The high-risk thin-cap fibroatheroma: a new kid on the block.

D espite continuous improvements in the catheter-based treatment of coronary artery disease (CAD), our field continues to struggle with the concept that percutaneous intervention may not prevent myocardial infarction or death in the stable patient. The main reason behind this controversial but rather accepted statement is that life-threatening coronary events arise most frequently from lesions that escape proper diagnosis and treatment. As a result, our efforts in clinical practice are almost totally consumed by the treatment of lesions that have limited impact on the natural history of atherothrombosis and CAD. Thus, it is imperative to reflect on this paradox, and do something about it. One way to start is to implement some of the knowledge we have acquired pertaining to our understanding of plaque rupture and thrombosis. We all agree that atherothrombosis evolves from nonobstructive CAD with specific plaque composition. 1–3 Atheroslcerotic lesions with increased lipid content can grow eccentrically to become very large plaques without obstructing the vessel lumen. These nonobstructive, positively remodeled, advanced plaques are completely silent on traditional stress testing and coronary angiography but portend an imminent risk for triggering acute events. Therefore, we can only make progress if we see beyond traditional testing and focus our attention on these high-risk lesions. The study of Lindsey et al 4 in this issue of Circulation: Cardio-vascular Interventions represents a step forward in the right direction by identifying an increased incidence of thin-cap fibroatheroma (TCFA) in patients with long-standing diabetes mellitus. Early in atherogenesis, the nascent fatty streak evolves into a transitional lesion, also known as the preatheroma. Death of macrophages, hypoxia, extravasation of erythrocytes, and free cholesterol replace lipid pools to form necrotic cores. Disease progresses through necrotic core expansion by active digestion of collagen, reducing the rim of fibrous tissue separating the core from the lumen. This advanced lesion is the hallmark of human atherosclerosis, and the American Heart Association termed it the fibroatheroma. When macro-phage-derived collagenolytic activity ruptures the cap of the fibroatheroma, the highly thrombogenic core is exposed to circulating blood and triggers thrombosis. 5 In fact, when quantified by ocular micrometry, all ruptured plaques are characterized by a thin fibrous cap, (Ͻ65 ␮m in thickness), a large necrotic core, and increased macrophage infiltration. 6 Adding these 3 characteristics to the American Heart Association definition of fibroatheroma led to the distinction of TCFA as a separate entity. 6 Most importantly, the pivotal concept that plaque …