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.
Citations
Citations to this article as recorded by
Normalized creatinine-to-cystatin C ratio and cardiovascular disease risk in populations with cardiovascular–kidney–metabolic syndrome stages 0–3: findings from a national and prospective cohort study Defei Chen, Yuhui Li, Tailin Ran, Fu Song, Zheng Yang, Weilin Tan, Qiuyi Lu, Lanxin Tang, Lining Yang, Dingqun Bai European Journal of Medical Research.2026;[Epub] CrossRef
Association between the sarcopenia index and osteoarthritis: a cross-sectional and longitudinal study Xin Cai, Tianzuo Lan, Zong Jiang, Fang Tang, Haixia Fan European Journal of Medical Research.2026;[Epub] CrossRef
Association of the triglyceride glucose-Chinese visceral adiposity index with incident cardiometabolic multimorbidity in middle-aged and older adults: a nationwide prospective cohort study Wenling Zheng, Ziyue Man, Yanping Ren, Yu Li, Xiaohong Zhu, Lan Wang, Xi Zhang, Guilin Hu, Yu Cao Cardiovascular Diabetology.2026;[Epub] CrossRef
Normalized creatinine-to-cystatin C ratio and atherosclerotic cardiovascular disease risk in the UK Biobank Xiaoyan Liu, Huizhi Zhan, Yi Ou, Yuwen Shangguan, Jingbo Zhang European Journal of Preventive Cardiology.2026;[Epub] CrossRef
Normalized creatinine-to-cystatin C ratio and risk of hypertension in middle-aged and older adults: findings from the China Health and Retirement Longitudinal Study Ke Si, Cunwei Sun, Chuanqin Shi, Yajing Huang, Jingwei Chi, Lili Xu, Yangang Wang Nutrition, Metabolism and Cardiovascular Diseases.2026; 36(8): 104705. CrossRef
Predicting cardiometabolic multimorbidity in Chinese older adults via machine learning Zhitong Li, Angxian Lü, Wenxia Ren, Wenjing Wang, Boya An, Xiaoying Fan, Yuanyuan Yan, Yajing Bai, Anqi Zhao, Ruixue Duan, Shiwei Liu Metabolism and Target Organ Damage.2026;[Epub] CrossRef
Associations of cumulative exposure and dynamic trajectories of the triglyceride–total cholesterol–body weight index with new-onset cardiometabolic multimorbidity in middle-aged and older Chinese adults: evidence from a nationwide prospective cohort study Xiao Chen, Chaochao Wang, Qi Huang, Yuan Luo, Zhe Wu, Jing Chen, Haibo Gong Cardiovascular Diabetology.2026;[Epub] CrossRef
Mendelian Randomization to Examine the Causal Effects of Cystatin on Ovarian Lesions Tianqing Yan, Lin Guo, Renquan Lu International Journal of Women's Health.2026; Volume 18: 1. CrossRef
Creatinine to cystatin C ratio is associated with kinetic gait characteristics measured by a wearable sensor system in older adults: a cross-sectional study Lu Xu, Ji Shen, Yushan Zhang, Yuting Kang, Qiang Gao, Zehong Huo, Hong Shi, Jing An, Pengjun Zhang, Ping Zeng, Chi Zhang European Journal of Medical Research.2026;[Epub] CrossRef
Monitoring Sarcopenia With Incretin Receptor Activator Treatment Zachary T. Bloomgarden Journal of Diabetes.2025;[Epub] CrossRef
Correlation Between Serum Creatinine-to-Cystatin C Ratio and Prognosis of Patients with Hip Fracture Wenbin Lu, Miaomiao Rao, Fan Jia, Wubin Chen, Bin Li, Jinjun Bian, Jiafeng Wang International Journal of General Medicine.2025; Volume 18: 4147. CrossRef
Association between creatinine to cystatin C ratio and the incidence of depressive symptoms among middle-aged and older adults: insight from the CHARLS study Xiaohui Li, Guirong Song, Jiaqi Ding, Dongmei Hu, Ying Zhang, Guorong Li, Xiao Tang BMC Psychology.2025;[Epub] CrossRef
Cardiometabolic multimorbidity in relation to the metabolic score for insulin resistance and creatinine-to-cystatin C ratio in a middle-aged and aged population Roushan Zhang, Jian Ma, Li Wang Frontiers in Endocrinology.2025;[Epub] CrossRef
Elevated Serum Triglycerides Independently Predict Incident Falls in Middle‐Aged and Older Adults Kai Deng Geriatrics & Gerontology International.2025; 25(12): 1868. CrossRef