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.

我们结合来自未破裂颅内动脉瘤 (UIA) 患者前瞻性队列的个体患者数据 (IPD)，以评估家族性 UIA 患者比散发性 UIA 患者具有更高破裂风险的程度。

对于这项 IPD 荟萃分析，我们对截至 2020 年 12 月 1 日发表的研究进行了 Embase 和 PubMed 搜索。我们纳入了以下研究：(1) 具有前瞻性研究设计；(2) 包括 50 名或更多 UIA 患者；(3)研究了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) 动脉瘤破裂。包括具有可用 IPD 的队列。所有研究都包括访问其中一个研究中心的新诊断 UIA 患者。主要结果是动脉瘤破裂。排除多囊肾病和烟雾病患者。我们使用根据 PHASES 评分和吸烟调整的 Cox 比例风险回归模型比较了家族性与散发性 UIA 的破裂率。我们进行了 2 次分析：

我们汇集了来自 8 个具有低和中等偏倚风险的队列的 IPD。一级亲属被定义为 6 个队列中的父母、兄弟姐妹和儿童（29% 荷兰人，55% 芬兰人，15% 日本人），共有 2,297 名患者（17% 家族性，399 名患者），3,089 名 UIA 和 7,301 人年随访-向上。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）和 41 例散发病例（0.66%/人年；95% CI 0.48–0.89）；家族病例的调整后风险比 (HR) 为 2.56 (95% CI 1.18–5.56)。将不包括兄弟姐妹的 2 个队列添加为一级亲属后，共有 9,511 名患者，调整后的 HR 为 1.44（95% CI 0.86-2.40）。

家族性 UIA 破裂的风险比散发性 UIA 高 2.5 倍，风险范围为 1.2 至 5 倍。在评估 UIA 破裂的风险时，应考虑家族史。