Long-term ozone exposure and risk of cerebrovascular and cardiovascular events in patients with atrial fibrillation: a nationwide cohort study
C Wang, B Han, P Jemielita, M Swieczkowski, A Kurasz, S yan, di Zhao, G lip, L KuzmaAbstract
Background
Patients with atrial fibrillation (AF) are at high risk of cerebrovascular and cardiovascular (CV) events. Although short-term effects of air pollution have been described, evidence on the long-term impact of ozone (O₃) exposure in this population remains limited.
Methods
We assembled a population-based cohort of adult residents in Poland (≥18 years; N = 986,206). Among them, 21,073 patients were identified with AF, and after excluding valvular heart disease and dialysis therapy, the final study population comprised 20,757 patients with non-valvular AF(NVAF), who were followed longitudinally for up to 6 years. Exposure to air pollution and meteorological conditions was estimated and assigned according to patients’ residential address. Kaplan–Meier curves were constructed across cumulative average O₃ quartiles to examine event-free survival. Associations were estimated using Fine–Gray competing-risk models with annually time-varying exposure, treating death as a competing event. The primary endpoint was a composite of ischemic stroke (IS), transient ischemic attack (TIA), or stroke-related mortality. CV mortality was the key secondary endpoint. Models were adjusted for demographic characteristics, clinical comorbidities, meteorological factors, area-level socioeconomic status, and co-pollutants.
Results
The final cohort included 20,757 patients with NVAF (mean age 72.6±11.5 years; 52.9% women). Over a follow-up of 6 years, 3,139 composite events and 5,400 CV mortality occurred. Event-free survival declined across increasing O₃ quartiles (log-rank P < 0.001) (Figure 1). In time-varying Fine–Gray models, higher O₃ exposure was associated with increased risks of the composite endpoint, CV mortality, and IS. In the fully adjusted tri-pollutant model, each interquartile range increase in O₃ corresponded to higher risks of the composite endpoint (sHR 1.27, 95% CI 1.02–1.59), CV mortality (sHR 1.14, 95% CI 1.01–1.29), and IS (sHR 1.38, 95% CI 1.08–1.77). Results were consistent across adjustment strategies and sensitivity analyses (Table 2).
Conclusion
Long-term O₃ exposure was linked to higher risks of cardiovascular and cerebrovascular events in patients with atrial fibrillation. The persistence of associations after multi-pollutant adjustment supports a robust relationship. Reducing Long-term ozone exposure may help lower cardiovascular risk in this vulnerable population.O3_NVAF_Primary_CV_Events_Fig1O3_NVAF_FineGray_CompRisk_Table2