Air pollution exposure accelerates the onset and cumulative development of cardiovascular risk factors: mediating pathway to adverse cardiovascular events

Abstract Background Air pollution, particularly fine particulate matter with aerodynamic diameter 2.5 (PM2.5), is linked to individual cardiovascular risk factors (CVDRFs) such as hypertension (HTN), hyperlipidemia (HLD), and diabetes (DM). However, its role in accelerating the cumulative development of multiple risk factors and mediating major adverse cardiovascular events (MACE) remains unclear. Purpose This study examines the association between long-term PM2.5 exposure and progressive CVDRFs accumulation, the timing of their onset, the effect modification by social vulnerability, and whether accelerated CVDRFs development mediates the PM2.5 – MACE relationship. Methods To assess these associations, we analyzed longitudinal data from the Mass General Brigham Biobank (MGBB). The primary outcome was the onset of new CVDRFs (HTN, HLD, DM). Average annual air pollution exposure (PM2.5 primary, PM10, Nitric dioxide NO2, Sulfur dioxide SO2) was estimated at the sub-neighborhood level that included each individual’s home address, one year before study index date. Neighborhood social deprivation was assessed using the Social Vulnerability Index (SVI) and stratified into quartiles. MACE, CVDRFs, and covariables were identified through medical records, ICD-10 codes, and health surveys. Cox proportional hazards and linear regression models were employed. Mediation analysis quantified the proportion of the PM2.5 – MACE association explained by accelerated CVDRF accumulation. Results We analyzed 83,384 subjects (942,200 person-years, median IQR age: 49 33–61 years, 43% male, 16% non-White) from the MGBB (2010–2020). Over a 10-year median follow-up, 40% developed at least one new CVDRF. In fully adjusted models*, higher PM2.5 exposure associated with an increased risk of new CVDRF development (HR: 1.054, 95% CI: 1.043–1.065, p0.001; Fig. 1) and an earlier onset by nearly two years (β: -1.729, 95% CI: -1.869 to -1.589, p.001) per one unit increase in average PM2.5. This effect was most pronounced in individuals with high SVI (SVI-Q4: HR 1.08 vs. Q1: 1.01, p-interaction 0.001; Fig. 2). Mediation analysis showed that accelerated CVDRF accumulation explained ~33% of the PM2.5–MACE association (Log odds: direct pathway = 0.004, indirect pathway = 0.002, p0.05). Similar associations, to varying degrees, were observed with other air pollutants. Conclusion Long-term air pollution exposure accelerates the onset and cumulative development of CVDRFs. This effect is amplified in socially vulnerable populations, and accelerated risk factor accumulation partially mediates the PM2.5 – MACE association. These findings highlight environmental health disparities and urgently call for pollution mitigation and public health interventions, particularly for high-risk groups.Figure 1 Figure 2