Sex, Smoking, and Risk for Subarachnoid Hemorrhage

Abstract

Background and Purpose - Women are at higher risk for subarachnoid hemorrhage (SAH) than men for unknown reasons. Also cumulative effects of smoking have been neglected among prospective studies. We studied associations between smoking habits and SAH and interactions between known SAH risk factors in a prospective population-based study. Methods - The population-based FINRISK study cohort of 65 521 individuals was followed up for 1.38 million person-years. We used the Cox proportional hazards model to calculate hazard ratios and evaluated additive and multiplicative interactions between study variables, with all analyses adjusted for known SAH risk factors. Results - During follow-up, we identified 492 SAHs (266 women). Smoking had a linear dose-dependent and cumulative association with risk for SAH in both sexes. Women smoking >20 cigarettes per day had a hazard ratio of 8.35 (95% confidence interval, 3.86-18.06) compared with a hazard ratio of 2.76 (95% confidence interval, 1.68-4.52) in men in the same cigarettes per day group. Hazard ratios differed by sex in all cigarettes per day and pack-year categories; this association was stronger in women in all categories (P=0.01). When an adjusted model included interaction terms between sex and cigarettes per day or pack-years, female sex was no longer an independent SAH risk factor. Former smokers had a markedly decreased risk for SAH in both sexes when compared with current smokers. Conclusions - Smoking has a dose-dependent and cumulative association with SAH risk, and this risk is highest in female heavy smokers. Vulnerability to smoking seems to explain in part the increased SAH risk in women.