Sex differences in risk factors for aneurysmal subarachnoid hemorrhage: Systematic review and meta-analysis.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) disproportionally affects women. The etiology of this is unclear, and the contribution of sex differences in aSAH risk factors is unknown. We aimed to identify sex differences in aSAH risk factors in a systematic review and meta-analysis. Method(s): A systematic search was conducted using the Pubmed, Scopus, Embase, and Medline databases from inception to November 2017 to identify studies that included aSAH risk factors stratified by sex. aSAH risk factors were assessed using meta-analysis with pooled odds ratios (OR) calculated for risk factors with at least 2 studies. Result(s): There were 34 eligible case-control studies; however, 15 did not report sex specific findings with 19 were included. Hypertension (men pooled ORadjusted 3.13 [95% CI 2.26-4.34]; women pooled ORadjusted 3.65 [95% CI 2.87-4.63], p=0.18), smoking (men pooled ORadjusted 2.96 [95% CI 1.68-5.21]; women pooled ORadjusted 3.11 [95% CI 1.21-7.97], p=0.95),family history of aSAH, increased systolic blood pressure, age, angiotensin-converting enzyme gene polymorphism and variation in a protease gene had the same odds for aSAH in both sexes. Alcohol intake (men pooled ORadjusted 1.50 [95% CI 1.04-2.17], women pooled ORadjusted 0.83 [95% CI 0.48-1.45], p=0.003), high alanine aminotransferase levels, and endothelial nitric oxide synthase gene variant were associated with higher odds of aSAH in men than women. Cold temperature, polymorphisms in factor XIII gene and genetic variation on chromosome 9p21 increased the odds of aSAH in women but not men. High aspartate aminotransferase levels were associated with a reduced risk in men while diabetes mellitus decreased the risk in women (men pooled ORadjusted 0.57 [95% CI 0.32- 1.01], women pooled ORadjusted 0.24 [95% CI 0.13-0.43], p=0.017). Conclusion(s): Except for alcohol intake and diabetes mellitus, the magnitude of aSAH risk associated with most common risk factors were similar for both sexes. We adv