Abstract
BACKGROUND: Noise exposure and lower socioeconomic status (SES) are both independently linked to increased cardiovascular disease (CVD) risk. Although these factors frequently coexist, their combined impact and the underlying pathophysiological mechanisms remain poorly understood. OBJECTIVES: This study aimed to evaluate the joint effects of high transportation noise exposure and lower SES on major adverse cardiovascular events (MACE) and the role of the neural-arterial axis in mediating this relationship. METHODS: We retrospectively analyzed data from 507 individuals who underwent clinical (18)F-FDG-PET/CT imaging at a single center. SES was evaluated using local median income (as a primary measure) and area deprivation index (ADI, as a secondary measure). Participants were classified into three groups based on transportation noise exposure and income/ADI: low noise/higher SES, high noise or lower SES, and high noise/lower SES. Cox models assessed MACE risks. Linear regression models evaluated associations with stress-related neural activity (SNA) and arterial inflammation (ArtI). RESULTS: The combination of high noise exposure and low income (vs. neither exposure) associated with increased MACE risk (HR [95% CI]: 5.597 [2.201-14.233], p < 0.001). SNA (standardized β [95% CI]: 0.389 [0.192-0.586], p < 0.001) and ArtI (0.151 [0.005-0.298], p = 0.043) were greater in this group. Mediation analysis showed that the neural-arterial axis contributes to increased exposure-related MACE risk and accounts for 8% of the overall effect. Similar results were found with ADI. IMPACT STATEMENT: Our study uniquely demonstrates how combined high transportation noise and lower socioeconomic status additively increases cardiovascular disease risk through specific biological pathways, particularly via effects on stress-associated neural activity and arterial inflammation. As such, the research offers novel insights into the interplay between environmental and socioeconomic factors in cardiovascular health. This underscores an urgent need for integrated public health strategies that address both noise pollution and socioeconomic disparities and provides a foundation for targeted interventions aimed at reducing the burden of cardiovascular disease in vulnerable populations. Central illustration of hypothesized mechanistic pathways linking transportation noise/SES exposure groups and MACE. SNA stress related neural activity (as AmygAc-ratio of amygdala to background cortical activity), MACE major adverse cardiovascular events, ArtI arterial inflammation, ADI Area Deprivation Index, SES socioeconomic status.