Coronary atherosclerosis and interventions: Pathological sequences and restenosis

The primary cause of cardiac morbidity and mortality in developed countries is ischemic (coronary) heart disease. The incidence of this disease is virtually all due to atherosclerosis, and ischemic heart disease is also the most prevalent disease in the industrialized world, causing over 40% of all deaths in the United States and Western Europe. In Japan, the incidence of ischemic heart disease due to coronary atherosclerosis is gradually increasing as well. Compared with the classical nomenclature of atherosclerosis; that is, fatty streak, fibrous plaque and complicated lesions, the term Stary's classification has been universally accepted because it reflects the more recently acquired knowledge about the morphological and biochemical details of the processes in coronary atherosclerosis, which have been obtained by new strategies such as angioscopy, intravascular ultrasound and molecular biological methods. The term Stary's classification has been applied for the coronary atherosclerosis of patients with acute coronary syndrome at the National Cardiovascular Center, for the analysis of predisposing atherosclerosis of these patients. The recent findings regarding acute coronary syndrome resulting from a rupture of coronary atherosclerotic plaques indicate that this syndrome is probably the most important mechanism underlying the sudden onset. It has been found that the risk of plaque rupture may depend more on plaque composition than on plaque size. Plaques rich in soft extracellular lipids and macrophages are possibly more vulnerable to plaque rupture. Two of the goals of the present review are to clarify how plaque disruption occurs and to elucidate the relationship between plaque disruption and coronary risk factors in elderly Japanese patients with acute coronary syndrome. Coronary stents have been shown to be efficacious in the treatment of acute and threatened closure complicating percutaneous transluminal coronary angioplasty (PTCA) and have produced encouraging initial results in the prevention of restenosis. In the autopsy study of restenosis after PTCA, it was observed that dense caps of collagen fibers in the adventitia in the vicinity of the disrupted internal elastic laminae were present in all of the remodeling lesions. It is suggested that remodeling, which resulted in adventitial scarring, is one of the major causative factors of restenosis after PTCA. The long-term success of stenting, however, remains limited by the occurrence of late in-stent restenosis, with an incidence of 20-42% depending on the stent design and the patient population studied. Another aim of the present review is to describe the pathological mechanism of restenosis after PTCA and/or stent replacement and, consequently, the vascular remodeling that occurs around adventitial tissue after PTCA and intimal hyperplasia that is chronically irritated by a foreign body granulomatous reaction after stenting. Finally, the results of the investigation of the effect of a tissue factor pathway inhibitor on the prevention of interventional restenosis is described.