Chronic exposure to air pollutants may significantly increase the risk of venous thromboembolism, with risk ratios even higher among non-smokers and during the first decade of exposure, according to a new analysis of the Multi-Ethnic Study of Atherosclerosis.
The prospective cohort study, published in Blood, found that among nonsmokers specifically (n = 5,786), PM2.5 exposure was associated with a 42% increased venous thromboembolism (VTE) risk (hazard ratio [HR] = 1.42, 95% confidence interval [CI] = 1.05–1.92), while NO2 exposure more than doubled the risk (HR = 2.55, 95% CI = 1.47–4.45).
When investigators restricted analysis to the first 10 years of follow-up, the associations strengthened considerably:
- PM2.5: HR = 1.94 (95% CI = 1.35–2.79)
- NO2: HR = 3.38 (95% CI = 1.66–6.86)
- NOx: HR = 2.25 (95% CI = 1.32–3.84).
"The magnitudes of association tended to be stronger with shorter follow-up," noted the study authors.
The investigators analyzed baseline inflammatory and coagulation markers, finding that participants with higher PM2.5 exposure showed elevated levels of fibrinogen (mean = 353.2 mg/dL in highest quartile vs 344.1 mg/dL in lowest quartile) and factor VIII (102% vs 96%).
Important clinical characteristics of the cohort included:
- Mean body mass index: 28.3 ± 5.5 kg/m2
- Never smokers: 50.4%
- Former smokers: 36.6%
- Current smokers: 13.0%
- Median D-dimer: 0.2 [0.1, 0.4] µg/mL
- Mean fibrinogen: 346.6 ± 73.9 mg/dL
- Median interleukin-6: 1.2 [0.8–1.9] pg/mL
- Median CRP: 1.9 [0.8–4.2] mg/L.
Among the 248 VTE events documented, 156 were non–cancer related. When analyzing only non-cancer VTE cases, the associations strengthened for PM2.5 (HR = 1.59, 95% CI = 1.15–2.18) and NO2 (HR = 3.14, 95% CI = 1.65–5.95).
The investigators identified VTE events using hospital discharge codes, including both deep vein thrombosis and pulmonary embolism. The study methodology excluded participants using anticoagulants at baseline (n = 39) and those with missing air pollution exposure data during follow-up (n = 71).
In sensitivity analyses, results remained robust after excluding current smokers, adjusting for neighborhood socioeconomic status, and accounting for baseline respiratory disease. However, there was no evidence of association among the 11% of participants with respiratory disease at baseline, though precision was poor for this subgroup analysis.
The study's sophisticated air pollution measurement methodology incorporated community-specific monitoring with measurements from 27 long-term sites, 771 community snapshot locations, and outside 697 participants' homes between 2005 and 2009.
Study limitations included the inability to capture outpatient VTE events and lack of medical record validation for hospital discharge codes. Additionally, while inflammatory and coagulation mediators were measured at baseline, the lack of repeated measurements throughout follow-up limited the ability to evaluate their role in mediating the pollution-VTE relationship.