title: Recurrent hemorrhage risk and mortality in hereditary and sporadic cerebral amyloid angiopathy.
abstract: OBJECTIVE
  To determine whether hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), a monogenetic disease model for the sporadic variant of amyloid angiopathy (sCAA), has a comparable recurrent intracerebral hemorrhage (ICH) risk and mortality after a first symptomatic ICH.
  
  
  METHODS
  We included patients with HCHWA-D from the Leiden University Medical Center and patients with sCAA from the Massachusetts General Hospital in a cohort study. Baseline characteristics, hemorrhage recurrence, and short- and long-term mortality were compared. Hazard ratios (HRs) adjusted for age and sex were calculated with Cox regression analyses.
  
  
  RESULTS
  We included 58 patients with HCHWA-D and 316 patients with sCAA. Patients with HCHWA-D had fewer cardiovascular risk factors (≥1 risk factor 24% vs 70% in sCAA) and were younger at the time of presenting hemorrhage (mean age 54 vs 72 years in sCAA). Eight patients (14%) with HCHWA-D and 46 patients (15%) with sCAA died before 90 days. During a mean follow-up time of 5 ± 4 years (total 1,550 person-years), the incidence rate of recurrent ICH in patients with HCHWA-D was 20.9 vs 8.9 per 100 person-years in sCAA. Patients with HCHWA-D had a long-term mortality of 8.2 vs 8.4 per 100 person-years in patients with sCAA. After adjustments, patients with HCHWA-D had a higher risk of recurrent ICH (HR 2.8; 95% confidence interval 1.6-4.9; p < 0.001) and a higher long-term mortality (HR 2.8; 95% confidence interval 1.5-5.2; p = 0.001).
  
  
  CONCLUSIONS
  Patients with HCHWA-D have worse long-term prognosis after a first ICH than patients with sCAA. The absence of cardiovascular risk factors in most patients with HCHWA-D suggests that vascular amyloid is responsible for the recurrent hemorrhages. HCHWA-D is therefore a pure form of cerebral amyloid angiopathy with an accelerated clinical course and provides a good model to study the pathophysiology and future therapeutic interventions of amyloid-related hemorrhages.
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston. e.s.van_etten@lumc.nl.
authors: Ellis S
authors: ES
authors: van Etten
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: M Edip
authors: ME
authors: Gurol
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Jeroen
authors: J
authors: van der Grond
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Joost
authors: J
authors: Haan
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Anand
authors: A
authors: Viswanathan
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Kristin M
authors: KM
authors: Schwab
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Alison M
authors: AM
authors: Ayres
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Ale
authors: A
authors: Algra
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Jonathan
authors: J
authors: Rosand
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Mark A
authors: MA
authors: van Buchem
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Gisela M
authors: GM
authors: Terwindt
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Steven M
authors: SM
authors: Greenberg
authors: From the Departments of Neurology (E.S.v.E., J.H., G.M.T., M.J.H.W.), Radiology (J.v.d.G., M.A.v.B.), and Clinical Epidemiology (A.A.), Leiden University Medical Center; Department of Neurology (J.H.), Alrijne Hospital; Department of Neurology and Neurosurgery (A.A.), Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Hemorrhagic Stroke Research Program (M.E.G., A.V., K.M.S., A.M.A., S.M.G.), Department of Neurology, Massachusetts General Hospital Stroke Research Center; and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
authors: Marieke J H
authors: MJ
authors: Wermer
mesh_terms: D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging; D016657:Cerebral Amyloid Angiopathy / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000401:mortality*; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000401:mortality*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor