Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis
Zuurbier, Charlotte C.M.; Molenberg, Rob; Mensing, Liselore A.; Wermer, Marieke J.H.; Juvela, Seppo; Lindgren, Antti E.; Jääskeläinen, Juha E.; Koivisto, Timo; Yamazaki, Tomosato; Uyttenboogaart, Maarten; van Dijk, J. Marc C.; Aalbers, Marlien W.; Morita, Akio; Tominari, Shinjiro; Arai, Hajime; Nozaki, Kazuhiko; Murayama, Yuichi; Ishibashi, Toshihiro; Takao, Hiroyuki; Gondar, Renato; Bijlenga, Philippe; Rinkel, Gabriel J.E.; Greving, Jacoba P.; Ruigrok, Ynte M.
(2022) Stroke, volume 53, issue 2, pp. 362 - 369
(Article)
Abstract
BACKGROUND AND PURPOSE: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by
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insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. METHODS: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. RESULTS: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). CONCLUSIONS: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.
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Keywords: Age Factors, Aged, Aneurysm, Ruptured/epidemiology, Cohort Studies, Female, Humans, Intracranial Aneurysm/complications, Male, Middle Aged, Prevalence, Prospective Studies, Risk Factors, Sex Factors, Smoking/epidemiology, Subarachnoid Hemorrhage/complications, Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't
ISSN: 0039-2499
Publisher: Lippincott Williams & Wilkins
Note: Funding Information: We acknowledge the support from the Netherlands Cardiovascular Research Initiative: An initiative with support of the Dutch Heart Foundation, CVON2015-08 ERASE (Optimal Early Recognition of Persons at High Risk of Aneurysmal Subarachnoid Hemorrhage). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 852173). The Swiss study was performed within the framework of the AneuX project supported by SystemsX.ch, and evaluated by the Swiss National Science Foundation (2014/261). Funding Information: We acknowledge the support from the Netherlands Cardiovascular Research Initiative: An initiative with support of the Dutch Heart Foundation, CVON2015-08 ERASE (Optimal Early Recognition of Persons at High Risk of Aneurysmal Subarachnoid Hemorrhage). This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. 852173). The Swiss study was performed within the framework of the AneuX project supported by SystemsX.ch, and evaluated by the Swiss National Science Foundation (2014/261). Publisher Copyright: © 2022 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
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