Sex disparities in case fatality rate after aneurysmal subarachnoid haemorrhage: a prospective longitudinal population-based cohort study

Helena Janssen; Gabriel J E Rinkel; Jos P Kanning; Ynte M Ruigrok; Joanna D Schaafsma

doi:10.1093/esj/aakag094

Sex disparities in case fatality rate after aneurysmal subarachnoid haemorrhage: a prospective longitudinal population-based cohort study

Helena Janssen^*
, Gabriel J E Rinkel
, Jos P Kanning
, Ynte M Ruigrok
, Joanna D Schaafsma

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

INTRODUCTION: While increased female susceptibility to intracranial aneurysm development and rupture is well-known, data on sex differences in case fatality rates (CFR) after aneurysmal subarachnoid haemorrhage (aSAH) remain conflicting. We aimed to investigate sex differences in 90-day CFR post-aSAH and identify explanatory factors.

PATIENTS AND METHODS: The UK Biobank is a prospective population-based cohort study, including 502,411 participants, with baseline assessments between 2006 and 2010. Participants who developed aSAH during follow-up were identified through linkage with hospitalisation records and national death registries. Primary outcome was 90-day CFR post-aSAH. Kaplan-Meier survival analysis and multivariable Cox proportional hazard regression assessed sex disparities in CFR and potential explanatory factors.

RESULTS: We included 990 participants with aSAH, 634 (64.0%) females (age 66.0 ± 8.4) and 356 males (36.0%) (65.1 ± 8.6). At 90 days, 214 of 634 females (33.8%) and 98 of 356 males (27.5%) had died (OR 1.34; 95% CI, 1.01-1.78). Survival analysis demonstrated a sex difference in 90-day CFR (log-rank P = .046) with early divergence and consistently lower survival probability in females. After adjusting for age and covariates that varied by sex at baseline and at time of aSAH, hazard ratio (HR) for case fatality in females was 1.15 (95% CI, 0.90-1.49). In sex-specific multivariable models, HRs for case fatality for age were 1.04 (95% CI, 1.02-1.06) in females and 1.04 (95% CI, 1.01-1.07) in males; for anti-hypertensives use 1.76 (95% CI, 1.23-2.51) and 1.98 (95% CI, 1.23-3.17); and for current smoking 1.87 (95% CI, 1.31-2.67) and 1.64 (95% CI, 0.95-2.82).

DISCUSSION AND CONCLUSION: Females had a higher unadjusted 90-day CFR post-aSAH. This sex difference is partially explained by higher age at aSAH and differences in modifiable baseline risk factors such as hypertension and smoking.

Original language	English
Article number	aakag094
Journal	European Stroke Journal
Volume	11
Issue number	8
DOIs	https://doi.org/10.1093/esj/aakag094
Publication status	Published - Aug 2026

Keywords

Humans
Subarachnoid Hemorrhage/mortality
Female
Male
Prospective Studies
Aged
Middle Aged
Sex Factors
Longitudinal Studies
United Kingdom/epidemiology
Risk Factors
Kaplan-Meier Estimate
Cohort Studies
Intracranial Aneurysm/mortality
Proportional Hazards Models

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@article{c338d2f105434df198307885f456424b,

title = "Sex disparities in case fatality rate after aneurysmal subarachnoid haemorrhage: a prospective longitudinal population-based cohort study",

abstract = "INTRODUCTION: While increased female susceptibility to intracranial aneurysm development and rupture is well-known, data on sex differences in case fatality rates (CFR) after aneurysmal subarachnoid haemorrhage (aSAH) remain conflicting. We aimed to investigate sex differences in 90-day CFR post-aSAH and identify explanatory factors.PATIENTS AND METHODS: The UK Biobank is a prospective population-based cohort study, including 502,411 participants, with baseline assessments between 2006 and 2010. Participants who developed aSAH during follow-up were identified through linkage with hospitalisation records and national death registries. Primary outcome was 90-day CFR post-aSAH. Kaplan-Meier survival analysis and multivariable Cox proportional hazard regression assessed sex disparities in CFR and potential explanatory factors.RESULTS: We included 990 participants with aSAH, 634 (64.0\%) females (age 66.0 ± 8.4) and 356 males (36.0\%) (65.1 ± 8.6). At 90 days, 214 of 634 females (33.8\%) and 98 of 356 males (27.5\%) had died (OR 1.34; 95\% CI, 1.01-1.78). Survival analysis demonstrated a sex difference in 90-day CFR (log-rank P = .046) with early divergence and consistently lower survival probability in females. After adjusting for age and covariates that varied by sex at baseline and at time of aSAH, hazard ratio (HR) for case fatality in females was 1.15 (95\% CI, 0.90-1.49). In sex-specific multivariable models, HRs for case fatality for age were 1.04 (95\% CI, 1.02-1.06) in females and 1.04 (95\% CI, 1.01-1.07) in males; for anti-hypertensives use 1.76 (95\% CI, 1.23-2.51) and 1.98 (95\% CI, 1.23-3.17); and for current smoking 1.87 (95\% CI, 1.31-2.67) and 1.64 (95\% CI, 0.95-2.82).DISCUSSION AND CONCLUSION: Females had a higher unadjusted 90-day CFR post-aSAH. This sex difference is partially explained by higher age at aSAH and differences in modifiable baseline risk factors such as hypertension and smoking.",

keywords = "Humans, Subarachnoid Hemorrhage/mortality, Female, Male, Prospective Studies, Aged, Middle Aged, Sex Factors, Longitudinal Studies, United Kingdom/epidemiology, Risk Factors, Kaplan-Meier Estimate, Cohort Studies, Intracranial Aneurysm/mortality, Proportional Hazards Models",

author = "Helena Janssen and Rinkel, \{Gabriel J E\} and Kanning, \{Jos P\} and Ruigrok, \{Ynte M\} and Schaafsma, \{Joanna D\}",

note = "{\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of the European Stroke Organisation.",

year = "2026",

month = aug,

doi = "10.1093/esj/aakag094",

language = "English",

volume = "11",

journal = "European Stroke Journal",

issn = "2396-9873",

publisher = "SAGE Publications Inc.",

number = "8",

}

TY - JOUR

T1 - Sex disparities in case fatality rate after aneurysmal subarachnoid haemorrhage

T2 - a prospective longitudinal population-based cohort study

AU - Janssen, Helena

AU - Rinkel, Gabriel J E

AU - Kanning, Jos P

AU - Ruigrok, Ynte M

AU - Schaafsma, Joanna D

N1 - © The Author(s) 2026. Published by Oxford University Press on behalf of the European Stroke Organisation.

PY - 2026/8

Y1 - 2026/8

N2 - INTRODUCTION: While increased female susceptibility to intracranial aneurysm development and rupture is well-known, data on sex differences in case fatality rates (CFR) after aneurysmal subarachnoid haemorrhage (aSAH) remain conflicting. We aimed to investigate sex differences in 90-day CFR post-aSAH and identify explanatory factors.PATIENTS AND METHODS: The UK Biobank is a prospective population-based cohort study, including 502,411 participants, with baseline assessments between 2006 and 2010. Participants who developed aSAH during follow-up were identified through linkage with hospitalisation records and national death registries. Primary outcome was 90-day CFR post-aSAH. Kaplan-Meier survival analysis and multivariable Cox proportional hazard regression assessed sex disparities in CFR and potential explanatory factors.RESULTS: We included 990 participants with aSAH, 634 (64.0%) females (age 66.0 ± 8.4) and 356 males (36.0%) (65.1 ± 8.6). At 90 days, 214 of 634 females (33.8%) and 98 of 356 males (27.5%) had died (OR 1.34; 95% CI, 1.01-1.78). Survival analysis demonstrated a sex difference in 90-day CFR (log-rank P = .046) with early divergence and consistently lower survival probability in females. After adjusting for age and covariates that varied by sex at baseline and at time of aSAH, hazard ratio (HR) for case fatality in females was 1.15 (95% CI, 0.90-1.49). In sex-specific multivariable models, HRs for case fatality for age were 1.04 (95% CI, 1.02-1.06) in females and 1.04 (95% CI, 1.01-1.07) in males; for anti-hypertensives use 1.76 (95% CI, 1.23-2.51) and 1.98 (95% CI, 1.23-3.17); and for current smoking 1.87 (95% CI, 1.31-2.67) and 1.64 (95% CI, 0.95-2.82).DISCUSSION AND CONCLUSION: Females had a higher unadjusted 90-day CFR post-aSAH. This sex difference is partially explained by higher age at aSAH and differences in modifiable baseline risk factors such as hypertension and smoking.

AB - INTRODUCTION: While increased female susceptibility to intracranial aneurysm development and rupture is well-known, data on sex differences in case fatality rates (CFR) after aneurysmal subarachnoid haemorrhage (aSAH) remain conflicting. We aimed to investigate sex differences in 90-day CFR post-aSAH and identify explanatory factors.PATIENTS AND METHODS: The UK Biobank is a prospective population-based cohort study, including 502,411 participants, with baseline assessments between 2006 and 2010. Participants who developed aSAH during follow-up were identified through linkage with hospitalisation records and national death registries. Primary outcome was 90-day CFR post-aSAH. Kaplan-Meier survival analysis and multivariable Cox proportional hazard regression assessed sex disparities in CFR and potential explanatory factors.RESULTS: We included 990 participants with aSAH, 634 (64.0%) females (age 66.0 ± 8.4) and 356 males (36.0%) (65.1 ± 8.6). At 90 days, 214 of 634 females (33.8%) and 98 of 356 males (27.5%) had died (OR 1.34; 95% CI, 1.01-1.78). Survival analysis demonstrated a sex difference in 90-day CFR (log-rank P = .046) with early divergence and consistently lower survival probability in females. After adjusting for age and covariates that varied by sex at baseline and at time of aSAH, hazard ratio (HR) for case fatality in females was 1.15 (95% CI, 0.90-1.49). In sex-specific multivariable models, HRs for case fatality for age were 1.04 (95% CI, 1.02-1.06) in females and 1.04 (95% CI, 1.01-1.07) in males; for anti-hypertensives use 1.76 (95% CI, 1.23-2.51) and 1.98 (95% CI, 1.23-3.17); and for current smoking 1.87 (95% CI, 1.31-2.67) and 1.64 (95% CI, 0.95-2.82).DISCUSSION AND CONCLUSION: Females had a higher unadjusted 90-day CFR post-aSAH. This sex difference is partially explained by higher age at aSAH and differences in modifiable baseline risk factors such as hypertension and smoking.

KW - Humans

KW - Subarachnoid Hemorrhage/mortality

KW - Female

KW - Male

KW - Prospective Studies

KW - Aged

KW - Middle Aged

KW - Sex Factors

KW - Longitudinal Studies

KW - United Kingdom/epidemiology

KW - Risk Factors

KW - Kaplan-Meier Estimate

KW - Cohort Studies

KW - Intracranial Aneurysm/mortality

KW - Proportional Hazards Models

U2 - 10.1093/esj/aakag094

DO - 10.1093/esj/aakag094

M3 - Article

C2 - 42593950

SN - 2396-9873

VL - 11

JO - European Stroke Journal

JF - European Stroke Journal

IS - 8

M1 - aakag094

ER -

Sex disparities in case fatality rate after aneurysmal subarachnoid haemorrhage: a prospective longitudinal population-based cohort study

Abstract

Keywords

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