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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 3007 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., (Copyright 2003 S. Karger AG, Basel)