Key result
High eGDR and high creatinine-to-cystatin C ratio jointly linked to ~37% lower CVD risk.
Why the study?
Whether the combination of estimated glucose disposal rate and normalized creatinine-to-cystatin C ratio identifies cardiovascular risk beyond either marker alone remains uncertain.
Does the combination of high eGDR and high NCCR reduce incident CVD in middle-aged and older adults free of baseline CVD compared to low eGDR and low NCCR?
Cohort (n=4,935)
Yes
Does the combination of high eGDR and high NCCR reduce incident CVD in middle-aged and older adults free of baseline CVD compared to low eGDR and low NCCR?
Answers are grounded in this paper and cite their sources.
The joint presentation of low eGDR and low NCCR identifies an older adult phenotype at significantly higher risk for incident cardiovascular disease, though NCCR offers limited predictive value improvement when added to a model already containing eGDR.
Background Estimated glucose disposal rate (eGDR) reflects insulin-resistance burden, whereas normalized creatinine-to-cystatin C ratio (NCCR) is a creatinine-cystatin C and body-weight-based biomarker originally proposed as a biochemical correlate of body-weight-adjusted skeletal muscle mass. Whether their combination identifies cardiovascular risk beyond either marker alone remains uncertain. Methods We included 4,935 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study who were free of CVD at baseline in 2011, had eGDR and NCCR values within their respective 1st–99th percentile ranges, and had complete data on Model 3 covariates. Incident CVD was defined as the first self-reported heart disease or stroke through 2020, with event time assigned to the survey year of the first positive report. Cox regression, restricted cubic splines, joint-exposure analyses, prediction evaluation, subgroup analyses, and sensitivity analyses were performed. Multiple imputation was additionally conducted as a sensitivity analysis. Results During a median follow-up of 9 years, 1,235 incident CVD events occurred. Using participants with low eGDR and low NCCR as the reference, those with high eGDR and high NCCR had a fully adjusted HR of 0.629 (95% CI 0.538–0.734). CVD risk decreased progressively across participants with zero, one, and two high markers (P for trend < 0.001). At 9 years, the AUCs were 0.618 for Model 3, 0.638 for Model 3 plus eGDR, 0.623 for Model 3 plus NCCR, and 0.638 for Model 3 plus both markers. Adding NCCR to the model containing eGDR did not produce a discernible improvement in discrimination. Conclusions The combination of low eGDR and low NCCR identified a phenotype with a higher risk of incident CVD, whereas increasing numbers of high markers were associated with progressively lower risk. These findings support the use of eGDR and NCCR for joint epidemiological risk characterization, although the incremental predictive value of NCCR beyond eGDR alone was limited.
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Zhong et al. (2026) conducted a cohort in Incident cardiovascular disease (n=4,935). High estimated glucose disposal rate (eGDR) and high normalized creatinine-to-cystatin C ratio (NCCR) vs. Low eGDR and low NCCR was evaluated on Incident cardiovascular disease (first self-reported heart disease or stroke) (HR 0.629, 95% CI 0.538-0.734, p=<0.001). High estimated glucose disposal rate and high normalized creatinine-to-cystatin C ratio were jointly associated with a 37.1% lower hazard of incident cardiovascular disease (HR 0.629).
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