The association between short-term nitrogen dioxide (NO2) exposure and ischemic stroke or transient ischemic attacks (TIA): a national study in Israel

Air pollution is an environmental risk factor for stroke, but most studies have focused on fine particulate matter (PM2.5), and fewer have investigated the independent association with exposure to nitrogen dioxide (NO2). We conducted a nationwide case-crossover study including all ischemic stroke or transient ischemic attack (TIA) reported in the Israeli National Stroke Registry from 2014 to 2018. We obtained daily NO2 levels from high-resolution geospatial models and linked them to residential addresses.

We used distributed lag nonlinear models to assess the cumulative association of NO2 exposure over 0–5 lag days, adjusting for PM2.5 and temperature. We further evaluated the modification of the associations by age, sex, urbanicity, and comorbidities (ischemic heart disease, hypertension, and diabetes). We included 85,162 cases, about 54% were males, and the mean age was 71.8.

Cumulative NO2 exposure was associated with increased odds of ischemic stroke or TIA (odds ratio – OR and 95% confidence interval − 1.057 [1.034–1.081]), with the strongest effects 3–5 days before the event. The associations were more pronounced in urban areas (1.064 [1.032;1.097]) compared to suburban areas (1.045 [1.012;1.080]). Although the overall association was similar across ages and sexes, the lag-specific associations on lag days 3–5 were more pronounced in younger adults and women.

Short-term exposure to NO2 is associated with an increased risk of ischemic stroke and TIA, with differential associations across urbanicity, sex, and age groups. These results underscore the urgent need for public health initiatives to reduce NO2 emissions. Particulate matter less than 2.5 microns Multiangle implementation of atmospheric correction International classification of diseases, ninth revision This work was supported by the United States–Israel Binational Science Foundation (BSF), grant number 2021197.

Department of Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA Placidus S. Fernando, Helena Krasnov, Itai Kloog, Mike Z. He & Maayan Yitshak-Sade Neurology Department, Soroka University Medical Center, Beer Sheva, 8410101, Israel Negev Environmental Health Research Institute, Soroka University Medical Center, Beer Sheva, 8410101, Israel Clinical Research Center, Soroka University Medical Center, Beer Sheva, 8410101, Israel Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel The authors declare no competing interests.

This study was approved by the institutional review boards at Soroka University Medical Center in Beer Sheva, Israel (study 01718-19), and the Icahn School of Medicine at Mount Sinai, New York, USA (study 21–00076). A waiver of informed consent was granted due to the minimal risk nature of the study and the use of de-identified registry data with no direct participant contact. All methods were performed in accordance with the relevant institutional and national guidelines and regulations.