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

Kristin Schwab; Zora DiPucchio; Tyler Behymer; Jennifer Osborne; Misty Morgan; Charles J Moomaw; Michael L James; Steven M Greenberg; Anand Viswanathan; M. Edip Gurol; Bradford B Worrall; Alessandro Biffi; Sebastian Urday; Fernando D Testai; Jacob L McCauley; Patryk Kubiszewski; Lee Gilkerson; Guido J Falcone; Padmini Sekar; Carl D Langefeld; Axana Rodriguez-Torres; Christopher D Anderson; Margaret Bettin; Hooman Kamel; Daniel Woo; Andreas Charidimou; Marco Pasi; Kevin N Sheth; Christina Kourkoulis; Jonathan Rosand

doi:10.1161/STROKEAHA.120.028310

Back

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

Journal article

Peer reviewed

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

Kristin Schwab, Zora DiPucchio, Tyler Behymer, Jennifer Osborne, Misty Morgan, Charles J Moomaw, Michael L James, Steven M Greenberg, Anand Viswanathan, M. Edip Gurol, …

Stroke (1970), Vol.51(7), pp.2153-2160

2020-07

DOI: https://doi.org/10.1161/STROKEAHA.120.028310

PMID: 32517581

Abstract

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.

Metrics

40 Record Views

14 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.60 Dementia
Web Of Science research areas: Clinical Neurology; Peripheral Vascular Disease
ESI research areas: Neuroscience & Behavior

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: Combining Imaging and Genetics to Predict Recurrence of Anticoagulation-Associated Intracerebral Hemorrhage
Creators: Kristin Schwab - Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston
Zora DiPucchio - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston
Tyler Behymer - Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, OH (L.G., P.S., T.B., J.O., M.M., C.J.M., D.W.)
Jennifer Osborne - Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, OH (L.G., P.S., T.B., J.O., M.M., C.J.M., D.W.)
Misty Morgan - Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, OH (L.G., P.S., T.B., J.O., M.M., C.J.M., D.W.)
Charles J Moomaw - Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, OH (L.G., P.S., T.B., J.O., M.M., C.J.M., D.W.)
Michael L James - Department of Anesthesiology, Duke University, Durham, NC (M.L.J.)
Steven M Greenberg - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston
Anand Viswanathan - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston
M. Edip Gurol - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston
Alessandro Biffi - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Center for Genomic Medicine (A.B., P.K., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston., Henry and Allison McCance Center for Brain Health (A.B., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston
Bradford B Worrall - Department of Neurology, University of Virginia Health System, Charlottesville (M.B., B.B.W.)
Sebastian Urday - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston
Fernando D Testai - Department of Neurology and Rehabilitation, University of Illinois at Chicago College of Medicine, Chicago (F.D.T.)
Patryk Kubiszewski - Center for Genomic Medicine (A.B., P.K., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston
Jacob L McCauley - Center for Genome Technology and Biorepository Facility, University of Miami, Miller School of Medicine, FL (J.L.M.)
Lee Gilkerson - Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, OH (L.G., P.S., T.B., J.O., M.M., C.J.M., D.W.)
Guido J Falcone - Department of Neurology, Yale University School of Medicine, New Haven, CT (G.J.F.)
Padmini Sekar - Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, OH (L.G., P.S., T.B., J.O., M.M., C.J.M., D.W.)
Carl D Langefeld - Department of Biostatistics and Data Sciences, Wake Forest University, Winston-Salem, NC (C.D.L.)
Axana Rodriguez-Torres - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston
Christopher D Anderson - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Center for Genomic Medicine (A.B., P.K., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston., Henry and Allison McCance Center for Brain Health (A.B., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston., Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge (C.D.A., J.R.)
Margaret Bettin - Department of Neurology, University of Virginia Health System, Charlottesville (M.B., B.B.W.)
Hooman Kamel - Department of Neurology, Weill Cornell School of Medicine, New York, NY (H.K.)
Andreas Charidimou - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston
Daniel Woo - Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, OH (L.G., P.S., T.B., J.O., M.M., C.J.M., D.W.)
Marco Pasi - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston
Kevin N Sheth
Jonathan Rosand - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Center for Genomic Medicine (A.B., P.K., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston., Henry and Allison McCance Center for Brain Health (A.B., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston., Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge (C.D.A., J.R.)
Christina Kourkoulis - Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston., Center for Genomic Medicine (A.B., P.K., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston., Hemorrhagic Stroke Research Program (A.B., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A, J.R.), Massachusetts General Hospital, Boston., Henry and Allison McCance Center for Brain Health (A.B., C.K., C.D.A., J.R.), Massachusetts General Hospital, Boston
Publication Details: Stroke (1970), Vol.51(7), pp.2153-2160
Academic Unit: Miller School of Medicine; John P. Hussman Institute for Human Genomics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 32517581
Record Identifier: 991031578295802976