Yifeng Zhang,1,* Hui Chen,2,* Zhongli Chen,3,* Xihao Du,4 Jiawei Chen,2 Mirenuer Aikebaier,1 Shuyao Shan,1 Ling Yang,2 Anqi Zhao,2 Yanping Wang,2 Yehong Liu,5 Ke Yang1 

1Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3State Key Laboratory of Cardiovascular Disease, Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Cardiology, Shanghai East Hospital Tongji University School of Medicine, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ke Yang, Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin second Road, Shanghai, 200025, People’s Republic of China, Email ykk_ykkk@126.com Yehong Liu, Department of Cardiology, Shanghai East hospital Tongji University School of Medicine, No. 150 Jimo Road, Shanghai, 200120, People’s Republic of China, Email flshch@163.com

Background: The Sarcopenia Index (SI) is a recognized predictor of cardiovascular risk in patients with coronary artery disease (CAD), yet its association with aortic valve sclerosis (AVSc) remains insufficiently studied. This study aimed to examine the relationship between SI and AVSc in CAD patients.
Methods: In this retrospective study, 1056 CAD patients at Shanghai Ruijin Hospital underwent SI assessment and Doppler echocardiography. SI was calculated as [serum creatinine (mg/dL)/cystatin C (mg/L)] × 100. Logistic regression, subgroup analyses, and restricted cubic splines evaluated the SI-AVSc association. ROC curves determined SI’s diagnostic value and its addition to traditional AVSc factors. In parallel with clinical observations, aortic valve changes were analyzed in mice via hematoxylin and eosin, AlizarinRed S, and Masson’s trichrome to assess valve thickness, fibrosis and calcification.
Results: Patients with the lowest SI levels showed a higher prevalence of AVSc. Multivariate logistic regression revealed that SI was independently associated with AVSc (P< 0.001). The C-statistic for SI in identifying AVSc was 0.708 (95% CI: 0.671, 0.744), and it improved risk stratification when SI was added to traditional clinical models (C-statistic increased from 0.840 to 0.866). In the subgroup analysis, the discriminatory power of SI was enhanced among elderly patients. Findings from animal models supported these results, and Spearman correlation analyses revealed negative correlation between SI and peak systolic aortic valve flow velocity (Spearman’s rho=− 0.578, P=0.006). Histological analysis demonstrated that aortic valve leaflets in the low SI group were thicker and more fibrotic than those in the high SI group, and this complementary approach provided mechanistic insights into how sarcopenia may promote valve degeneration in elder mice.
Conclusion: Lower Sarcopenia Index is associated with the presence of AVSc in CAD patients. SI improves risk stratification and acts as a valuable associated marker for AVSc, emphasizing its potential clinical utility in enhancing patient management.

Keywords: sarcopenia index, aortic valve sclerosis, coronary artery disease