Association of depression, physical functioning and incident cardiovascular disease: a national cohort study

Background Converging evidence suggests that impaired physical functioning and depression are closely interconnected, often complicating disease management. Purpose This study aims to provide epidemiological insights into whether depression symptoms and physical functioning interact, mediate, or synergistically contribute to an increased risk of CVD in a nationally representative Chinese population. Methods We included 10,137 middle-aged and older adults without pre-existing CVD from a national, prospective cohort in China. Participants were sampled from 150 counties or districts and 450 rural or urban communities across 28 provinces. Physical functioning was assessed using physical mobility (PM) and activities of daily living (ADL). Impaired PM was defined as having difficulty with any of the following: walking 100 m, climbing stairs, rising from a chair, stooping, arm extension, lifting 5 kg, or picking up a small coin. Impaired ADL was defined as having difficulty with dressing, bathing, eating, bed transfer, toileting, or continence. Depression was assessed using a validated Chinese version of the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10), with depressive symptoms defined as a CESD-10 score of ≥10. Results During a mean follow-up of 7.7 years, 1,922 incident CVD cases occurred. Cross-sectional analysis revealed that impaired ADL and PM were the variables most strongly associated with depression, with odds ratios of 2.19 (95% CI: 1.92–2.48) and 2.68 (95% CI: 2.43–2.96), respectively. Depression was associated with a 19% increased risk of CVD, while impaired ADL and PM increased the CVD risk by 25% and 26%, respectively. Depression status significantly refined the ADL-CVD risk association (P-interaction <0.05) but not the PM-CVD association. Individuals with both depression and impaired physical functioning had a 36% to 38% increased risk of CVD compared to those without. Causal mediation analysis revealed a significant dual mediating role of impaired physical functioning and depression in the development of CVD. Impaired physical functioning mediated a larger proportion of the depression-CVD association (19% to 34%), while depression also significantly mediated the association between impaired physical functioning and CVD (15% to 34%). Conclusions Among Chinese adults, depression and impaired physical functioning exhibit a dual-mediating role and are significantly associated with an increased risk of incident CVD. These findings highlight the importance of integrating physical and mental health assessments into CVD prevention strategies. Interventions targeting both impaired physical functioning and depression could potentially mitigate CVD risk more effectively than addressing either factor alone. Future research should explore the mechanisms underlying these associations and evaluate the effectiveness of integrated intervention programs to inform evidence-based prevention and treatment approaches.