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Original Article Cardiovascular Risk/Epidemiology Normalized Creatinine-to-Cystatin C Ratio and Risk of Cardiometabolic Multimorbidity in Middle-Aged and Older Adults: Insights from the China Health and Retirement Longitudinal Study
Honglin Sun,*orcid , Zhenyu Wu,*orcid , Guang Wangorcid , Jia Liuorcid

DOI: https://doi.org/10.4093/dmj.2024.0100 [Epub ahead of print]
Published online: January 20, 2025
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Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
Corresponding author:  Guang Wang,
Email: wangguangcy@ccmu.edu.cn
Jia Liu,
Email: liujia0116@126.com
*These authors contributed equally to this work.
Received: 2 May 2024   • Accepted: 15 November 2024

Background
Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort.
Methods
This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed.
Results
During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders.
Conclusion
High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

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Sun H, Wu Z, Wang G, Liu J. Normalized Creatinine-to-Cystatin C Ratio and Risk of Cardiometabolic Multimorbidity in Middle-Aged and Older Adults: Insights from the China Health and Retirement Longitudinal Study. Diabetes Metab J. 2025 Jan 20. doi: 10.4093/dmj.2024.0100. Epub ahead of print.
Received: May 02, 2024; Accepted: Nov 15, 2024
DOI: https://doi.org/10.4093/dmj.2024.0100.

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