Rapid coronary artery disease progression and angiographic stenosis morphology

It is established that the progression of coronary artery disease is neither linear nor predictable. The unpredictable and often episodic nature of coronary disease progression can be explained by rapid increase of stenosis severity due to thrombosis, which occurs as a complication of the atherogenic process. Rapid coronary stenosis progression is most often responsible for the acute clinical manifestations of coronary artery disease, i.e. sudden cardiac death, acute myocardial infarction and unstable coronary syndromes. Recently, it has been shown that stenosis progression, whether clinically "silent" or associated with acute coronary events, is a strong predictor of cardiovascular risk. Atheromatous plaques associated with rapid coronary artery disease progression have well defined anatomo-pathological characteristics and are usually termed "vulnerable" or "unstable", terms which indicate both their propensity to acute disruption and increased thrombogenicity that may lead to the development of acute coronary events. Plaques have been regarded, in the past, as being inert and staying almost unchanged for years. However, they are very active entities. The fibrous cap is in a balance between smooth muscle cells producing collagen and the macrophages degrading collagen. The thickness of the cap depends on the relative activity of those two components and there is, therefore, a danger of the fibrous cap rupturing. Although only a relatively small proportion of all coronary artery lesions in patients with angina pectoris undergo complications that lead to fibrous cap disruption and acute coronary events, these stenoses are responsible for the majority of cases of serious coronary events. Thus the identification of vulnerable plaques that may lead to increased risk of coronary events will most certainly help in the rational management of patients with coronary artery disease. Angiographic studies have indicated that "complex" lesion morphology is associated with increased risk of myocardial infarction and "ulcerated" plaques identify vulnerable lesions. We therefore reasoned that the identification of angiographically complex coronary stenoses could provide a valuable marker of cardiovascular risk in relation to rapid disease progression. Our group sought to investigate the role of angiographically complex lesions as a marker of rapid disease progression in different clinical settings. We took advantage of the fact that patients with stable angina pectoris requiring routine myocardial revascularisation in our institution are put on waiting lists. We observed that complex lesions progressed more than smooth stenoses of similar severity both in patients presenting with stable angina and in patients presenting with unstable angina. Why complex plaques should be particularly vulnerable to rapid stenosis progression is speculative. In this paper we discuss the possible mechanisms that may explain an association between complex stenosis and acute coronary events.