U-shaped relationship of estimated glucose disposal rate with cardiovascular disease risk in cardiovascular-kidney-metabolic syndrome stages 0–3: a population-based prospective study

BACKGROUND: Cardiovascular-Kidney-Metabolic (CKM) syndrome is characterized by the interrelatedness of chronic kidney disease (CKD), cardiovascular disease (CVD), and metabolic disorders. The relationship between estimated glucose disposal rate (eGDR) and CVD risk in CKM syndrome remains unclear. METHODS: We analyzed data from 7,849 participants aged ≥ 45 years in the China Health and Retirement Longitudinal Study (CHARLS). The eGDR was calculated using waist circumference, hypertension, and HbA1c. Cox regression and restricted cubic spline (RCS) regression analyses examined the association between eGDR and CVD (stroke or cardiac events). RESULTS: During a mean follow-up of 8.29 ± 1.67 years, among 7,849 participants (mean age 62.4 ± 8.7 years; 52.82% male), 1,946 CVD events occurred, including 1,504 cardiac events and 663 strokes. CKM stages 0-3 comprised 492 (6.27%), 1,404 (17.89%), 5,462 (69.59%), and 491 (6.26%) of participants, respectively. A U-shaped relationship between eGDR and CVD risk was identified (turning point: 11.82 mg/kg/min). Below this turning point, each unit increase in eGDR decreased CVD risk by 12% (HR: 0.88, 95% CI: 0.86-0.90, P < 0.0001); above it, each unit increase raised the risk by 19% (HR: 1.19, 95% CI: 1.04-1.37, P = 0.0135). CONCLUSION: Our findings reveal a U-shaped relationship between eGDR and CVD risk in CKM syndrome stages 0-3. A higher or lower eGDR was associated with an increased CVD risk.