ArticlesEvidence of a chronic systemic cause of instability of atherosclerotic plaques
Introduction
The development of atherosclerosis is a chronic process that is caused, or at least accelerated, in part by hypertension, cigarette smoking, diabetes, and hyperlipidaemia.1 However, the risks of the major thrombotic and thromboembolic complications of atherosclerosis appear to be related more to the stability of atheromatous plaques than to the extent of disease. Stable angina is associated with smooth fibrous coronary-artery plaques, whereas unstable angina, acute myocardial infarction, and sudden cardiac death are almost invariably associated with irregular or ruptured plaques.2, 3, 4 Similarly, in patients with carotid-artery atherosclerotic disease, plaque irregularity and rupture are closely associated with the occurrence of cerebral ischaemic events,5, 6 and patients with irregular or ulcerated plaques on carotid angiography have a higher risk of ischaemic stroke irrespective of the degree of stenosis of the vessel lumen.7, 8
The factors that influence the stability of plaques are uncertain. Local factors, such as sheer stress or vessel and plaque anatomy, are important,9 but there is evidence that systemic factors may also be involved. Plaque instability is associted with inflammation and haemorrhage within plaques,10, 11 and there is evidence that these processes may be induced by autoimmunity and infection.12, 14 If plaque stability is influenced by systemic factors—infection, autoimmunity, or genes—and these factors are present in just a proportion of individuals, some individuals with atherosclerotic vascular disease will be more prone to instability and rupture of plaques, and so clinical complications, than others. Unstable plaques would be present at multiple sites in certain individuals more frequently than would be expected by chance alone. To test this hypothesis, we studied plaque-surface morphology on 5393 carotid bifurcation angiograms from 3007 patients with a symptomatic carotid stenosis in the European carotid surgery trial.15 We assessed the extent to which plaque-surface irregularity at one site, the symptomatic carotid artery, was associated with irregularity at a distant site, the contralateral carotid artery, and the extent to which plaque irregularity at these sites was associated with previous myocardial infarction and subsequent myocardial infarction and non-stroke vascular death (due mainly to coronary-artery disease).
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Patients
We studied the carotid angiograms of patients randomly allocated treatment in the European Carotid Surgery Trial (ECST), the methods and results of which have been published previously.15 Briefly, patients with ocular or carotid-territory cerebral ischaemia, and who had evidence of carotid bifurcation stenosis on an angiogram, were randomly assigned carotid endarterectomy and best medical treatment or best medical treatment alone. Baseline clinical data were recorded and patients were followed
Results
There were no differences in baseline clinical characteristics between patients in whom a contralateral carotid angiogram was available for study (2386) and those in whom it was not (621). The mean degree of carotid stenosis of the arteries studied was 58·4% (SD 20·8) for the symptomatic artery and 46·7% (17·4) for the contralateral artery. There was a weak correlation between the degree of stenosis on the two sides (r=0·2, p < 0·001). Observers A and B agreed on the classification of
Discussion
We have shown that patients with angiographic plaque-surface irregularity in one carotid artery are more likely than would be expected by chance to have irregular plaques in the other carotid artery. These patients are more likely than patients with smooth plaques to have had a previous myocardial infarction and are more likely to die as a consequence of a subsequent acute myocardial infarction or other non-stroke vascular disorders, and to have sudden cardiac deaths. Since acute myocardial
References (22)
- et al.
Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques
Lancet
(1989) - et al.
Infection, inflammation, and infarction: does acute endothelial dysfunction provide a link?
Lancet
(1997) - et al.
Measurement of carotid stenosis and assessment of plaque surface morphology: do angiographic technique or image quality matter?
Clin Radiol
(1998) - et al.
A reappraisal of the kappa coefficient
J Clin Epidemiol
(1988) Atherosclerosis
- et al.
The pathogenesis of coronary artery disease and the acute coronary syndromes
N Engl J Med
(1992) - et al.
Coronary atherectomy. Clinical, angiographic and histological findings and observations regarding potential mechanisms
Circulation
(1990) - et al.
Plaque fisuring-the cause of acute myocardial infarction. Sudden ischaemic death, and crescendo angina
Br Heart J
(1985) - et al.
Recently occluded intracranial and extracranial carotid arteries: relevance of unstable atherosclerotic plaque
Stroke
(1999) - et al.
Plaque ulceration and lumen thrombus are the main sources of cerebral microemboli in high-grade internal carotid artery stenosis
Stroke
(1995)
Significance of plaque ulceration in symptomatic patients with high-grade carotid stenosis
Stroke
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