Difference in rupture risk between familial and sporadic intracranial aneurysms an individual patient data meta-analysis

Charlotte C.M. Zuurbier, Liselore A. Mensing, Marieke J.H. Wermer, Seppo Juvela, Antti E. Lindgren, Timo Koivisto, Juha E. J¨äaskel¨ainen, Tomosato Yamazaki, Rob Molenberg, J. Marc C. Van Dijk, Maarten Uyttenboogaart, Marlien Aalbers, Akio Morita, Shinjiro Tominari, Hajime Arai, Kazuhiko Nozaki, Yuichi Murayama, Toshihiro Ishibashi, Hiroyuki Takao, Gabriel J.E. RinkelJacoba P. Greving, Ynte M. Ruigrok*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background and Objectives We combined individual patient data (IPD) fromprospective cohorts of patients with unruptured intracranial aneurysms (UIAs) to assess to what extent patients with familial UIA have a higher rupture risk than those with sporadic UIA. Methods For this IPD meta-analysis, we performed an Embase and PubMed search for studies published up to December 1, 2020. We included studies that (1) had a prospective study design; (2) included 50 or more patients with UIA; (3) studied the natural course of UIA and risk factors for aneurysm rupture including family history for aneurysmal subarachnoid haemorrhage and UIA; and (4) had aneurysm rupture as an outcome. Cohorts with available IPD were included. All studies included patients with newly diagnosed UIA visiting one of the study centers. The primary outcome was aneurysmal rupture. Patients with polycystic kidney disease and moyamoya disease were excluded. We compared rupture rates of familial vs sporadic UIA using a Cox proportional hazard regression model adjusted for PHASES score and smoking. We performed 2 analyses: (1) only studies defining first-degree relatives as parents, children, and siblings and (2) all studies, including those in which first-degree relatives are defined as only parents and children, but not siblings. Results We pooled IPD from 8 cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings, and children in 6 cohorts (29% Dutch, 55% Finnish, 15% Japanese), totaling 2,297 patients (17% familial, 399 patients) with 3,089 UIAs and 7,301 person-years follow-up. Rupture occurred in 10 familial cases (rupture rate: 0.89%/person-year; 95% confidence interval [CI] 0.45-1.59) and 41 sporadic cases (0.66%/person-year; 95% CI 0.48-0.89); adjusted hazard ratio (HR) for familial cases 2.56 (95% CI 1.18-5.56). After adding the 2 cohorts excluding siblings as first-degree relatives, resulting in 9,511 patients, the adjusted HR was 1.44 (95% CI 0.86-2.40). Discussion The risk of rupture of UIA is 2.5 times higher, with a range from a 1.2 to 5 times higher risk, in familial than in sporadic UIA. When assessing the risk of rupture in UIA, family history should be taken into account.

Original languageEnglish
Pages (from-to)E2195-E2203
JournalNeurology
Volume97
Issue number22
DOIs
Publication statusPublished - 30 Nov 2021

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