Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy

Objective: To identify and compare clinical and neuroimaging predictors of primary lobar intracerebral hemorrhage (ICH) recurrence, assessing their relative contributions to recurrent ICH. Methods: Subjects were consecutive survivors of primary ICH drawn from a single-center prospective cohort study. Baseline clinical, imaging, and laboratory data were collected. Survivors were followed prospectively for recurrent ICH and intercurrent aspirin and warfarin use, including duration of exposure. Cox proportional hazards models were used to identify predictors of recurrence stratified by ICH location, with aspirin and warfarin exposures as time-dependent variables adjusting for potential confounders. Results: A total of 104 primary lobar ICH survivors were enrolled. Recurrence of lobar ICH was associated with previous ICH before index event (hazard ratio [HR] 7.7, 95% confidence interval [CI] 1.4–15.7), number of lobar microbleeds (HR 2.93 with 2–4 microbleeds present, 95% CI 1.3–4.0; HR = 4.12 when ≥5 microbleeds present, 95% CI 1.6–9.3), and presence of CT-defined white matter hypodensity in the posterior region (HR 4.11, 95% CI 1.01–12.2). Although aspirin after ICH was not associated with lobar ICH recurrence in univariate analyses, in multivariate analyses adjusting for baseline clinical predictors, it independently increased the risk of ICH recurrence (HR 3.95, 95% CI 1.6–8.3, p = 0.021). Conclusions: Recurrence of lobar ICH is associated with previous microbleeds or macrobleeds and posterior CT white matter hypodensity, which may be markers of severity for underlying cerebral amyloid angiopathy. Use of an antiplatelet agent following lobar ICH may also increase recurrence risk.

[1]  A. Hofman,et al.  Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam Scan Study. , 2009, Archives of neurology.

[2]  Wi-Sun Ryu,et al.  Cerebral microbleeds are a risk factor for warfarin-related intracerebral hemorrhage , 2009, Neurology.

[3]  Istvan Csapo,et al.  Spatial Distribution of White-Matter Hyperintensities in Alzheimer Disease, Cerebral Amyloid Angiopathy, and Healthy Aging , 2008, Stroke.

[4]  David W. Hosmer,et al.  Applied Survival Analysis: Regression Modeling of Time-to-Event Data , 2008 .

[5]  O. Lopez,et al.  Cerebral microbleeds in the population based AGES-Reykjavik study: prevalence and location , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[6]  Mario Zuccarello,et al.  Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association , 2015, Stroke.

[7]  K. Lunetta,et al.  Heritability of Magnetic Resonance Imaging (MRI) Traits in Alzheimer Disease Cases and Their Siblings in the MIRAGE Study , 2007, Alzheimer disease and associated disorders.

[8]  Eric E. Smith,et al.  Antiplatelet use after intracerebral hemorrhage , 2006, Neurology.

[9]  Nobuyuki Yasui,et al.  [Intracerebral hemorrhage]. , 2006, Nihon rinsho. Japanese journal of clinical medicine.

[10]  Eric E. Smith,et al.  Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy , 2005, Annals of neurology.

[11]  S. Greenberg,et al.  White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage , 2004, Neurology.

[12]  S. Greenberg,et al.  Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage , 2004, Neurology.

[13]  Eric E. Smith,et al.  Hemorrhage Burden Predicts Recurrent Intracerebral Hemorrhage After Lobar Hemorrhage , 2004, Stroke.

[14]  D. Singer,et al.  The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. , 2004, Archives of internal medicine.

[15]  Eric E. Smith,et al.  Clinical diagnosis of cerebral amyloid angiopathy: Validation of the Boston Criteria , 2003, Current atherosclerosis reports.

[16]  D. Singer,et al.  Can Patients Be Anticoagulated After Intracerebral Hemorrhage?: A Decision Analysis , 2003, Stroke.

[17]  Jia Liu,et al.  Asymptomatic microbleeds as a risk factor for aspirin-associated intracerebral hemorrhages , 2003, Neurology.

[18]  J. Szaflarski,et al.  Genetic and Environmental Risk Factors for Intracerebral Hemorrhage: Preliminary Results of a Population-Based Study , 2002, Stroke.

[19]  O. Benavente,et al.  Recurrent brain hemorrhage is more frequent than ischemic stroke after intracranial hemorrhage , 2001, Neurology.

[20]  S. Greenberg,et al.  Clinical diagnosis of cerebral amyloid angiopathy: Validation of the Boston Criteria , 2003, Current atherosclerosis reports.

[21]  S. Greenberg,et al.  Warfarin-associated hemorrhage and cerebral amyloid angiopathy , 2000, Neurology.

[22]  J. Woo,et al.  Aspirin-associated intracerebral hemorrhage , 2000, Neurology.

[23]  K. Furie,et al.  Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. , 2000, The New England journal of medicine.

[24]  S. Greenberg,et al.  Association of apolipoprotein E ϵ2 and vasculopathy in cerebral amyloid angiopathy , 1998, Neurology.

[25]  Bradley T. Hyman,et al.  Apolipoprotein E ε4 Is Associated With the Presence and Earlier Onset of Hemorrhage in Cerebral Amyloid Angiopathy , 1996 .

[26]  S. Finklestein,et al.  Petechial hemorrhages accompanying lobar hemorrhage , 1996, Neurology.

[27]  B T Hyman,et al.  Apolipoprotein E epsilon 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. , 1996, Stroke.

[28]  Raul G Nogueira,et al.  Spontaneous intracerebral hemorrhage. , 1992, Neurosurgery clinics of North America.

[29]  P. Koudstaal,et al.  Grading white matter lesions on CT and MRI: a simple scale. , 1990, Journal of neurology, neurosurgery, and psychiatry.