Combining Imaging and Genetics to Predict Recurrence of Anticoagulation-Associated Intracerebral Hemorrhage.

Abstract

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 <i>apolipoprotein E</i> (<i>APOE</i>) 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 <i>APOE</i> genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. 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 <i>APOE</i> genotype predict ICH recurrence. We then developed and validated a combined <i>APOE</i>-MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. Cortical superficial siderosis, cerebral microbleed, and <i>APOE</i> ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all <i>P</i><0.05). Combining <i>APOE</i> genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, <i>P</i>=0.033). In the MGH (training) data set, CSS, cerebral microbleed, and <i>APOE</i> 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. Combining MRI and <i>APOE</i> genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined <i>APOE</i>-MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.