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

Background: Aneurysmal subarachnoid haemorrhage (aSAH) disproportionally affects women. We conducted a systematic review and meta-analysis to explore sex differences in aSAH risk factors. Methods: Case-control/cohort studies were searched to November 2017 with sex-specific risk factors for aSAH. Meta-analysis was performed when a risk factor was reported in ≥2 studies. Results: Of 31 studies, 22 were eligible for meta-analysis. Female sex was associated with greater odds of aSAH (HR_adjusted 1.90 [1.47–2.46]. There was no detectable difference between the sexes for hypertension (OR_adjusted: men 3.13 [2.26–4.34]; women 3.65 [2.87–4.63], p = .18), smoking (OR_adjusted: men 2.96 [1.68–5.21]; women 3.11 [1.21–7.97], p = .95), aSAH family history, systolic blood pressure, age and some genetic variations. Alcohol (OR_adjusted: men 1.50 [1.04–2.17]; women 0.83 [0.48–1.45], p = .003), high alanine aminotransferase levels, and some gene variants increased the risk of aSAH in men. Reproductive factors, divorce and some genetic variations increased the risk in women. High aspartate aminotransferase levels in men and, diabetes (OR_adjusted: men 0.57 [0.32–1.01]; women 0.24 [0.13–0.43], p = .01) and parity in women reduced aSAH risk. Conclusion: We recommend sex-specific re-analysis of existing studies of aSAH risk factors. Known aSAH risk factors (hypertension, smoking and alcohol consumption) should be targeted to prevent aSAH in men and women. Registration PROSPERO (ID: CRD42018091521).