Ambient particulate matter air pollution and venous thromboembolism in the women's health initiative hormone therapy trials

Background: The putative effects of postmenopausal hormone therapy on the association between particulate matter (PM) air pollution and venous thromboembolism (VTE) have not been assessed in a randomized trial of hormone therapy, despite its widespread use among postmenopausal women. Objective: In this study, we examined whether hormone therapy modifies the association of PM with VTE risk. Methods: Postmenopausal women 50-79 years of age (n = 26,450) who did not have a history of VTE and who were not taking anticoagulants were enrolled in the Women's Health Initiative Hormone Therapy trials at 40 geographically diverse U.S. clinical centers. The women were randomized to treatment with estrogen versus placebo (E trial) or to estrogen plus progestin versus placebo (E + P trial). We used age-stratified Cox proportional hazard models to examine the association between time to incident, centrally adjudicated VTE, and daily mean PM concentrations spatially interpolated at geocoded addresses of the participants and averaged over 1, 7, 30, and 365 days. Results: During the follow-up period (mean, 7.7 years), 508 participants (2.0%) had VTEs at a rate of 2.6 events per 1,000 person-years. Unadjusted and covariate-adjusted VTE risk was not associated with concentrations of PM < 2.5 μm (PM_2.5) or < 10 μm (PM₁₀)] in aerodynamic diameter and PM × active treatment interactions were not statistically significant (p > 0.05) regardless of PM averaging period, either before or after combining data from both trials [e.g., combined trial-adjusted hazard ratios (95% confidence intervals) per 10 μg/m³ increase in annual mean PM_2.5 and PM₁₀, were 0.93 (0.54-1.60) and 1.05 (0.72-1.53), respectively]. Findings were insensitive to alternative exposure metrics, outcome definitions, time scales, analytic methods, and censoring dates. Conclusions: In contrast to prior research, our findings provide little evidence of an association between short-term or long-term PM exposure and VTE, or clinically important modification by randomized exposure to exogenous estrogens among postmenopausal women.