Additive effects of anxiety/depression and transportation noise exposure on cardiovascular risk and measures of neural-immune mechanisms.

BACKGROUND: Transportation noise exposure and stress-related psychiatric conditions (e.g., anxiety, depression) are well-known contributors to cardiovascular disease (CVD). Both exposures activate shared biological pathways, including heightened stress-associated neural activity (SNA), autonomic dysfunction, and systemic inflammation that culminate in CVD; however, it remains unknown whether their co-occurrence confers additive CVD risk. OBJECTIVE: We hypothesized that individuals with both anxiety and/or depression and high noise exposure (vs. those with one or neither exposure) have greater CVD risk through a heightened impact on neural-immune intermediaries, and that measures of these intermediaries mediate the association between these combined exposures and major adverse cardiovascular event (MACE) risk. METHODS: We retrospectively evaluated individuals (N = 25,906) from the Mass General Brigham Biobank. Diagnoses of anxiety and/or depression, MACE, and covariables were determined with International Classification of Disease codes and surveys. Transportation noise was assessed as the annual 24-hour average at each individual's home address using a US government tool. Values >45 dBA were deemed elevated. Measures of neural-immune intermediaries (i.e., SNA, heart rate variability (HRV, a measure of autonomic dysfunction as standard deviation of normal-to-normal intervals), and C-reactive protein, (CRP, a measure of systemic inflammation)) were assessed from clinically available data. Individuals were grouped by number of exposures to depression and/or anxiety and high noise (as 0, 1, or 2) for analyses. Cox models, linear and logistic regression, and mediation analyses were implemented. RESULTS: Anxiety and/or depression and high noise exposure had an additive association with MACE (adjusted HR [95% CI]: 1.17 [1.07, 1.28], p < 0.001) that was independent of CVD risk factors and other socioenvironmental confounders. The number of exposures associated with stepwise increases in SNA (adjusted standardized β: 0.059, p = 0.046) and reductions in HRV (-0.078, p < 0.001), and there was a non-significant relationship with CRP (0.030, p = 0.06). There was no significant interaction. Additionally, lower HRV significantly mediated the exposure-MACE link. CONCLUSIONS: Individuals with anxiety and/or depression may be more vulnerable to transportation noise due to additive associations with CVD event risk and measures of stress-related neural-immune intermediaries. Accordingly, individuals with both anxiety and/or depression and high noise exposure may benefit from targeted interventions integrating environmental and psychosocial approaches.