Associations of PM2.5 Components, Residential Greenness, and Heatwaves with Incident Venous Thromboembolism

AIMS: This study aimed to explore the associations of fine particulate matter (PM2.5) components, residential greenness, and heatwaves with incident venous thromboembolism (VTE). METHODS: This study included 483,610 participants from the UK Biobank (mean age 56.5 years; 54.3% female). Exposures included PM2.5 components (elemental carbon, organic matter, sulfate, ammonium, and nitrate) estimated at a 3×3 km resolution, residential greenness measured by Normalised Difference Vegetation Index within 300 m buffers, and heatwaves defined using multiple temperature thresholds. The outcome was identified through hospital admission and death records. Cox proportional hazards models along with interaction and mediation analyses were fitted. RESULTS: During a median follow-up of 11.83 years, 9,988 incident VTE cases were identified. Each interquartile range increase in exposure to elemental carbon, sulfate, and ammonium was positively associated with VTE risk, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.052 (1.005, 1.101), 1.064 (1.001, 1.130), and 1.090 (1.010, 1.176), respectively. Elemental carbon showed the strongest association among these components. Each interquartile range increase in residential greenness was associated with lower VTE risk (HR: 0.944, 95% CI: 0.916, 0.972), with specific PM2.5 components (elemental carbon and ammonium) partly mediating this association. Under different heatwave definitions, the HRs (95% CIs) for incident VTE ranged from 1.149 (1.137, 1.161) to 1.407 (1.396, 1.417). Significant additive interactions with heatwaves under different definitions were identified for sulfate and ammonium, but not consistently for other PM2.5 components or residential greenness, on VTE risk. Genetic factors, assessed by a polygenic risk score, showed significant additive interactions with ammonium and nitrate, as well as a multiplicative interaction with residential greenness, suggesting that genetic susceptibility may modify these associations. CONCLUSIONS: This study identified that exposure to specific PM2.5 components, low residential greenness, and heatwaves were associated with elevated VTE risk.