Zuurbier Charlotte C M, Mensing Liselore A, Wermer Marieke J H, Juvela Seppo, Lindgren Antti E, Koivisto Timo, Jääskeläinen Juha E, Yamazaki Tomosato, Molenberg Rob, van Dijk J Marc C, Uyttenboogaart Maarten, Aalbers Marlien, Morita Akio, Tominari Shinjiro, Arai Hajime, Nozaki Kazuhiko, Murayama Yuichi, Ishibashi Toshihiro, Takao Hiroyuki, Rinkel Gabriel J E, Greving Jacoba P, Ruigrok Ynte M
From the Department of Neurology and Neurosurgery, UMC Utrecht Brain Center (C.C.M.Z., L.A.M., G.J.E.R., Y.M.R.), and Julius Centre for Health Sciences and Primary Care (J.P.G.), University Medical Center Utrecht; Department of Neurology (M.J.H.W.), Leiden University Medical Center, the Netherlands; Department of Clinical Neurosciences (S.J.), University of Helsinki; Neurosurgery of NeuroCenter (A.E.L., T.K., J.E.J.), University of Eastern Finland, Kuopio, Finland; Department of Neurosurgery (T.Y.), National Hospital Organization, Mito Medical Center, Japan; Departments of Neurosurgery (R.M., J.M.C.v.D., M.U., M.A.), University Medical Center Groningen, the Netherlands; University of Tokyo-Nippon Medical School (A.M.); Department of Health Informatics, School of Public Health (S.T.), Kyoto University; Department of Neurosurgery (H.A.), Juntendo University Medical School, Tokyo; Department of Neurosurgery (K.N.), Shiga University of Medical Science; and Department of Endovascular Neurosurgery (Y.M., T.I., H.T.), Tokyo Jikei University School of Medicine, Japan.
Neurology. 2021 Nov 30;97(22):e2195-e2203. doi: 10.1212/WNL.0000000000012885. Epub 2021 Oct 20.
We combined individual patient data (IPD) from prospective 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.
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.
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).
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.
我们合并了未破裂颅内动脉瘤（UIA）患者前瞻性队列的个体患者数据（IPD），以评估家族性UIA患者的破裂风险比散发性UIA患者高多少。
对于这项IPD荟萃分析，我们在Embase和PubMed上检索了截至2020年12月1日发表的研究。我们纳入的研究需满足以下条件：（1）具有前瞻性研究设计；（2）纳入50名或更多UIA患者；（3）研究UIA的自然病程和动脉瘤破裂的危险因素，包括动脉瘤性蛛网膜下腔出血和UIA的家族史；（4）以动脉瘤破裂作为结局。纳入有可用IPD的队列。所有研究均纳入了在其中一个研究中心就诊的新诊断UIA患者。主要结局是动脉瘤破裂。排除多囊肾病和烟雾病患者。我们使用调整了PHASES评分和吸烟情况的Cox比例风险回归模型比较家族性和散发性UIA的破裂率。我们进行了两项分析：（1）仅纳入将一级亲属定义为父母、子女和兄弟姐妹的研究；（2）所有研究，包括那些将一级亲属仅定义为父母和子女但不包括兄弟姐妹的研究。
我们汇总了8个偏倚风险低和中等的队列的IPD。在6个队列（29%为荷兰人、55%为芬兰人、15%为日本人）中，一级亲属被定义为父母、兄弟姐妹和子女，共有2297例患者（17%为家族性，399例患者），有3089个UIA，随访7301人年。10例家族性病例发生破裂（破裂率：0.89%/人年；95%置信区间[CI]0.45 - 1.59），41例散发性病例发生破裂（0.66%/人年；95%CI 0.48 - 0.89）；家族性病例的调整风险比（HR）为2.56（95%CI 1.18 - 5.56）。在加入另外2个不将兄弟姐妹视为一级亲属的队列后，患者总数达到9511例，调整后的HR为1.44（95%CI 0.86 - 2.40）。
家族性UIA的破裂风险比散发性UIA高2.5倍，风险范围为高1.2至5倍。在评估UIA的破裂风险时，应考虑家族史。
