Sex Differences in Case Fatality of Aneurysmal Subarachnoid Hemorrhage: A Systematic Review

Abstract

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) is more common in women than in men, contrary to most cardiovascular diseases. However, it is unclear whether the case fatality rate (CFR) of SAH also differs by sex. Thus, we performed a systematic review to address the relationship between sex and SAH CFRs.

Methods: We conducted a systematic literature search in PubMed, Scopus, and Cochrane library databases. We focused on population-based studies that included both nonhospitalized and hospitalized SAHs and had either reported 1-month (28-31 day) SAH CFRs separately for men and women or calculated risk estimates for SAH CFR by sex. For quality classification, we used the Cochrane Collaboration Handbook and Critical Appraisal Skills Program guidelines. We pooled the study cohorts and calculated relative risk ratios (RRs) with 95% confidence intervals (CIs) for SAH death between women and men using a random-effects meta-analysis model.

Results: The literature search yielded 5,592 initial publications, of which 33 study cohorts were included in the final review. Of the 33 study cohorts, only three reported significant sex differences, although the findings were contradictory. In the pooled analysis of all 53,141 SAH cases (60.3% women) from 26 countries, the 1-month CFR did not differ (RR = 0.99 [95% CI: 0.93-1.05]) between women (35.5%) and men (35.0%). According to our risk-of-bias evaluation, all 33 study cohorts were categorized as low quality. The most important sources of bias risks were related to the absence of proper confounding control (all 33 study cohorts), insufficient sample size (27 of 33 study cohorts), and poor/unclear diagnostic accuracy (27 of 33 study cohorts).

Conclusion: Contrary to SAH incidence rates, the SAH CFRs do not seem to differ between men and women. However, since none of the studies were specifically designed to examine the sex differences in SAH CFRs, future studies on the topic are warranted.

Keywords: Case fatality; Epidemiology; Sex differences; Subarachnoid hemorrhage; Systematic review.

Fig. 1.

Flowchart of the literature review.

Fig. 2.

Risk-of-bias classification by domain.

Fig. 3.

Pooled subarachnoid hemorrhage (SAH) case fatality rates (CFRs) and risk ratios (RRs) for death in women versus men (reference group) with 95% CIs by study region. Pooled risk ratios were calculated with a random-effects meta-analysis model. For the forest plot, see online supplementary Figure 1. Europe was further divided into subregions according to the Publications Office of the European Union (https://op.europa.eu/en/home. Accessed May 10, 2023) due to the large number of studies and differences in population structures. Continents, countries, and covered regions: (1) Northern Europe (Finland [Nationwide, Kuopio, North Karelia, and Turku/Loimaa], Sweden [Nationwide, Umeå, Göteborg, and Malmö], Norway [Nord-Trøndelag and Tromsø], Denmark [Glostrup], Lithuania [Kaunas]). (2) Western Europe (The UK [Nationwide and Devon/Cornwall], France [Dijon]). (3) Southern Europe (Italy [L’Aquila and Friuli], Greece [Evros]). (4) Central and Eastern Europe (Poland [Warsaw], Serbia [Novi Sad], and Russia [Moscow]). (5) North America (The US [Northern Manhattan, Greater Cincinnati/Northern Kentucky, and Framingham], French West [Martinique]). (6) South America (Chile [Aconcagua Valley and Ñuble]). (7) Asia (China [Middle/Eastern China and Beijing], Japan [Okinawa, Akita, and Shiga]). (8) Oceania (New Zealand [Auckland]). (9) Multinational (Argentina [Tandil], Brazil [Joinville and Matão], French West [Martinique], Sweden [Orebro], Estonia [Tartu], Portugal [Porto], Italy [L’Aquila], New Zealand [Auckland], Australia [Melbourne], India [Ludhiana], Iran [Mashhad], no individual CFRs for countries). * Ingall et al. [33] removed due to lack of sex-specific numbers of fatal and total SAHs. ^† Sandvei et al. [41] removed due to lack of sex-specific number of fatal SAHs.

Fig. 4.

Funnel plot of risk ratio for 1-month SAH case fatality in women versus men (reference group).