Online citations, reference lists, and bibliographies.
← Back to Search

Combining Imaging And Genetics To Predict Recurrence Of Anticoagulation-Associated Intracerebral Hemorrhage

A. Biffi, Sebastian Urday, Patryk Kubiszewski, Lee A Gilkerson, P. Sekar, A. Rodriguez-Torres, Margaret Bettin, A. Charidimou, M. Pasi, Christina E. Kourkoulis, K. Schwab, Zora Y. DiPucchio, Tyler P. Behymer, J. Osborne, M. Morgan, C. Moomaw, M. L. James, S. Greenberg, A. Viswanathan, M. Gurol, B. Worrall, F. Testai, J. McCauley, G. Falcone, C. Langefeld, C. Anderson, H. Kamel, D. Woo, K. Sheth, J. Rosand
Published 2020 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
Supplemental Digital Content is available in the text. 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.
This paper references
Comparison of Methods for Estimating the Number of True Null Hypotheses in Multiplicity Testing
H. Hsueh (2003)
Variants at APOE influence risk of deep and lobar intracerebral hemorrhage
A. Biffi (2010)
Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy
J. Linn (2010)
Warfarin-related intraventricular hemorrhage
A. Biffi (2011)
The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study Protocol
D. Woo (2013)
Effect of warfarin on intracranial hemorrhage incidence and fatal outcomes.
D. Witt (2013)
Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration
J. Wardlaw (2013)
Incidence of Symptomatic Hemorrhage in Patients With Lobar Microbleeds
Ellis S. van Etten (2014)
APOE ε variants increase risk of warfarin-related intracerebral hemorrhage
G. Falcone (2014)
Identifying Homogeneous Subgroups in Neurological Disorders
L. G. Tanadini (2014)
International Stroke Genetics Consortium. APOE ε variants increase risk of warfarinrelated intracerebral hemorrhage
GJ Falcone (2014)
Association Between Blood Pressure Control and Risk of Recurrent Intracerebral Hemorrhage.
A. Biffi (2015)
Cerebral amyloid angiopathy with and without hemorrhage
A. Charidimou (2015)
Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage
S. Martínez-Ramírez (2015)
Comparing two correlated C indices with right-censored survival outcome: a one-shot nonparametric approach.
L. Kang (2015)
Cerebral amyloid angiopathy with and without hemorrhage: evidence for different disease
A Charidimou (2015)
Total Magnetic Resonance Imaging Burden of Small Vessel Disease in Cerebral Amyloid Angiopathy: An Imaging-Pathologic Study of Concept Validation.
A. Charidimou (2016)
Restarting Anticoagulant Therapy After Intracranial Hemorrhage: A Systematic Review and Meta-Analysis
S. Murthy (2017)
Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update
S. J. An (2017)
Oral Anticoagulation and Functional Outcome after Intracerebral Hemorrhage
A. Biffi (2017)
Hypertension and intracerebral hemorrhage recurrence among white, black, and Hispanic individuals
A. Rodriguez-Torres (2018)
Cerebral small vessel disease and risk of incident stroke, dementia and depression, and all-cause mortality: A systematic review and meta-analysis
Sytze P. Rensma (2018)
Cerebral amyloid angiopathy, cerebral microbleeds and implications for anticoagulation decisions: The need for a balanced approach
A. Charidimou (2018)
Cerebral small vessel disease and risk of incident stroke, dementia and depression, and allcause mortality: a systematic review and meta-analysis
SP Rensma (2018)

This paper is referenced by
Semantic Scholar Logo Some data provided by SemanticScholar