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Background <p>The normalized creatinine-to-cystatin C ratio (NCCR) has been identified as a viable metric for assessing skeletal muscle mass and diabetes risk. However, the relationship between NCCR and cardiovascular disease (CVD) remains insufficiently understood. This study aims to clarify this association within a national, longitudinal, and prospective cohort.</p> Methods <p>Participants were selected from the China Health and Retirement Longitudinal Study to form the study cohort. Baseline NCCR was designated as the exposure variable, while the primary outcome was the incidence of newly diagnosed CVD. Participants were divided into four groups (Q1–Q4) based on the quartiles of baseline NCCR. The risk of CVD across different NCCR groups was assessed using Cox proportional hazards models and Kaplan–Meier survival curves. Restricted cubic spline (RCS) analysis was conducted to investigate the nature of the association between NCCR and CVD. Additionally, the receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of NCCR for CVD.</p> Results <p>A total of 5,486 individuals participated in the study, with a median age of 59&#xa0;years, of whom 2987 (52.42%) were male. During an average follow-up period of 7.62&#xa0;years, 1440 participants (25.27%) were diagnosed with CVD. According to fully adjusted Cox proportional hazards models, participants in the Q2, Q3, and Q4 groups exhibited a significantly reduced risk of developing CVD compared to those in the Q1 group, with hazard ratios (HR) and 95% confidence intervals (CI) of 0.81 (0.70–0.93), 0.80 (0.69–0.93), and 0.73 (0.63–0.85), respectively. Restricted cubic spline (RCS) analysis demonstrated a linear association between NCCR and the incidence of CVD (P overall &lt; 0.001, P for nonlinearity = 0.079). The receiver operating characteristic (ROC) curve for NCCR in predicting CVD showed an area under the curve (AUC) of 0.556.</p> Conclusion <p>The baseline NCCR exhibits an inverse correlation with the risk of CVD in individuals diagnosed with cardiovascular–kidney–metabolic (CKM) syndrome at stages 0 to 3. Consequently, it may serve as a valuable biomarker for assessing CVD risk in this population.</p> Graphical Abstract <p></p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月21日

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  • Defei Chen,
  • Yuhui Li,
  • Tailin Ran,
  • Fu Song,
  • Zheng Yang,
  • Weilin Tan,
  • Qiuyi Lu,
  • Lanxin Tang,
  • Lining Yang,
  • Dingqun Bai

摘要

Background

The normalized creatinine-to-cystatin C ratio (NCCR) has been identified as a viable metric for assessing skeletal muscle mass and diabetes risk. However, the relationship between NCCR and cardiovascular disease (CVD) remains insufficiently understood. This study aims to clarify this association within a national, longitudinal, and prospective cohort.

Methods

Participants were selected from the China Health and Retirement Longitudinal Study to form the study cohort. Baseline NCCR was designated as the exposure variable, while the primary outcome was the incidence of newly diagnosed CVD. Participants were divided into four groups (Q1–Q4) based on the quartiles of baseline NCCR. The risk of CVD across different NCCR groups was assessed using Cox proportional hazards models and Kaplan–Meier survival curves. Restricted cubic spline (RCS) analysis was conducted to investigate the nature of the association between NCCR and CVD. Additionally, the receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of NCCR for CVD.

Results

A total of 5,486 individuals participated in the study, with a median age of 59 years, of whom 2987 (52.42%) were male. During an average follow-up period of 7.62 years, 1440 participants (25.27%) were diagnosed with CVD. According to fully adjusted Cox proportional hazards models, participants in the Q2, Q3, and Q4 groups exhibited a significantly reduced risk of developing CVD compared to those in the Q1 group, with hazard ratios (HR) and 95% confidence intervals (CI) of 0.81 (0.70–0.93), 0.80 (0.69–0.93), and 0.73 (0.63–0.85), respectively. Restricted cubic spline (RCS) analysis demonstrated a linear association between NCCR and the incidence of CVD (P overall < 0.001, P for nonlinearity = 0.079). The receiver operating characteristic (ROC) curve for NCCR in predicting CVD showed an area under the curve (AUC) of 0.556.

Conclusion

The baseline NCCR exhibits an inverse correlation with the risk of CVD in individuals diagnosed with cardiovascular–kidney–metabolic (CKM) syndrome at stages 0 to 3. Consequently, it may serve as a valuable biomarker for assessing CVD risk in this population.

Graphical Abstract