Coronary Artery Disease and Atherosclerosis

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Despite advances in both treatment and prevention, complications of atherosclerotic disease remain the leading cause of morbidity and mortality in the Western World [56].More than 50% of atherosclerotic deaths can be attributed to coronary heart disease with estimated socioeconomic costs of $112 billion in the year 2002 in the United States alone. While atherosclerosis may progress slowly over years or decades, the occurrence of thrombosis as a consequence of sudden plaque rupture often leads to abrupt life threatening complications. Such acute events may explain why many people who die from coronary artery disease die suddenly without manifestation of typical symptoms. As reported by Glagov et al [3], the initial response to endothelial injury and initial development of atherosclerosis is outward remodeling of the artery, with relative preservation of lumen diameter. Such findings have been confirmed in living patients with invasive [57] and non-invasive techniques [58, 59]. Over 50% of all future myocardial infarctions occur in vascular regions with atherosclerotic thickening but non-critical luminal narrowing [60, 61]. This was confirmed in a prospective study of 4476 elderly subjects for whom carotid wall thickness, assessed non-invasively by high-resolution

B-mode ultrasound, was a stronger predictor of future stroke and myocardial infarction than were conventional coronary atherosclerotic risk factors [62]. The inference was that carotid wall thickening was a marker for diffuse atherosclerosis and thus correlated or predicted concomitant disease in the coronaries. The prognostic value of coronary wall thickness for predicting future events is probably very high. However, this has not yet been demonstrated because ultrasound evaluation of coronary wall thickness can only be performed invasively (intravascular ultrasound) and such studies are precluded in large, prospective, long-term endpoint trials. However, coronary wall disease, as indexed by coronary calcium, can be detected by rapid computed tomography (CT) and this approach has also been useful in predicting future cardiac events [63,64].The approach, however, does not directly measure wall thickness and cannot identify or characterize common, non-calcified atherosclerotic plaques. Conventional x-ray angiography is the current gold standard for the detection and treatment of intra-luminal (flow-limiting) coronary artery stenosis, but x-ray "luminography" provides minimal information on the magnitude of underlying atherosclerotic plaque burden. For these reasons, a non-invasive technique capable of measuring coronary wall thickness has great potential not only for the identification of disease at an early stage, but also for the prediction of future events and the evaluation of therapeutic strategies.

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