Abstract 4360783: Accentuated Effect of Transportation Noise Exposure on Cardiovascular Risk in Individuals with Anxiety and Depression

Background: Stress-related psychiatric conditions (e.g., anxiety, depression) independently increase cardiovascular disease (CVD) risk. This association is mediated by neural-immune mechanisms, including stress-related neural activity (SNA), altered autonomic activity, and heightened systemic inflammation. Chronic exposure to transportation noise also associates with an increased risk of major adverse cardiovascular events (MACE) through similar mechanisms. Objectives: We evaluated whether anxiety and/or depression and higher transportation noise exposure (>45 dBA) have an additive impact on 1) MACE risk, 2) key neural-immune intermediaries, and 3) whether these intermediaries mediate the link between noise exposure and MACE. Methods: Individuals with transportation noise exposure and anxiety/depression data were identified in the Mass General Brigham Biobank. Average 24-h transportation noise was estimated at everyone’s home address using a US Department of Transportation tool. Presence and timing of anxiety/depression, MACE, and key confounders were determined using ICD-10 codes and US government data. SNA, autonomic activity (as heart rate variability, HRV), and systemic inflammation (as C-reactive protein, CRP) were evaluated in individuals with available clinical data. Cox regression and mediation analyses were employed. Results: Among 18,868 individuals (median age 63 years; 51.1% females), anxiety and/or depression and noise exposure >45 dBA had an additive effect on MACE risk (HR: 1.283, p<0.001, Figure 1A) that persisted with adjustment for age, sex, and CVD risk factors (i.e., smoking, diabetes, hypertension, hyperlipidemia). This association persisted after adjustment for age, sex, median neighbourhood income, and air pollution (1.187, p = 0.002). There was also an additive effect of both exposures on SNA (standardized ß: 0.060, p=0.024, Figure 1B), HRV (-0.086, p<0.001, Figure 1C), and CRP (0.031, p=0.029, Figure 1D) in models adjusted for age and sex. Further, HRV mediated the relationship between anxiety/depression and MACE among individuals with high (but not low) noise exposure (indirect pathway log odds: 0.076, p<0.05). Conclusions: Anxiety and/or depression and high transportation noise exposure have an additive adverse effect on MACE risk and key neural-immune intermediaries. These findings provide mechanistic insights into how those with anxiety and/or depression may have greater susceptibility to CVD consequent to noise exposure.