Cumulative Joint Burden of Functional Limitation and Depressive Symptoms on Cardiovascular Disease Risk ：A Nationwide Bidirectional Mediation and Competing Risks Analysis

Objectives: To examine independent, joint, and bidirectionally mediated effects of cumulative average functional limitation (FL) and depressive symptoms (DS) on incident cardiovascular disease (CVD) in a nationally representative cohort of Chinese adults aged ≥45 years. Methods: We analyzed 12,274 adults from the China Health and Retirement Longitudinal Study (2011–2018), free of CVD at their wave-specific baseline. Each participant’s baseline was the first survey wave in which they enrolled (waves 1–4). FL was assessed via activities of daily living/instrumental activities of daily living and DS via the 10-item Center for Epidemiologic Studies Depression Scale. Time‐weighted cumulative averages across waves were computed. Fine–Gray competing risks models estimated subdistribution hazard ratios (SHRs) for CVD, accounting for non‐CVD death. Additive and multiplicative interactions and bidirectional mediation were evaluated. Results: Over median 7.0 years of follow-up, 2,294 (18.7%) participants developed CVD. Compared with neither condition, fully adjusted SHRs were 1.63 (95% CI [1.44, 1.85]) for FL only, 1.35 (95% CI [1.17, 1.55]) for DS only, and 2.14 (95% CI [1.92, 2.40]) for both. Additive interaction was significant (RERI = 0.16). Mediation analyses showed DS mediated 23.6% (95% CI [17.7%, 31.0%]) of the FL–CVD association, and FL mediated 28.2% (95% CI [21.2%, 37.0%]) of the DS–CVD association. Discussion: Persistent co‐occurrence of FL and DS markedly increased CVD risk. Reciprocal mediation highlights the need for integrated strategies targeting functional and mental health to disrupt this reinforcing cycle and reduce CVD burden.