Abstract
BackgroundDepression and insulin resistance-measured by the estimated glucose disposal rate (eGDR)-are both linked to cardiovascular disease (CVD), but whether eGDR mediates this relationship remains unclear. We examined the mediating role of eGDR and its joint and interactive effects with depression on incident CVD.MethodsData were derived from the China Health and Retirement Longitudinal Study (2011-2020). Participants without baseline CVD and with complete eGDR and CESD-10 data were included. eGDR was calculated as 21.158 - (0.09 × waist circumference) - (3.407 × hypertension) - (0.551 × HbA1c). Depressive symptoms were defined as CESD-10 ≥ 12. Cox models adjusted for demographic and lifestyle factors assessed CVD risk across four groups defined by eGDR and depression status.ResultsDuring a median 9-years follow-up, 1643 CVD events occurred. Participants with low eGDR and depression had the highest CVD risk (HR = 1.87, 95% CI: 1.40-2.49, p < 0.001). Additive interaction analysis indicated biological synergy (relative excess risk = 1.37; attributable proportion = 0.32). eGDR mediated 9.82% of the depression-CVD association. Interactions were stronger in older adults.ConclusionLow eGDR and depressive symptoms synergistically elevate CVD risk, highlighting the importance of integrating metabolic and psychological assessments in CVD prevention.