Air pollution exposure accelerates the onset and cumulative development of stress related disorders: a pathway to adverse cardiovascular events

Background Air pollution, particularly fine particulate matter (PM2.5), is a known risk factor for major adverse cardiovascular events (MACE) and stress-related disorders (SRDs) such as anxiety, depression, or PTSD. While PM2.5 has been linked to individual SRDs, its role in accelerating the cumulative burden of multiple SRDs over time remains unclear. Moreover, despite the established connection between SRDs and MACE, the potential mediating role of accelerated SRDs development in the PM2.5–MACE relationship remains unexplored. Purpose This study investigates the association between long-term PM2.5 exposure and the progressive accumulation of SRDs, their age of onset, effect modification by social vulnerability, and whether cumulative SRDs development mediates the PM2.5–MACE association. Methods To examine these relationships, we analyzed longitudinal data from the Mass General Brigham Biobank (MGBB). The primary outcome was the 10 year-incidence of any SRDs (i.e, anxiety, depression, or PTSD). Average annual air pollution exposure (PM2.5 [primary], PM10, nitric dioxide [NO2], sulfur dioxide [SO2]) was estimated at the sub-neighborhood level one year before study entry. Neighborhood social vulnerability was assessed using the Social Vulnerability Index (SVI) and stratified into quartiles. MACE, SRDs, and covariables were identified through medical records, ICD-10 codes, and health surveys. Cox proportional hazards and linear regression models were utilized. Mediation analysis quantified the proportion of the PM2.5–MACE association explained by accelerated SRDs accumulation. Results We analyzed 69,663 subjects (814,115 person-years, median [IQR] age: 48 [31–60], 45% male, 15% non-White) from the MGBB (2010–2020). Over a 10-year median follow-up, 15% developed at least one new SRD. In fully adjusted models*, higher PM2.5 exposure associated with an increased risk of SRDs development (HR: 1.090, 95% CI: 1.076–1.105, p<.001; Fig. 1) and an earlier onset by nearly two years (B: -1.703, 95% CI: -1.825 to -1.580, p<.001) per one unit increase in average PM2.5. This effect was most pronounced in individuals with high SVI (SVI-Q4: HR 1.15 vs. Q1: 1.07, p-interaction =0.004; Fig. 2). Mediation analysis showed that accelerated SRD accumulation explained ~17% of the PM2.5–MACE association (Log odds: direct pathway = 0.048, indirect pathway = 0.010, both p<0.05). Similar associations, to varying degrees, were observed with other air pollutants. Conclusion Ambient air pollution drives early onset and cumulative development of SRDs, with the greatest impact observed in socially deprived populations. Moreover, the accumulation of SRDs partially mediates the PM2.5–MACE association, reinforcing the dual threat of environmental pollution to both mental and cardiovascular health. These findings expose critical environmental health disparities and call for urgent, targeted mitigation and public health interventions, particularly in high-risk communities.Figure 1 Figure 2