Association of estimated glucose disposal rate with all-cause and cardiovascular mortality in individuals with cardiovascular-kidney-metabolic syndrome: Two prospective cohorts

• Elevated estimated glucose disposal rate levels were found to be associated with a decreased likelihood of all-cause and cardiovascular mortality among adults with cardiovascular-kidney-metabolic syndrome. • The dose-response curve between estimated glucose disposal rate and all-cause and cardiovascular mortality risks showed a negative linear relationship in individuals with cardiovascular-kidney-metabolic syndrome. • Elevated estimated glucose disposal rate can serve as a promising predictor and therapeutic target for reducing mortality risks among cardiovascular-kidney-metabolic syndrome adults in clinical practice. Given evidence on cardiovascular disease (CVD) risks conferred by comorbidity risk factors, the American Heart Association (AHA) introduced a novel framework, named cardiovascular-kidney-metabolic (CKM) syndrome. Accumulative evidence suggested that the estimated glucose disposal rate (eGDR) was significantly associated with mortality risk. However, it remains unknown whether this association exists in individuals with CKM syndrome. This study aimed to investigate whether eGDR can predict all-cause and cardiovascular mortality risks among adults with CKM syndrome. This study used data from two prospective cohorts: the National Health and Nutrition Examination Survey (NHANES) and the China Health and Retirement Longitudinal Study (CHARLS). The exposure was eGDR at baseline, which was calculated using a combination of waist circumference, hypertension, and hemoglobin A1c. Cox regression models and restricted cubic splines were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders. The main outcomes were all-cause and cardiovascular mortality. A total of 34,809 participants (female: 50.8%, mean age: 46.7 years) and 9,036 from CHARLS (female: 53.3%, mean age: 59.6 years) were included. The median follow-up periods were 8.3 years in NHANES and 9.0 years in CHARLS. Per 1-SD increase in eGDR was associated with 18%-24% lower risks of all-cause mortality after adjusting for confounders (NHANES, HR 0.76, 95% CI 0.71-0.82; CHARLS: HR 0.82, 95% CI 0.77-0.88). In NHANES, the adjusted HR (95% CI) for per 1-SD increase in eGDR was 0.60 (0.53–0.68) for cardiovascular mortality. The dose-response curve between eGDR and mortality risks showed a negative linear relationship in individuals with CKM syndrome. A higher level of eGDR was associated with reduced risk of all-cause and cardiovascular mortality among adults with CKM syndrome. eGDR can serve as a promising predictor and therapeutic target for reducing mortality risks among CKM adults in clinical practice.