Risk factor synergism in aneurysmal subarachnoid hemorrhage: a cross-sectional study.

Background: Spontaneous subarachnoid hemorrhage (SAH) accounts for 5-10% of strokes but a disproportionately large amount of stroke-related morbidity. Several risk factors have been described, including smoking, hypertension, increasing age, and female sex.

Methods: This cross-sectional study examined all patients with aSAH within a nationally representative catchment from 01/01/2017 to 31/12/2020. Patients with aneurysmal SAH were identified from multiple sources, including a prospective database and death records. The population was estimated from projections from a door-to-door census and risk factors from stratified random sampled surveys conducted on a yearly basis. Poisson regression models were used to estimate the incidence and incidence rate ratios (IRRs) for risk factors with 95% confidence intervals (95% CIs).

Results: We identified 875 cases of aSAH in 11,666,807 patient-years of follow-up, which corresponded to a crude incidence of 7.5 per 100,000 patient-years (95% CI 7-8) and a standardized incidence of 6.1/100,000 (95% CI 5.6-6.5). Smoking was the strongest individual risk factor, with a standardized incidence of 24/100,000 (95% CI 20-27) in smokers compared with 2.6/100,000 (2.1-3.2) in non-smokers (age-adjusted IRR 9.2, 95% CI 6.3-13.6). Hypertension (age-adjusted IRR 3.1, 95% CI 2.2-4.3) and female sex (age-adjusted IRR 1.8, 95% CI 1.4-2.3) were also associated with increased incidence. The highest incidence was observed in hypertensive smokers (standardized incidence 63/100,000, 95% CI 41-84), who had a lifetime risk of aSAH of 6.7% (95% CI 5.4-8.1) after age 35. Compared with participants who were non-smokers without hypertension, the age-adjusted IRR in hypertensive smokers was 27.9 (95% CI 15.9-48.8).

Conclusion: Smoking is the most prominent individual risk factor for aSAH. Smoking and hypertension appear to interact to increase the risk of aSAH synergistically.