Molecular Markers, Fibrous Cap Rupture, and the Vulnerable Plaque

he study by Faber et al 1 in this issue of Circulation Research uses subtraction suppression hybridization (SSH) to identify genes specific to the ruptured atherosclerotic plaque.This article may represent the early days in the oncoming studies of advanced atherosclerosis, a surprisingly neglected area of study.Part of the reason for this neglect has been the confusion in the past several years over the term "vulnerable plaques"lesions of atherosclerosis that are thought to be associated with a higher risk for thromboembolic complications.The American Heart Association (AHA), unfortunately, has encouraged the application of this term to a specific morphology.2 The problem is that the AHA classifications scheme implies that we can define critical early and "vulnerable" lesions based on morphology observed at autopsy.Virmani et al 3 have offered a simpler, less dogmatic scheme that uses morphological terms without implying mechanism.As that article discusses, a purely descriptive, nonjudgmental approach leads to more focused questions about the specific processes and related morphologies that could be hypotheses for further study.Testing those hypotheses, as we will discuss, may now be possible depending on very new methods that permit noninvasive imaging of the evolving lesions.Faber et al, 1 although using the AHA scheme, do a very good job of specifying the morphology of their lesions.In essence, the ruptured lesions they describe have thin fibrous caps, multiple areas of disruption of that cap, and evidence of acute rupture leading to thrombosis.Lesions with similar characteristics, lacking frank rupture, are the sort called types V and VI by the AHA criteria and asserted to be "vulnerable".2 Unfortunately, autopsy data cannot determine whether such lesions are prodromal, causative, or merely coincidentally associated with the clinical events leading to death from coronary artery occlusion.Arbustini et al, 4 for example, found a high incidence of such lesions even in patients with advanced atherosclerosis dying of unrelated causes.Moreover, at least a portion of patients, especially among younger women, appear to die of occlusive thrombosis without any of The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.