Prognostic effect of estimated glucose disposal rate on all-cause and cardiovascular mortality among individuals cardiovascular-kidney-metabolic syndrome

Abstract Background The American Heart Association (AHA) recently proposed the cardiovascular-kidney-metabolic (CKM) syndrome, which is a complicated interaction between chronic kidney disease (CKD), cardiovascular disease (CVD), and metabolic dysfunction that might have negative consequences. One of the main causes of CKM is insulin resistance (IR), and one useful indicator of IR is the estimated glucose disposal rate (eGDR). Methods 14,472 patients with CKM stages 1–4 from the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2016 were included in this study. The NHANES public use mortality files provided the mortality data. The eGDR was calculated using the validated formula: eGDR = 21.158 − (0.09 * WC) − (3.407 * HT) − (0.551 * HbA1c) WC = waist circumference (cm), HT = hypertension (yes = 1/no = 0), and HbA1c = HbA1c (%). The association between eGDR and mortality in patients with CKM syndrome stages 1–4 was examined using Kaplan–Meier(K-M) curves, Cox regression analysis, restricted cubic spline (RCS) regression analysis, and subgroup analysis. Results During follow-up period of 8.83 years, 2,118 all-cause mortality events were recorded. Among individuals with CKM syndrome stages 1–4, Cox analysis indicated that a higher eGDR was associated with a lower incidence of all-cause mortality (Q2: HR 0.84, 95% CI 0.75–0.94; Q3: HR 0.83, 95% CI 0.73–0.93; Q4: HR 0.71, 95% CI 0.60–0.83, all p < 0.05), the same trend was observed in cardiovascular mortality. Additionally, the RCS curve confirmed the association of eGDR with both all-cause and CVD mortality remained linear across CKM patient populations. Subgroup analysis revealed significant effect modification: the association between eGDR and both all-cause and CVD mortality outcomes was markedly stronger in participants aged < 65 years, with males showing a particularly enhanced association for all-cause mortality (p for interaction < 0.001). Conclusions This study identified that low eGDR levels in patients with CKM syndrome stages 1–4 were associated with increased all-cause and cardiovascular mortality risk, with the association markedly stronger among participants aged < 65 years. These findings reinforce eGDR as a valuable risk index, particularly as a more sensitive early-warning marker in younger populations before traditional metabolic markers become overtly pathological.