The predictive value of combined assessment of estimated glucose disposal rate and non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio for cardiovascular disease risk: a nationwide cohort study

Background: Insulin resistance and dyslipidemia are important risk factors for cardiovascular disease (CVD). The estimated glucose disposal rate (eGDR) and the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) are effective indicators for assessing insulin sensitivity and the degree of atherosclerosis, respectively. However, the combined effects of different combinations of these two parameters on CVD risk remain unclear. Methods: This study included 6,170 participants with no CVD at baseline, utilizing data from the China Health and Retirement Longitudinal Study (CHARLS). After binary classification of eGDR (median = 10.09) and NHHR (median = 2.81), participants were cross-classified into four groups: high eGDR and low NHHR, high eGDR and high NHHR, low eGDR and low NHHR, and low eGDR and high NHHR. Cox proportional hazards models were used to evaluate the relationship between each group and CVD risk, and the interaction between eGDR and NHHR was further analyzed. Results: During a median follow-up period of 9 years, 1,963 new cardiovascular events in total were recorded. After multivariate adjustment, in contrast to the control group, individuals with low eGDR and high NHHR had the highest CVD risk (HR = 1.78, 95% CI 1.57-2.00), followed by individuals with low eGDR and low NHHR (HR = 1.56, 95% CI 1.36-1.78). In contrast, the combination of high eGDR and high NHHR was not significantly associated with risk (HR = 1.08, 95% CI 0.94-1.25). Cardiovascular disease risk increased significantly with the number of adverse metabolic states (i.e., low eGDR and/or high NHHR). Neither multiplicative nor additive interaction between eGDR and NHHR reached statistical significance. Conclusion: Insulin resistance is an independent and potent risk factor for CVD, even in the absence of significant atherogenic dyslipidemia. Combined assessment of eGDR and NHHR can effectively identify high-risk individuals with a "dual metabolic burden" and those with isolated insulin resistance who are potentially at high risk, providing a simple and practical tool for improving CVD risk stratification and prevention.