Independent and joint predictive value of Lipid Accumulation Product and estimated Pulse Wave Velocity for incident depressive symptoms: Evidence from CHARLS

BACKGROUND Depression is a major public health concern worldwide, associated with considerable emotional, social, and economic burdens. Emerging evidence suggests that metabolic dysfunction and vascular aging may contribute to the pathogenesis of depression. However, large-scale population studies examining these associations remain limited. OBJECTIVE To investigate the associations of Lipid Accumulation Product (LAP) and estimated Pulse Wave Velocity (ePWV)-markers of metabolic and vascular health-with incident depressive symptoms among Chinese adults. METHODS Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020). A total of 5216 participants aged ≥45 years without depression at baseline were included. LAP and ePWV were calculated using standard formulas. Incident depressive symptoms were assessed using the CES-D-10 (score ≥ 10). Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals across progressively adjusted models. Dose-response relationships were examined using restricted cubic spline models, and subgroup analyses were conducted to assess potential effect modification. Receiver operating characteristic curves were used to evaluate predictive performance. RESULTS During follow-up, 1927 participants developed incident depressive symptoms. Higher levels of both LAP and ePWV were significantly associated with increased depression risk. In fully adjusted models, LAP was positively associated with incident depressive symptoms (HR = 1.04, 95% CI 1.03-1.05), while ePWV showed a stronger association (HR = 1.73, 95% CI 1.66-1.80). Quartile analyses demonstrated significant dose-response relationships (all P for trend <0.001), with the highest quartiles conferring the greatest risk. RCS analyses revealed nonlinear associations for both indicators, with a more pronounced risk increase at higher ePWV levels. Subgroup analyses indicated that the associations were generally consistent across population strata, although the effect of ePWV appeared stronger in certain subgroups such as females and older individuals. ROC analysis showed that ePWV had better predictive performance than LAP (AUC: 0.727 vs. 0.627 in fully adjusted models). CONCLUSIONS Higher LAP and ePWV were associated with incident depressive symptoms among middle-aged and older Chinese adults. ePWV showed better discrimination than LAP; however, the incremental predictive value of adding LAP was limited. These markers may help characterize metabolic and vascular correlates of depressive symptoms but are not sufficient as standalone tools for clinical screening or individual risk prediction.