Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.
Department of Neurology, Yale School of Medicine, New Haven, Connecticut.
JAMA Netw Open. 2024 Feb 5;7(2):e2355368. doi: 10.1001/jamanetworkopen.2023.55368.
Intracerebral hemorrhage (ICH) is a serious complication of brain arteriovenous malformation (AVM). Apolipoprotein E (APOE) ε4 is a well-known genetic risk factor for ICH among persons without AVM, and cerebral amyloid angiopathy is a vasculopathy frequently observed in APOE ε4 carriers that may increase the risk of ICH.
To assess whether APOE ε4 is associated with a higher risk of ICH in patients with a known AVM.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study including 412 participants was conducted in 2 stages (discovery and replication) using individual-level data from the UK Biobank (released March 2012 and last updated October 2023) and the All of Us Research Program (commenced on May 6, 2018, with its latest update provided in October 2023). The occurrence of AVM and ICH was ascertained at the time of enrollment using validated International Classification of Diseases, Ninth Revision and Tenth Revision, codes. Genotypic data on the APOE variants rs429358 and rs7412 were used to ascertain the ε status.
For each study, the association between APOE ε4 variants and ICH risk was assessed among patients with a known AVM by using multivariable logistic regression.
The discovery phase included 253 UK Biobank participants with known AVM (mean [SD] age, 56.6 [8.0] years, 119 [47.0%] female), of whom 63 (24.9%) sustained an ICH. In the multivariable analysis of 240 participants of European ancestry, APOE ε4 was associated with a higher risk of ICH (odds ratio, 4.58; 95% CI, 2.13-10.34; P < .001). The replication phase included 159 participants with known AVM enrolled in All of Us (mean [SD] age, 57.1 [15.9] years; 106 [66.7%] female), of whom 29 (18.2%) sustained an ICH. In multivariable analysis of 101 participants of European ancestry, APOE ε4 was associated with higher risk of ICH (odds ratio, 4.52; 95% CI, 1.18-19.38; P = .03).
The results of this cross-sectional study of patients from the UK Biobank and All of Us suggest that information on APOE ε4 status may help identify patients with brain AVM who are at particularly high risk of ICH and that cerebral amyloid angiopathy should be evaluated as a possible mediating mechanism of the observed association.
脑出血 (ICH) 是脑动静脉畸形 (AVM) 的严重并发症。载脂蛋白 E (APOE) ε4 是无 AVM 人群中 ICH 的一个众所周知的遗传风险因素，而脑淀粉样血管病是 APOE ε4 携带者中经常观察到的血管病，可能会增加 ICH 的风险。
评估 APOE ε4 是否与已知 AVM 患者的 ICH 风险增加相关。
设计、地点和参与者：这是一项使用 UK Biobank（于 2012 年 3 月发布，最后更新于 2023 年 10 月）和 All of Us 研究计划（于 2018 年 5 月 6 日开始，提供了最新更新于 2023 年 10 月）个体水平数据的两阶段（发现和复制）横断面研究。通过使用验证后的国际疾病分类，第九版和第十版代码，在入组时确定 AVM 和 ICH 的发生情况。使用 APOE 变体 rs429358 和 rs7412 的基因数据来确定 ε 状态。
对于每项研究，使用多变量逻辑回归评估了 APOE ε4 变体与已知 AVM 患者的 ICH 风险之间的关联。
发现阶段包括 253 名具有已知 AVM 的 UK Biobank 参与者（平均[SD]年龄 56.6[8.0]岁，119[47.0%]为女性），其中 63 名（24.9%）发生 ICH。在对 240 名欧洲血统参与者的多变量分析中，APOE ε4 与 ICH 风险增加相关（优势比，4.58；95%置信区间，2.13-10.34；P<0.001）。复制阶段包括 159 名参加 All of Us 的已知 AVM 参与者（平均[SD]年龄 57.1[15.9]岁，106[66.7%]为女性），其中 29 名（18.2%）发生 ICH。在对 101 名欧洲血统参与者的多变量分析中，APOE ε4 与 ICH 风险增加相关（优势比，4.52；95%置信区间，1.18-19.38；P=0.03）。
这项来自 UK Biobank 和 All of Us 的患者横断面研究的结果表明，APOE ε4 状态信息可能有助于识别 AVM 患者发生 ICH 的风险特别高，并且应评估脑淀粉样血管病作为观察到的关联的可能中介机制。
