Differential impacts of long-term exposure to ozone pollution on mortality in patients with hemorrhagic versus ischemic stroke: a retrospective cohort study

Evidence suggests that increased ozone (O3) pollution is linked to increased incidence and mortality of cardiovascular disease in general populations. However, the relationship between long-term exposure to ambient O3 and mortality in stroke patients remains inconclusive. The objective of this study was to investigate the impacts of long-term O3 exposure on all-cause and cause-specific mortality following first-incident hemorrhagic or ischemic stroke. We conducted a retrospective study (from 2013 to 2019) in patients with first-incident stroke. The participants (40 to 99 years of age) were collected from 20 counties in Shandong Province, China. The annual and warm-season average concentrations of O3 were derived from the daily maximum 8-hour average O3 data obtained from a published dataset. The associations were determined using Cox-equivalent re-parameterized Poisson model. The current study analyzed 330,486 participants (mean age 68.3 ± 11.6; 46.4% females), including 53,314 hemorrhagic and 277,172 ischemic stroke cases. In hemorrhagic stroke patients, both annual and warm-season O3 were positively associated with all-cause and stroke-specific mortality, independent of PM2.5 (particles less than 2.5 μm) and NO2 (hazard ratios ranging from 1.236 to 1.309, all P < 0.05). Exposure-response analysis indicated a threshold of O3 concentration (around 120–140 µg/m3) for its deleterious effects. The impacts of O3 on stroke-specific and all-cause mortality were confirmed in subgroup (sex, age, residential areas) and sensitivity (using time-dependent Cox regression and 1-year-lag models) analyses. In contrast, the associations between O3 and mortality risk in ischemic stroke patients were weak and unstable, which should be interpreted with caution. Long-term exposure to O3 pollution is associated with increased mortality in hemorrhagic stroke patients. It appears that O3 has differential impacts on hemorrhagic and ischemic stroke mortality, although more robust data are needed for ischemic stroke. Future prospective studies are warranted with hemorrhagic and ischemic stroke being analyzed separately.