Summer heatwave, ozone pollution and ischemic stroke mortality: An individual-level case-crossover study

Although the association of short-term ozone and heatwave exposure with cerebrovascular disease has been well documented, it remains largely unknown whether their co-exposure could synergistically trigger ischemic stroke (IS) mortality.

We performed an individual-level, time-stratified case-crossover analysis utilizing province-wide IS deaths (n = 59079) in warm seasons (May-September) during 2016-2019, across Jiangsu, eastern China. Heatwave was defined according to a combination of multiple temperature thresholds (90-97.5th percentiles) and durations (2-4 days). Daily estimates of ozone concentration (0.01° × 0.01°) and heatwave (0.1° × 0.1°) were extracted from spatiotemporal grid dataset at subject's residential address. Conditional logistic regression models were utilized to evaluate the associations of short-term ozone and heatwave exposure with IS mortality. Multiplicative and additive interaction effects of ozone and heatwave were assessed using stratified analyses via dividing cases into low and high exposure groups.

Ozone exposure was associated with an increased odds of IS mortality, exhibiting an approximately linear trend across the broad concentration range of 59-227 μg/m³. Under various heatwave definitions, the odds of IS mortality associated with heatwave ranged from 1.167 (95% confidential interval [CI]: 1.135, 1.199) to 1.497 (95% CI: 1.431, 1.565) in the total population. Stratified analyses suggested intensified ozone-related IS risk on heatwave days than non-heatwave days, and intensified heatwave-related risk on high-ozone days than low-ozone days. We observed significant synergistic effects of heatwave and ozone on IS mortality, with relative excess odds due to interaction ranging from 0.15 (95% CI: 0.08, 0.22) to 0.26 (95% CI: 0.13, 0.39). For heatwave with stricter definition, the heatwave and joint ozone-heatwave effects on IS mortality tended to become stronger. We estimated that 3.66% (95% CI: 1.87%, 5.39%) to 4.19% (95% CI: 2.57%, 5.76%) of IS deaths could be attributable to heatwave and ozone exposure. The elderly aged 85+ years were at higher vulnerability to heatwave and co-exposure event of extreme heat and ozone pollution.

Compound ozone and heatwave exposure may synergistically trigger IS deaths, and old adults were at higher vulnerability to exposure-related excess risk. Coordinated governance of climate change and air pollution may potentially bring substantial cerebrovascular health benefit.