Background and Purpose:For survivors of oral anticoagulation therapy (OAT)–associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E (APOE) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest.Methods:Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE-MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis.Results:Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P<0.05). Combining APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P=0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH.Conclusions:Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE-MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.

中文翻译：

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结合影像学和遗传学预测抗凝相关脑出血的复发。

背景和目的：对于血栓栓塞高风险的口​​服抗凝治疗 (OAT) 相关脑出血 (OAT-ICH) 幸存者，必须权衡恢复 OAT 的益处与复发性出血性卒中风险的增加。载脂蛋白 E ( APOE ) 基因的 ε2/ε4 等位基因、MRI 定义的皮质浅表铁质沉着症和脑微出血是复发性 ICH 最有效的危险因素。我们试图确定是否结合 MRI 标记和APOE基因型可以通过识别 OAT 恢复风险最高的 ICH 幸存者来产生临床影响。方法：对 OAT-ICH 幸存者的 2 项纵向队列研究的数据进行联合分析：（1）MGH-ICH 研究（马萨诸塞州总医院 ICH）和(2) ERICH 研究的纵向组成部分（脑出血的种族/种族变异）。我们评估了 MRI 标志物和APOE基因型是否可以预测 ICH 复发。然后，我们使用分类和回归树分析开发并验证了一种组合APOE -MRI 分类方案来预测 ICH 复发。结果：皮质浅表铁质沉着症、脑微出血和APOE ε2/ε4 变异与 OAT-ICH 后 ICH 复发独立相关。全P<0.05)。结合APOE基因型和 MRI 数据可以改善 ICH 复发的预测（Harrell C：0.79 对 0.55 单独的临床数据，P = 0.033）。在 MGH（训练）数据集中，CSS、脑微出血和APOE ε2/ε4 将 ICH 复发的可能性分为高、中和低风险类别。在 ERICH（验证）数据集中，高、中、低风险个体的年 ICH 复发率分别为 6.6%、2.5% 和 0.9%，预测复发的总曲线下面积为 0.91 ICH.结论：结合 MRI 和APOE基因型将 ICH 复发的可能性分为高、中和低风险。如果在前瞻性研究中得到证实，这种组合的APOE-MRI 分类方案可能证明对选择 ICH 后恢复 OAT 的个体有用。