I nvestigators, working in the field of identification and treatment of high-risk/vulnerable atherosclerotic plaques and patients, have recognized that an increased understanding of the pathophysiology of coronary thrombosis and onset of acute coronary syndromes has created the need for agreement on nomenclature [ 1], This chapter gives a summary of that agreement.
The terms in figure 1 are proposed for use on a conceptual basis. The progression from asymptomatic atherosclerosis, to a high-risk/vulnerable plaque, to a thrombosed plaque, and to clinical events is presented. It is of note that the later stages of the progression may be repeated in a relatively short time interval as documented by the high short-term risk of a recurrent event in patients with acute coronary syndromes. This may be caused by rethrombosis of the lesion causing the index event, and/or the simultaneous occurrence of multiple high-risk/vulnerable plaques and/or thrombosed plaques that have not previously caused symptoms. An acute coronary syndrome may be a clinical marker of widespread (multifocal) disease activity in the coronary arteries, possibly related to inflammation [2-9].
The primary clinical and preventive goal is to identify patients who are vulnerable to acute coronary thrombosis. Such patients are likely to have a high atherosclerotic burden, high-risk/vulnerable plaques, and/or thrombo-genic blood . There is an important need to improve diagnostic methods to identify vulnerable patients, and the plaques, which contribute to their increased risk.
Studies indicate that there are plaques at increased risk of thrombosis and rapid stenosis progression, which often lead to symptomatic disease. Synonyms to be used for such plaques are 'vulnerable', 'high-risk', or 'thrombosis-prone' plaques.
At the present time, there is no widely accepted diagnostic method to prospectively identify these plaques. Until such information is provided, the suggested synonyms should only be used to describe the concept and function of these plaques, and not their histologic basis.
Histologic Features of Plaques Causing Coronary Artery Thrombosis
At present, the most detailed evidence concerning the plaques causing coronary thrombosis and rapid lesion progression, or symptomatic disease, is derived from autopsy studies [10-14].
In the acute coronary syndromes, the lesion causing most clinical events is often a plaque complicated by thrombosis extending into the lumen [12-15]. Such plaques are termed 'thrombosed plaques'. In some cases, multiple throm-bosed plaques may exist, only one of which is acting as the culprit lesion. A plaque may also develop thrombosis, which remains asymptomatic due to the presence of collaterals, or failure of the thrombus to significantly impede blood
Fig. 2. Various types of plaque. A Ruptured plaque with thrombosis: a cross section of a coronary artery is cut just distal to a bifurcation. The atherosclerotic plaque to the left (circumflex branch) is fibrotic and partly calcified whereas the plaque to the right (marginal branch) is lipid-rich with a non-occluding thrombus superimposed. B, C Eroded
Fig. 2. Various types of plaque. A Ruptured plaque with thrombosis: a cross section of a coronary artery is cut just distal to a bifurcation. The atherosclerotic plaque to the left (circumflex branch) is fibrotic and partly calcified whereas the plaque to the right (marginal branch) is lipid-rich with a non-occluding thrombus superimposed. B, C Eroded flow. However, such subclinical thrombosis may contribute to the rapid progression of stenosis [16, 17]. In cases of stable angina, the culprit lesion is often a non-thrombosed plaque.
The following terms are proposed to describe the thrombosed plaques causing the coronary syndromes: A ruptured plaque' - a plaque with deep injury with a real defect or gap in the fibrous cap that had separated its lipid-rich atheromatous core from the flowing blood, thereby exposing the thrombo-genic core of the plaque (fig. 2A). This is the most common cause of coronary thrombosis [11-13]. 'An eroded plaque' - a plaque with loss and/or dysfunction of the lumenal endothelial cells leading to thrombosis (fig. 2B, C). There is no structural defect (beyond endothelial injury) or gap in the plaque, which is often rich in smooth muscle cells and proteoglycans . A plaque with a calcified nodule' - a heavily calcified plaque with the loss and/or dysfunction of endothelial cells over a calcified nodule (fig. 2D). This is the least common of the three causes of thrombosis described here .
There is considerable interest in the identification of plaques prior to the occurrence of thrombosis. On the basis of knowledge of the types of plaques identified as causes of thrombosis (ruptured, eroded and calcific nodule plaques), the following types of plaques are suspected to be vulnerable plaques.
Retrospective pathologic studies of plaque rupture with thrombosis suggest that prior to the event, the plaque was an inflamed, thin-cap fibroathero-ma (TCFA) (fig. 2E) [11-14, 18-20]. The major components of such TCFA are:
plaques with thrombosis: plaque erosion lesions from two different patients showing in B a lesion with lipid pool (Lp) and in C a necrotic core (Nc) with luminal thrombi (Th). Note a thick fibrous cap above the necrotic core in C and a lack of communication between it and the lumen. D Calcified nodule: a section of the mid right coronary artery shows an eccentric lesion with extensive calcification (calcified plate) and surface calcified nodules with loss of fibrous cap and luminal fibrin deposition. E Inflamed thin-cap fibroathero-ma: a section of a coronary artery contains a large lipid-rich core that is covered by a thin fibrous cap (arrowheads). The lumen contains contrast medium injected postmortem. The fibrous cap is severely inflamed, containing many macrophage foam cells (asterisk), and extravasated erythrocytes within the necrotic and avascular core just beneath the cap, indicating that the cap is ruptured nearby.
(a) a lipid-rich, atheromatous core; (b) a thin fibrous cap, with (i) macrophage and lymphocyte infiltration and/or (ii) decreased smooth muscle cell content, and (c) expansive remodeling.
Retrospective pathologic studies of plaque erosion with thrombosis suggest that, prior to the event, the plaque was often rich in proteoglycans, but, in most cases, lacked a distinguishing structure such as a lipid pool or necrotic core. If a lipid-rich core is present, the fibrous cap is usually thick and rich in smooth muscle cells . These plaques are often associated with constrictive remodeling.
Retrospective pathologic studies of plaques with thrombosis covering a calcified nodule suggest that, prior to the event, the plaque appeared to be heavily calcified with a calcified nodule protruding into the lumen .
While such plaques (an inflamed TCFA, a proteoglycan-rich plaque, and a plaque with a calcified nodule) are suspected to be vulnerable plaques, they cannot be designated as such until prospective studies provide the necessary supporting data. Hence, an inflamed TCFA is best described as a 'suspected' vulnerable plaque, since, while confirmatory data are lacking, its structure definitely resembles that of ruptured plaques.
Novel Imaging Techniques Will Provide Additional Information on
New technologies to improve characterization of plaque in patients are under development [19-29]; These techniques seek to identify the histologic features, discussed above, of plaques suspected to represent vulnerability, and provide additional information about plaques that has not heretofore been available (data on structure, composition, deformability, pathophysiology, metabolism, temperature, etc.). The novel information will expand the list of features suspected to represent vulnerability. These features need validation in longitudinal, prospective, clinical trials that will document the natural history of plaques. Once such trials are positive, it may then be possible to identify a vulnerable plaque prospectively in an individual patient.
Finally, it is the hope that widespread adoption of the terminology established in Schaar et al. , and briefly summarized in this chapter, will accelerate progress in the prevention of acute coronary events.
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