title: Meta-analysis and systematic review of the predictive value of carotid plaque hemorrhage on cerebrovascular events by magnetic resonance imaging.
abstract: OBJECTIVE
  This study sought to conduct a systematic review and meta-analysis to determine precise estimates of the predictive value of carotid intraplaque hemorrhage (IPH) as determined by magnetic resonance imaging (MRI) for cerebrovascular events.
  
  
  BACKGROUND
  There is emerging evidence that MR-based carotid atherosclerotic plaque assessment identifies high-risk features associated with cerebrovascular events. However, available data are based on smaller samples with heterogeneous source populations despite a promising value for noninvasive risk stratification.
  
  
  METHODS
  We searched PubMed, EMBASE, and the Cochrane Library through September 2012 for studies that followed >35 individuals after baseline MRI. Independent observers abstracted information on populations, MR techniques, outcomes, and study quality. Risk estimates of the presence of IPH for cerebrovascular events were derived in random effects regression analysis, and causes of heterogeneity were determined in meta-regression analysis.
  
  
  RESULTS
  We identified 8 eligible studies including 689 participants who underwent carotid MRI. The prevalence of IPH at baseline was high (49.0%). Over a median follow-up of 19.6 months, a total of 108 cerebrovascular events occurred (15.7% event rate). The presence of IPH was associated with an ∼6-fold higher risk for events (hazard ratio [HR]: 5.69; 95% confidence interval [CI]: 2.98 to 10.87). The annualized event rate in subjects with detectable IPH was 17.71% compared with 2.43% in patients without IPH. Meta-regression analysis showed symptomatic subjects had higher risks as compared with asymptomatic subjects (HR: 11.71, 95% CI: 5.17 to 26.48 vs. HR: 3.50, 95% CI: 2.59 to 4.73, p = 0.0065), Also, differences were observed for sex and sample size (all p < 0.01), with moderate visual publication bias due to missing smaller sample-size studies (p = 0.18).
  
  
  CONCLUSIONS
  Presence of IPH on MRI strongly predicts cerebrovascular events. Homogenization of future studies is warranted to allow for sufficient assessment of level of evidence for intervention trials.
authors.affiliation: Institute of Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich, Germany. Electronic address: tobias.saam@med.lmu.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Saam
authors.affiliation: Institute of Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Hetterich
authors.affiliation: Institute of Biomedical Epidemiology, Ludwig-Maximilians-University Hospital Munich, Munich, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Hoffmann
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Chun
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Institute for Stroke and Dementia Research, Ludwig-Maximilians-University Hospital Munich, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: Department of Neurology, Technische Universität München, Munich, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Poppert
authors.affiliation: Division of Vascular and Endovascular Surgery, Ludwig-Maximilians-University Hospital Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Koeppel
authors.affiliation: Division of Vascular Medicine, Medical Clinic and Policlinic IV, Ludwig-Maximilians-University Hospital Munich, Munich, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: Institute of Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich, Germany.
authors.forename: Maximilian F
authors.initials: MF
authors.lastname: Reiser
authors.affiliation: Institute of Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Bamberg
mesh_terms: D002340:Carotid Artery Diseases / Q000150:complications* / Q000175:diagnosis*; D002561:Cerebrovascular Disorders / Q000209:etiology*; D006470:Hemorrhage / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D058226:Plaque, Atherosclerotic / Q000150:complications*; D011237:Predictive Value of Tests; D011379:Prognosis
keywords: CI; HR; IPH; MRI; TIA; confidence interval; hazard ratio; intraplaque hemorrhage; magnetic resonance imaging; meta-analysis; noninvasive imaging; plaque hemorrhage; prognostic value; transient ischemic attack