Published online before print November 1, 2007, doi: 10.1161/STROKEAHA.107.496851
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(Stroke. 2007;38:e158.)
© 2007 American Heart Association, Inc.
Letters to the Editor |
Response to Letter by Tang et al
The Vascular Biology Unit, James Cook University, Townsville, Queensland, Australia
Response:
Altaf and colleagues report the association of intraplaque hemorrhage identified on MRI and ipsilateral cerebral events during a mean follow-up of 34 days in 66 patients presenting with amaurosis fugax, TIA or stroke awaiting carotid endarterectomy.1 This publication raises a number of issues some of which are discussed in the letter by Tang and colleagues.2 How reliably is intraplaque hemorrhage associated with carotid embolization and symptom development? A systematic review in 2000 identified 7 histology studies comparing atheroma removed from symptomatic and asymptomatic patients.3 All were small studies (largest 99, total 360 patients) and demonstrated no association between histology defined intraplaque hemorrhage and symptoms.3 The principal finding of the systematic review was the association of both fibrous cap rupture and inflammation with symptoms.3 Recently, Redgrave and colleagues in a study of 526 endarterectomy specimens removed from symptomatic patients reported an increased incidence of intraplaque hemorrhage (OR, 3; 95% CI, 1.6 to 5.5) in atheroma with cap rupture.4 The authors demonstrated a strong negative association between cap rupture and inflammation but not intraplaque hemorrhage and time since stroke.4 Because the risk of recurrent stroke in patients with symptomatic carotid stenosis decreases with time since symptoms, these findings could be interpreted as confirming the relevance of cap rupture and inflammation but not intraplaque hemorrhage to cerebral thromboembolism. Importantly, this study also demonstrated the marked heterogeneity in mechanisms likely involved in cerebral embolization with marked interpatient variation and differing findings for patients presenting with TIA and stroke.4 The determinants of outcome after stroke or TIA related to carotid stenosis have been defined with some precision. This makes it possible to select patients with symptomatic carotid stenosis who benefit markedly from carotid endarterectomy based on clinical risk factors and simple imaging findings.5,6 It therefore appears unlikely that the use of MRI will come to have an important role in management of patients with symptomatic tight carotid stenosis, as examined in the study of Altaf et al.1 The clinical need is to identify patients yet to experience focal neurological symptoms who will develop stroke without warning. Local plaque-related features suggesting plaque rupture, inflammation or thromboembolism identified on ultrasound, transcranial Doppler, CT, MRI and scintigraphic imaging, plus systematic markers identified in serum or plasma have all been related to stroke risk in some studies.7–11 Multicenter prospective studies of patients with asymptomatic carotid stenosis have not as yet consistently identified imaging or blood findings which can be used in clinical practice to identify patients most likely to benefit from carotid intervention. The recent Asymptomatic Carotid Surgery Trial, for example, did not find an association between plaque echoluscency identified on ultrasound and subsequent stroke.12 Important obstacles to this type of research include the prolonged and repeat imaging that may be required and the need for extended follow-up of large groups of patients who are often selected for interventions. It is possible that inflammation and plaque rupture, the most consistent histology features associated with unstable plaque, may be transient events at the time (or even after) thromboembolism, making it impossible to use imaging of atheroma to identify high-risk atherosclerosis. The goal of identifying patients with higher than average stroke risk associated with their asymptomatic carotid stenosis remains an important clinical need giving the ongoing concern that the very low stroke-mortality rates after carotid endarterectomy reported in ACST and ACAS are not being reproduced in general practice.12,13 These concerns are emphasized by the recent publication of a number of carotid trials in which stroke-mortality rates have been frequently higher than reported in earlier studies comparing endarterectomy and medical therapy.14–16 Although the efforts of Altaf and colleagues to better understand the mechanisms underlying recurrent stroke in patients with tight carotid atherosclerosis is interesting, the main issue in the management of these patients is the need to reduce the delay for carotid surgery, thereby minimizing the risk of stroke while awaiting intervention.17 The important aim of identifying high-risk plaque in asymptomatic patients in routine clinical practice presently remains unresolved.
Acknowledgments
Disclosures
None.
References
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2. Tang TY, Howarth SP, Walsh SR, Gaunt ME, Gillard J. Contralateral carotid intraplaque hemorrhage may reduce the predictive value of fat-suppressed T1-weighted MRI in symptomatic carotid disease. Stroke. 2007; 38: e156–e157.
3. Golledge J, Greenhalgh RM, Davies AH. The symptomatic carotid plaque. Stroke. 2000; 31: 774–781.
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13. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995; 273: 1421–1428.
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15. Mas JL, Chatellier G, Beyssen B, Branchereau A, Moulin T, Becquemin JP, Larrue V, Lievre M, Leys D, Bonneville JF, Watelet J, Pruvo JP, Albucher JF, Viguier A, Piquet P, Garnier P, Viader F, Touze E, Giroud M, Hosseini H, Pillet JC, Favrole P, Neau JP, Ducrocq X. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med. 2006; 355: 1660–1671.
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17. Fairhead JF, Mehta Z, Rothwell PM. Population-based study of delays in carotid imaging and surgery and the risk of recurrent stroke. Neurology. 2005; 65: 371–375.
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