Background: Rupture of atherosclerotic plaque is the main cause of acute coronary syndromes and carotid territory ischaemic stroke. Haemodynamic stress is important in early plaque formation and may affect the stability of mature plaques. There is some evidence that macrophage infiltration and plaque rupture tend to localise to the proximal (upstream) part of the plaque where shear stress is highest. However, previous studies have been too small to assess this reliably. We studied the site of ulceration in a large number of carotid plaques. Methods: We studied angiograms of 3,007 symptomatic carotid stenoses, and the pathological appearance of 119 carotid plaques (77 asymptomatic), to identify the presence and position of plaque ulceration. Results: Angiographic ulceration, which was present in 421 patients (14%), was more likely to be proximal than distal to the point of maximum stenosis (OR = 16.6, 95% CI = 11.6–26.9, p < 0.001). This trend increased with severity of stenosis (p = 0.002). Pathological examination of the 119 carotid plaques also showed that ulceration was more likely to occur proximal to the point of maximum stenosis (OR = 6.1, 95% CI = 2.8–13.6, p < 0.001). Conclusions: Ulceration of carotid plaques, visible on angiography or on pathological examination, is seen most often in the proximal (upstream) part where shear stress is highest.

1.
Davies MJ, Thomas AC: Plaque fissuring – The cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 1985;53:363–373.
2.
Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes. Part 1. N Engl J Med 1992;326:242–250.
3.
Lammie GA, Sandercock PA, Dennis MS: Recently occluded intracranial and extracranial carotid arteries: Relevance of the unstable atherosclerotic plaque. Stroke 1999;30:1319–1325.
4.
Golledge J, Greenhalgh RM, Davies AH: The symptomatic carotid plaque. Stroke 2000;31:774–781.
5.
Rothwell PM, Gibson R, Warlow CP: Interrelation between plaque surface morphology and degree of stenosis on carotid angiograms and the risk of ischemic stroke in patients with symptomatic carotid stenosis. Stroke 2000;31:615–621.
6.
Rothwell PM, Villagra R, Gibson R, Donders RC, Warlow CP: Evidence of a chronic systemic cause of instability of atherosclerotic plaques. Lancet 2000;355:19–24.
7.
Estol C, Claasen D, Hirsch W, Wechsler L, Moossy J: Correlative angiographic and pathologic findings in the diagnosis of ulcerated plaques in the carotid artery. Arch Neurol 1991;48:692–694.
8.
O’Donnell TF Jr, Erdoes L, Mackey WC, McCullough J, Shepard A, Heggerick P, et al: Correlation of B-mode ultrasound imaging and arteriography with pathologic findings at carotid endarterectomy. Arch Surg 1985;120:443–449.
9.
Comerota AJ, Katz ML, White JV, Grosh JD: The preoperative diagnosis of the ulcerated carotid atheroma. J Vasc Surg 1990;11:505–510.
10.
Blaisdell FW, Glickman M, Trunkey DD: Proceedings: Ulcerated atheroma of the carotid artery. Arch Surg 1974;108:491–496.
11.
Eliasziw M, Streifler JY, Fox AJ, Hachinski VC, Ferguson GG, Barnett HJ: Significance of plaque ulceration in symptomatic patients with high-grade carotid stenosis: North American Symptomatic Carotid Endarterectomy Trial. Stroke 1994;25:304–308.
12.
Ku DN, Giddens DP, Zarins CK, Glagov S: Pulsatile flow and atherosclerosis in the human carotid bifurcation: Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis 1985;5:293–302.
13.
Zarins CK, Giddens DP, Bharadvaj BK, Sottiurai VS, Mabon RF, Glagov S: Carotid bifurcation atherosclerosis: Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ Res 1983;53:502–514.
14.
Motomiya M, Karino T: Flow patterns in the human carotid artery bifurcation. Stroke 1984;15:50–56.
15.
Traub O, Bradford CB: Laminar shear stress: Mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol 1998;18:677–685.
16.
Glagov S, Zarins C, Giddens DP, Ku DN: Hemodynamics and atherosclerosis: Insights and perspectives gained from studies of human arteries. Arch Pathol Lab Med 1988;112:1018–1031.
17.
Meairs S, Hennerici M: Four-dimensional ultrasonographic characterization of plaque surface motion in patients with symptomatic and asymptomatic carotid artery stenosis. Stroke 1999;30:1807–1813.
18.
Walpola PL, Gotlieb AI, Cybulsky MI, Langille BL: Expression of ICAM-1 and VCAM-1 and monocyte adherence in arteries exposed to altered shear stress. Arterioscler Thromb Vasc Biol 1995;15:2–10.
19.
Nagel T, Resnick N, Atkinson WJ, Dewey CF Jr, Gimbrone MA Jr: Shear stress selectively upregulates intercellular adhesion molecule 1 expression in cultured human vascular endothelial cells. J Clin Invest 1994;94:885–891.
20.
Resnick N, Collins T, Atkinson W, Bonthron DT, Dewey CF Jr, Gimbrone MA Jr: Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element. Proc Natl Acad Sci USA 1993;90:4591–4595.
21.
Seigel JM, Markou CP, Ku DN, Hanson SR: A scaling law for wall shear rate through an arterial stenosis. J Biomech Eng 1994;116:446–451.
22.
Dirksen MT, van der Wal AC, van den Berg FM, van der Loos CM, Becker AE: Distribution of inflammatory cells in atherosclerotic plaques relates to the direction of flow. Circulation 1998;98:2000–2003.
23.
Levesque MJ, Liepsch D, Moravec S, Nerem RM: Correlation of endothelial cell shape and wall shear stress in a stenosed dog aorta. Arteriosclerosis 1986;6:220–229.
24.
Stroud JS, Berger SA, Saloner D: Numerical analysis of flow through a severely stenotic carotid artery bifurcation. J Biomech Eng 2002;124:9–20.
25.
Tricot O, Mallat Z, Heymes C, Belmin J, Leseche G, Tedgui A: Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques. Circulation 2000;101:2450–2453.
26.
Binns RL, Ku DN: Effect of stenosis on wall motion: A possible mechanism of stroke and transient ischaemic attack. Arteriosclerosis 1989;9:842–847.
27.
Masawa N, Yoshida Y, Yamada T, Joshita T, Sato S, Mihara B: Three-dimensional analysis of human carotid atherosclerotic ulcer associated with recent thrombotic occlusion. Pathol Int 1994;44:745–752.
28.
Svindland A, Torvik A: Atherosclerotic carotid disease in asymptomatic individuals: A histological study of 53 cases. Acta Neurol Scand 1988;78:506–517.
29.
European Carotid Surgery Trialists’ Collaborative Group: Randomised trial of endarterectomy for recently symptomatic carotid stenosis: Final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379–1387.
30.
Rothwell PM, Gibson RJ, Slattery J, Warlow CP: Prognostic value and reproducibility of measurements of carotid stenosis: A comparison of three methods on 1,001 angiograms. Stroke 1994;25:2440–2444.
31.
Rothwell PM, Gibson RJ, Slattery J, Sellar RJ, Warlow CP: Equivalence of measurements of carotid stenosis: A comparison of three methods on 1,001 angiograms. Stroke 1994;25:2435–2439.
32.
Easton DF, Peto J, Babiker AG: Floating absolute risk: An alternative to relative risk in survival and case-control analysis avoiding an arbitrary reference group. Stat Med 1991;10:1025–1035.
33.
Bakker SJ, Gans RO: About the role of shear stress in atherogenesis. Cardiovasc Res 2000;45:270–272.
34.
Cheng GC, Loree HM, Kamm RD, Fishbein MC, Lee RT: Distribution of circumferential stress in ruptured and stable atherosclerotic lesions: A structural analysis with histopathological correlation. Circulation 1993;87:1179–1187.
35.
Richardson PD, Davies MJ, Born GV: Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 1989;ii:941–944.
36.
Streifler JY, Eliasziw M, Fox AJ, Benavente OR, Hachinski VC, Ferguson GG, Barnett HJ: Angiographic detection of carotid plaque ulceration: Comparison with surgical observations in a multicenter study. Stroke 1994;25:1130–1132.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.