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Anqi Zhao,1,&ast; Ling Yang,1,&ast; Qing Zha,1,&ast; Junfeng Zhang,1 Huili Zhang,1 Zhengde Tang,1 Yanping Wang,1 Jiawei Chen,1 Ke Yang,2 Yan Liu,1 Jiateng Sun3 1Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Liu, Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of China, Tel +86 21 23271699, Fax +86 21 63136856, Email liuyan_ivy@126.com Jiateng Sun, Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, People’s Republic of China, Tel/Fax +86 21 68383477, Email sun_jiateng@126.comPurpose: The Sarcopenia Index (SI), derived from the serum creatinine to cystatin C ratio, is a potential biomarker for cardiovascular disease (CVD). However, its prognostic significance for incident CVD in aging Chinese populations remains insufficiently characterized, despite established links between sarcopenia and CVD progression.Patients and Methods: This prospective cohort study utilized data from the China Health and Retirement Longitudinal Study (CHARLS). A total of 4979 participants aged > 45 years without prevalent CVD at baseline were included (mean age 58.0 years). Participants were categorized into Sarcopenia Index (SI) tertiles as follows: Q1 (SI ≤ 71.10), Q2 (71.10 < SI ≤ 84.75), and Q3 (SI > 84.75). Incident CVD events were assessed over a 9-year follow-up period. Multivariable Cox proportional hazards models, adjusted for demographic factors, comorbidities, and lipid profiles, were employed to evaluate associations. Restricted cubic spline (RCS) analysis was used to evaluate the dose-response relationship between SI and CVD risk.Results: In the total population, the cumulative incidence of CVD was 23.5%. The lowest SI tertile (Q1) exhibited the highest cumulative CVD incidence (27.0%), compared to Q2 (23.2%) and Q3 (20.4%). After multivariable adjustment, individuals in Q1 showed a significantly increased risk of CVD compared to those in Q3 (HR: 1.249, 95% CI: 1.054, 1.478, P=0.010). RCS analysis confirmed a non-linear inverse association between SI and CVD risk (P for non-linearity = 0.003). Significant associations were particularly pronounced in males, current smokers, non-drinkers, urban residents, individuals with body mass index (BMI) ≥ 28 kg/m2, and participants without hypertension or diabetes (all P < 0.05).Conclusion: Reduced SI independently predicts elevated CVD risk in aging adults, underscoring its potential as an accessible, cost-effective screening biomarker. Integration of SI into routine clinical assessments may enhance early risk stratification and guide targeted preventive strategies, particularly for high-risk subgroups.Keywords: sarcopenia index, cardiovascular disease, CHARLS, aging, cardiovascular events