TY - JOUR
T1 - Difference in Rupture Risk Between Familial and Sporadic Intracranial Aneurysms An Individual Patient Data Meta-analysis
AU - Zuurbier, Charlotte C. M.
AU - Mensing, Liselore A.
AU - Wermer, Marieke J. H.
AU - Juvela, Seppo
AU - Lindgren, Antti E.
AU - Koivisto, Timo
AU - Jaaskelainen, Juha E.
AU - Yamazaki, Tomosato
AU - Molenberg, Rob
AU - van Dijk, J. Marc C.
AU - Uyttenboogaart, Maarten
AU - Aalbers, Marlien
AU - Morita, Akio
AU - Tominari, Shinjiro
AU - Arai, Hajime
AU - Nozaki, Kazuhiko
AU - Murayama, Yuichi
AU - Ishibashi, Toshihiro
AU - Takao, Hiroyuki
AU - Rinkel, Gabriel J. E.
AU - Greving, Jacoba P.
AU - Ruigrok, Ynte M.
N1 - © 2021 American Academy of Neurology.
PY - 2021/11/30
Y1 - 2021/11/30
N2 - OBJECTIVE: We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIA) 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 versus sporadic UIA using a Cox proportional hazard regression model adjusted for the PHASES score and smoking. We performed two 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 eight cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings and children in six cohorts (29% Dutch, 55% Finnish, 15% Japanese), totalling 2,297 patients (17% familial, 399 patients) with 3,089 UIA and 7,301 person-years follow-up. Rupture occurred in 10 familial patients (rupture rate: 0·89%/person-year; 95% CI:0·45-1·59) and 41 sporadic patients (0·66%/person-year; 95% CI:0·48-0·89); adjusted HR for familial patients 2·56 (95% CI: 1·18-5·56). After adding also the two cohorts excluding siblings as first-degree relatives resulting in 9,511 patients the adjusted HR was 1·44 (95% CI: 0·86-2·40).CONCLUSION: The risk of rupture of UIA is two and a half 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.
AB - OBJECTIVE: We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIA) 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 versus sporadic UIA using a Cox proportional hazard regression model adjusted for the PHASES score and smoking. We performed two 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 eight cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings and children in six cohorts (29% Dutch, 55% Finnish, 15% Japanese), totalling 2,297 patients (17% familial, 399 patients) with 3,089 UIA and 7,301 person-years follow-up. Rupture occurred in 10 familial patients (rupture rate: 0·89%/person-year; 95% CI:0·45-1·59) and 41 sporadic patients (0·66%/person-year; 95% CI:0·48-0·89); adjusted HR for familial patients 2·56 (95% CI: 1·18-5·56). After adding also the two cohorts excluding siblings as first-degree relatives resulting in 9,511 patients the adjusted HR was 1·44 (95% CI: 0·86-2·40).CONCLUSION: The risk of rupture of UIA is two and a half 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.
KW - UNRUPTURED CEREBRAL ANEURYSMS
KW - SUBARACHNOID HEMORRHAGE
KW - NATURAL-HISTORY
KW - LONG-TERM
KW - PREDICTION
KW - 1ST-DEGREE
U2 - 10.1212/WNL.0000000000012885
DO - 10.1212/WNL.0000000000012885
M3 - Article
C2 - 34670818
SN - 0028-3878
VL - 97
SP - E2195-E2203
JO - Neurology
JF - Neurology
IS - 22
ER -