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August 17, 2011

Ultrasonic plaque echolucency and emboli signals predict stroke in asymptomatic carotid stenosis

August 23, 2011 issue
77 (8) 751-758

Abstract

Objectives:

Better methods are required to identify patients with asymptomatic carotid stenosis (ACS) at risk of future stroke. Two potential markers of high risk are echolucent plaque morphology on carotid ultrasound and embolic signals (ES) in the ipsilateral middle cerebral artery on transcranial Doppler ultrasound (TCD). We explored the predictive value of a score based on these 2 measures in the prospective, observational, international multicenter Asymptomatic Carotid Emboli Study.

Methods:

A total of 435 recruited subjects with ACS ≥70% had baseline ultrasound images and TCD data available. Subjects were prospectively followed up for 2 years.

Results:

A total of 164 (37.7%) plaques were graded as echolucent. Plaque echolucency at baseline was associated with an increased risk of ipsilateral stroke alone (hazard ratio [HR] 6.43, 95% confidence interval [CI] 1.36–30.44, p = 0.019). A combined variable of plaque echolucency and ES positivity at baseline was associated with a markedly increased risk of ipsilateral stroke alone (HR 10.61, 95% CI 2.98–37.82, p = 0.0003). This association remained significant after controlling for risk factors, degree of carotid stenosis, and antiplatelet medication.

Conclusions:

Plaque morphology assessed using a simple, and clinically applicable, visual rating scale predicts ipsilateral stroke risk in ACS. The combination of ES detection and plaque morphology allows a greater prediction than either measure alone and identifies a high-risk group with an annual stroke risk of 8%, and a low-risk group with a risk of <1% per annum. This risk stratification may prove useful in the selection of patients with ACS for endarterectomy. Neurology® 2011;77:751–758

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Supplementary Material

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COINVESTIGATORS

Participating centers of coinvestigators recruiting patients and number of patients recruited were as follows: Bretonneau Hospital, France (Francois Tranquart MD, PhD, and Aurore Bleuzen, MD), 2; Charing Cross Hospital, UK (Prof. Alun Davies, FRCS), 6; Harbin Medical University, China (Prof. Song-Bin Qu, MD), 20; Institute of Psychiatry and Neurology, Poland (Prof. Anna Czlonkowskia, PhD, Anna Rozenfeld, PhD, Anna Piorkowska, MD, and Marta Skowronska, PhD), 5; James Connolly Memorial Hospital, Ireland (Dermot Fitzgerald, MD, PhD, and Nuala McMahon, MD), 8; JW Goethe University, Germany (Matthias Sitzer, MD, PhD, and Oliver Singer, MD), 14; Kings College Hospital, UK (Paul Baskerville, FRCS, Colin Deane, PhD, and David Goss, PhD), 31; Leicester Royal Infirmary, UK (Prof. Ross Naylor, MD, FRCS, and Jo Walker, PgC[Vasc]), 23; Martini Ziekenhuis Groningen, the Netherlands (Arjen Schaafsma, MD, PhD, and An Fokkens), 84; Prince of Wales Hospital, Hong Kong (Prof. Lawrence Wong, FRCP, Sunny Qing Hao, MD, and Roxanna Liu, MD), 3; Rabin Medical Centre, Israel (Jonathan Streifler, MD, FAHA, and Tilda Sabah, MD), 7; San Martino Hospital Genova, Italy (Giulia Brusa, MD, Vittorio Montano, MD, and Gian Andrea Ottonello, MD), 21; Singapore General Hospital Campus, National Neuroscience Institute, Singapore (Hui-Meng Chang, MRCP, FAMS, Moi Pin Lee, RVT, Meng Cheong Wong, FRCP, FAAN, and Christopher P.L.H. Chen, FAMS, FRCP), 15; State Medical Academy, GA (Marina Alpaidze, MD, and Nana Meterveli, PhD), 12; St George's University of London, UK (Prof. Hugh Markus, FRCP, and Jennifer Siegel, BSc), 71; Tel Aviv Sourasky Medical Centre, Israel (Prof. Natan Bornstein, Alex Gur, MD, PhD, and Sigal Lorenz, MD), 46; UCL Institute of Neurology, UK (Prof. Martin M. Brown, FRCP), 1; UCLA School of Medicine, USA (Jeffrey Saver, MD, and Gina Paek, BSc), 5; University Hospital Josep Trueta, IdIBGi Spain (Joaquin Serena, MD, PhD, and Xavier Ustrell, MD), 19; University Hospital of South Manchester, UK (Prof Charles McCollum, ChB, MD, FRCS, Sarah Welsh, BSc, and Zoe Bonner, BSc), 26; University Hospital Zagreb, Croatia (Prof. Vida Demarin, MD, PhD, FAAN, FAHA, FESO, and Asst. Prof. Vlasta Vukovic Cvetković, MD, PhD), 12; University Medical Centre Ljubljana, Neurology Clinic, Clinical Department of Vascular and Intensive Neurology, Slovenia (Bojana Zvan, MD, PhD, and Janja Pretnar, MD, PhD), 4; University of Dusseldorf, Germany (Prof. Mario Siebler, MD, Holger Schade, MD, Torge Brosig, MD, Christina Boettcher, MD, and Verica Jovanovic, MD), 8; Department of Neurology, University Hospital of Münster, Germany (Prof. E. Bernd Ringelstein, MD, Martin Ritter, MD, and Ralf Dittrich, MD), 19; Faculty of Medicine, Vilnius University, and Vilnius University Santariskiu Klinikos Hospital, Lithuania (Dalius Jatuzis, MD), 19; Wagner-Jauregg Hospital, Linz (Prof. Franz Aichner, MD, and Stefan Guggenberger, MD), 1.

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Information & Authors

Information

Published In

Neurology®
Volume 77Number 8August 23, 2011
Pages: 751-758
PubMed: 21849657

Publication History

Received: January 6, 2011
Accepted: April 19, 2011
Published online: August 17, 2011
Published in print: August 23, 2011

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Disclosure

Dr. Topakian has received speaker honoraria from CSL Behring and funding for travel from sanofi-aventis. A. King reports no disclosures. Dr. Kwon has received research support from Otsuka Pharmaceutical Co., Ltd. and the Korea Health 21 Research and Development Project, Ministry of Health, Welfare and Family Affairs, Republic of Korea. Dr. Schaafsma and M. Shipley report no disclosures. Dr. Markus serves on scientific advisory boards for W. L. Gore & Associates, Inc., Boehringer Ingelheim, and Sanofi-Synthélabo; serves on the editorial boards of Stroke and Clinical Neurology and Neurosurgery; receives publishing royalties for Stroke Medicine (Oxford University Press, 2010); serves as a consultant for Archimex SAS and Shire plc; and has received research support from Archimex SAS, Shire plc, MRC UK, the Stroke Association, the European Union, and Wellcome Trust.

Authors

Affiliations & Disclosures

R. Topakian, MD
From Clinical Neuroscience (R.T., A.K., S.U.K., H.S.M.), St. Georges University of London, London, UK; Department of Neurology (R.T.), Academic Teaching Hospital Wagner-Jauregg, Linz, Austria; Department of Neurology (S.U.K.), Asan Medical Center, University of Ulsan, Seoul, Korea; Department of Clinical Neurophysiology (A.S.), Martini Ziekenhuis Groningen, the Netherlands; and Department of Epidemiology and Public Health (M.S.), University College London, London, UK.
A. King, BSc
From Clinical Neuroscience (R.T., A.K., S.U.K., H.S.M.), St. Georges University of London, London, UK; Department of Neurology (R.T.), Academic Teaching Hospital Wagner-Jauregg, Linz, Austria; Department of Neurology (S.U.K.), Asan Medical Center, University of Ulsan, Seoul, Korea; Department of Clinical Neurophysiology (A.S.), Martini Ziekenhuis Groningen, the Netherlands; and Department of Epidemiology and Public Health (M.S.), University College London, London, UK.
S.U. Kwon, MD, PhD
From Clinical Neuroscience (R.T., A.K., S.U.K., H.S.M.), St. Georges University of London, London, UK; Department of Neurology (R.T.), Academic Teaching Hospital Wagner-Jauregg, Linz, Austria; Department of Neurology (S.U.K.), Asan Medical Center, University of Ulsan, Seoul, Korea; Department of Clinical Neurophysiology (A.S.), Martini Ziekenhuis Groningen, the Netherlands; and Department of Epidemiology and Public Health (M.S.), University College London, London, UK.
A. Schaafsma, MD
From Clinical Neuroscience (R.T., A.K., S.U.K., H.S.M.), St. Georges University of London, London, UK; Department of Neurology (R.T.), Academic Teaching Hospital Wagner-Jauregg, Linz, Austria; Department of Neurology (S.U.K.), Asan Medical Center, University of Ulsan, Seoul, Korea; Department of Clinical Neurophysiology (A.S.), Martini Ziekenhuis Groningen, the Netherlands; and Department of Epidemiology and Public Health (M.S.), University College London, London, UK.
M. Shipley, MSc
From Clinical Neuroscience (R.T., A.K., S.U.K., H.S.M.), St. Georges University of London, London, UK; Department of Neurology (R.T.), Academic Teaching Hospital Wagner-Jauregg, Linz, Austria; Department of Neurology (S.U.K.), Asan Medical Center, University of Ulsan, Seoul, Korea; Department of Clinical Neurophysiology (A.S.), Martini Ziekenhuis Groningen, the Netherlands; and Department of Epidemiology and Public Health (M.S.), University College London, London, UK.
H.S. Markus, MD
From Clinical Neuroscience (R.T., A.K., S.U.K., H.S.M.), St. Georges University of London, London, UK; Department of Neurology (R.T.), Academic Teaching Hospital Wagner-Jauregg, Linz, Austria; Department of Neurology (S.U.K.), Asan Medical Center, University of Ulsan, Seoul, Korea; Department of Clinical Neurophysiology (A.S.), Martini Ziekenhuis Groningen, the Netherlands; and Department of Epidemiology and Public Health (M.S.), University College London, London, UK.
For the ACES Investigators
From Clinical Neuroscience (R.T., A.K., S.U.K., H.S.M.), St. Georges University of London, London, UK; Department of Neurology (R.T.), Academic Teaching Hospital Wagner-Jauregg, Linz, Austria; Department of Neurology (S.U.K.), Asan Medical Center, University of Ulsan, Seoul, Korea; Department of Clinical Neurophysiology (A.S.), Martini Ziekenhuis Groningen, the Netherlands; and Department of Epidemiology and Public Health (M.S.), University College London, London, UK.

Notes

Study funding: Supported by the British Heart Foundation Programme Grant RG99/073 and renewal RG04/002. The sponsor had no role in study design, data collection, data analysis, data interpretation, writing of the report, or in the decision to submit the paper for publication. H.S.M. had full access to all data in the study and had final responsibility for the decision to submit for publication.
Address correspondence and reprint requests to Dr. Raffi Topakian, Department of Neurology, Academic Teaching Hospital Wagner-Jauregg, Wagner-Jauregg-Weg 15, 4020 Linz, Austria [email protected]

Author Contributions

H.S.M. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: H.S.M. Acquisition of data: R.T., A.K., S.U.K., H.S.M. Analysis and interpretation of data: R.T., A.K., M.S., H.S.M. Drafting of the manuscript: R.T., H.S.M. Critical revision of the manuscript for important intellectual content: R.T., A.K., S.U.K., A.S., H.S.M. Statistical analysis: R.T., A.K., M.S. Obtained funding and supervised study: H.S.M.

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