ABSTRACT
Atherosclerosis, with its complications, continues to be the leading cause of mortality and morbidity throughout the developed world. Its consequences are also beginning to be felt in less well-developed regions of the globe.1 It has until recently been thought of as a degenerative disease, affecting predominantly older people, chronically progressing over many years, and eventually leading to symptoms through mechanical effects on bloodflow. Because of the perceived insidious and relentless nature of its development, there has been a somewhat pessimistic view of the potential to modify its progression by medical therapy. Management has instead been dominated by interventional revascularization approaches, targeting the largest and most visible or symptomatic lesions with angioplasty or bypass surgery. There has been little emphasis on pre-symptomatic disease evaluation or the treatment of high-risk asymptomatic patients. Recently, this defeatist view of the pathogenesis and progression of atherosclerosis has begun to change: first, because careful descriptive studies of the underlying pathology of atherosclerosis have revealed that atherosclerotic plaques differ in their cellular composition, and that the cell types predominating in the plaque can determine the risk of a fatal clinical event such as myocardial infarction or stroke; second, because cellular and molecular biological studies, particularly involving transgenic mice, have emphasized the importance of inflammatory cells and inflammatory mediators in the pathogenesis of atherosclerosis; and third, and most importantly, because several large-scale clinical studies have shown that several statin drugs are able to reduce clinical events in patients with established atherosclerosis without necessarily reducing the size of flow-limiting lesions. Taken together, this evidence has shown that, rather than being an irreversible progressive disease, atherosclerosis is a dynamic, inflammatory process that is amenable to medical therapy. Understanding the cellular and molecular interactions that determine the development and progression of
atherosclerosis brings with it opportunities to develop novel therapeutic agents targeting key molecular and cellular interactions in its aetiology. In addition, the recognition that the clinical consequences of atherosclerosis depend almost entirely on plaque composition also argues for a new approach to diagnosis dominated less by determining lumen narrowing, as in angiography, but focused more on plaque cellular content and activation.
