Bidirectional association between gastrointestinal disease and cardiovascular disease: the mediating role of depressive symptoms

Abstract Background Gastrointestinal (GI) disease and cardiovascular disease (CVD) are major contributors to global morbidity and mortality. However, longitudinal population-based evidence regarding their bidirectional relationship and the potential psychological and metabolic-inflammatory mechanisms underlying the gut–heart axis remains limited. Methods We analyzed five waves (2011–2020) of the China Health and Retirement Longitudinal Study (CHARLS), including 13,730 participants without baseline CVD and 12,450 without baseline GI disease. Cox proportional hazards models estimated bidirectional associations, and mediation analyses assessed the contribution of depressive symptoms (CESD-10 scores) and the C-reactive protein–glucose–triglyceride index(CTI). Sensitivity and subgroup analyses were additionally performed. Results Baseline GI disease was associated with incident CVD (HR 1.44, 95% CI 1.32–1.57), and baseline CVD was associated with incident GI disease (HR 1.46, 95% CI 1.30–1.64). Depressive symptoms partially mediated both associations, accounting for 20.6% of the total effect of GI disease on incident CVD and 26.4% of the total effect of CVD on incident GI disease, whereas CTI did not significantly mediate either pathway. The association between baseline CVD and incident GI disease was significant among women (HR 1.51, 95% CI 1.25–1.81) but not men ( P for interaction = 0.01). Findings were robust across sensitivity analyses. Conclusions GI disease and CVD were bidirectionally associated in middle-aged and older Chinese adults. Depressive symptoms may represent a shared psychological pathway underlying the gut–heart axis, whereas CTI did not play a major mediating role. These findings suggest the clinical importance of integrated gastrointestinal, cardiovascular, and psychological health management in aging populations.