Abstract

Background: Although the role of radon gas in lung carcinogenesis is well-known, relatively little is known about radon’s role in the pathogenesis or epidemiology of cerebrovascular disease. Methods: We therefore identified postmenopausal women without a history of stroke at the 1993-1998 screening visit of the Women’s Health Initiative Clinical Trials and Observational Study (WHI CT and OS). We linked their geocoded addresses to U.S. Environmental Protection Agency (EPA)-predicted, county-level, indoor, screening radon gas concentrations classified as follows: Zone 3 (<2 pCi/L), Zone 2 (2-4 pCi/L), and Zone 1 (>4 pCi/L). We identified incident strokes based on physician-reviewed, classified, and adjudicated medical records. We measured time from screening to the earliest stroke or censoring date (02/28/20). We used Cox proportional hazards models to estimate radon-related risk of stroke on an attained-age scale as a hazard ratio (HR) and 95% confidence interval (CI), adjusting for WHI design, race/ethnicity, education, homemaker status, U.S. Census region, neighborhood socioeconomic status, smoking, alcohol intake, sodium intake (g/day), 2005 Healthy Eating Index, recreational physical activity (MET-hr/wk), body mass index (kg/m 2 ), systolic blood pressure (mm Hg), as well as history of diabetes, hypercholesterolemia, atrial fibrillation, and deep vein thrombosis/pulmonary embolism. Results: Among 158,906 women (mean, standard deviation [SD] age = 63.1 [7.2] years; 83% white; 9% black; 4% Hispanic; 4% other), we identified 6,979 incident strokes over a mean [SD] follow-up period of 9.3 [5.6] person-years, i.e. 3.41 strokes / 1,000 person-years. The proportion of women with incident stroke was 1.38%, 1.72%, and 1.30% in EPA Radon Zones 3, 2, and 1, respectively. Corresponding incidence rates by EPA Radon Zone were 3.33, 3.43 and 3.49 per 1,000 person-years. Relative to women in Zone 3, those in Zones 2 and 1 had higher adjusted risks of incident stroke: HR (95% CI) = 1.07 (1.00, 1.14) and 1.15 (1.07 , 1.24). Conclusion: Radon gas is a pervasive carcinogen that also may increase susceptibility to a societally burdensome form of cerebrovascular disease, thereby highlighting the potential value of targeted testing, radon-safe construction, and mitigation in stroke prevention.

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