami, Chow SL, et al. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023;148(20). doi:https://doi.org/10.1161/cir.0000000000001184