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Review
. 2024 May 9;13(10):2781.
doi: 10.3390/jcm13102781.

Sex-Related Differences in Mortality, Delayed Cerebral Ischemia, and Functional Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

Sarah Berli  1   2 , Massimo Barbagallo  2 , Emanuela Keller  1   2   3 , Giuseppe Esposito  3   4 , Alberto Pagnamenta  5   6   7 , Giovanna Brandi  1   2
Affiliations
Review

Sex-Related Differences in Mortality, Delayed Cerebral Ischemia, and Functional Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

Sarah Berli et al. J Clin Med. .

Abstract

Background/Objective: Sex-related differences among patients with aneurysmal subarachnoid hemorrhage (aSAH) and their potential clinical implications have been insufficiently investigated. To address this knowledge gap, we conduct a comprehensive systematic review and meta-analysis. Methods: Sex-specific differences in patients with aSAH, including mortality, delayed cerebral ischemia (DCI), and functional outcomes were assessed. The functional outcome was dichotomized into favorable or unfavorable based on the modified Rankin Scale (mRS), Glasgow Outcome Scale (GOS), and Glasgow Outcome Scale Extended (GOSE). Results: Overall, 2823 studies were identified in EMBASE, MEDLINE, PubMed, and by manual search on 14 February 2024. After an initial assessment, 74 studies were included in the meta-analysis. In the analysis of mortality, including 18,534 aSAH patients, no statistically significant differences could be detected (risk ratio (RR) 0.99; 95% CI, 0.90-1.09; p = 0.91). In contrast, the risk analysis for DCI, including 23,864 aSAH patients, showed an 11% relative risk reduction in DCI in males versus females (RR, 0.89; 95% CI, 0.81-0.97; p = 0.01). The functional outcome analysis (favorable vs. unfavorable), including 7739 aSAH patients, showed a tendency towards better functional outcomes in men than women; however, this did not reach statistical significance (RR, 1.02; 95% CI, 0.98-1.07; p = 0.34). Conclusions: In conclusion, the available data suggest that sex/gender may play a significant role in the risk of DCI in patients with aSAH, emphasizing the need for sex-specific management strategies.

Keywords: aneurysmal subarachnoid hemorrhage; delayed cerebral ischemia; functional outcome; mortality; sex differences.

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Conflict of interest statement

The authors declare no conflicts of interest. The authors have no competing interests to declare that are relevant to the content of this article.

Figures

Figure 1
Figure 1
Study selection flow diagram according to PRISMA guidelines.
Figure 2
Figure 2
Forest plot of mortality in patients with aSAH analyzed by sex. The risk ratio for mortality at the end of follow-up. Comparison between male and female patients with aneurysmal subarachnoid hemorrhage [12,13,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59]. CI, confidence interval; RR, risk ratio.
Figure 3
Figure 3
Contour-enhanced funnel plot. Mortality studies with contour levels of 0.9, 0.95, and 0.99, respectively.
Figure 4
Figure 4
Forest plot of DCI in patients with aSAH analyzed by sex. The risk ratio for DCI. Comparison between male and female patients with aneurysmal subarachnoid hemorrhage [12,13,14,24,44,45,46,49,54,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104]. CI, confidence interval; DCI, delayed cerebral ischemia; RR, risk ratio.
Figure 5
Figure 5
Contour-enhanced funnel plot. DCI studies with contour levels of 0.9, 0.95, and 0.99, respectively.
Figure 6
Figure 6
Forest plot of the functional outcome in patients with aSAH analyzed by sex, assessed by the mRS, GOS, and GOSE. The risk ratio for functional outcomes. Comparison between male and female patients with aneurysmal subarachnoid hemorrhage [12,13,44,45,46,47,49,57,59,103,105,106,107,108,109,110,111,112]. CI, confidence interval; RR, risk ratio.
Figure 7
Figure 7
Contour-enhanced funnel plot. Functional outcome studies with contour levels of 0.9, 0.95, and 0.99, respectively.
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