It is well established that coronary atherosclerosis is by far the most common cause of acute myocardial ischemia, with thrombosis as the trigger for myocardial infarction. Less common causes of myocardial ischemia include coronary artery dissection, coronary arteritis, coronary artery vaso-spasm, emboli, and rarely myocardial bridging. Until recently, the majority of our understanding of the mechanisms of conversion from chronic to acute coronary artery disease had largely been limited to postmortem data. In 1912, Dr. James Herrick published an autopsy study that associated the clinical presentation of acute infarction with a thrombotic coronary occlusion.3 Coronary artery occlusion resulting in acute coronary syndrome occurs by three mechanisms: thrombosis, plaque erosion, or plaque rupture. Plaque morphology described angiographically or via intravascular ultrasound or angioscopy has been instrumental in identifying atherosclerotic plaques that were more likely to cause acute coronary syndrome, the so-called vulnerable plaque. However, our understanding of the cellular and molecular mechanisms of how a vulnerable plaque develops is far from being complete.
Histopathologic and angioscopic studies have demonstrated that both plaque rupture and erosion leading to thrombosis are the most common causes of acute coronary syndrome. Plaques that are more likely to rupture are termed vulnerable plaques or thin-cap fibroatheromas. They are characterized as being eccentric, with a larger lipid core, fewer smooth muscle cells, and a greater number of macrophages.4, 5, 6 Plaque with a lipid core often contains oxidized lipids and macrophage-derived tissue factor, which makes the plaque highly thrombogenic when its contents are exposed to blood. This in turn activates the clotting cascade, as well as platelet adhesion, activation, and aggregation.7 It is thought that plaque rupture accounts for > 70% of fatal acute myocardial infarctions and/or sudden cardiac death. The smaller concentration of smooth muscle cells is thought to weaken the mechanical resistance of the plaque. Plaque rupture generally occurs where the plaque is thinnest and has the highest degree of inflammatory cells (ie, foam cells). In an eccentric plaque this typically occurs at the shoulder region, which is the junction between the plaque and the area of the vessel wall that is less diseased.8
Plaque erosion refers to a thin-cap fibroatheroma that literally develops a fissure or defect in the fibrous cap, thereby exposing the thrombogenic core to flowing blood.9 Erosions occur over plaques that are rich in smooth muscle cells and proteoglycans. Luminal thrombi occur in denuded areas lacking surface endothelium. Unlike plaques prone to rupture, plaques prone to erosion typically lack a necrotic core of lipid but rather are composed of macrophages and lymphocytes. Lastly, calcified nodules are plaques with luminal thrombi showing calcified nodules protruding into the lumen through a disrupted thin fibrous cap. There is absence of endothelium at the site of the thrombus as well as lack of inflammatory cells (macrophages and T lymphocytes). There is little or no necrotic core and typically there is no obvious rupture of the lesion. However, there are superficial, dense, calcified nodules within the intima, which appear to be erupting through fibrous tissue into the lumen, possibly causing the thrombus.10
Numerous postmortem studies have identified ruptured plaque as the cause of thrombosis in acute myocardial infarction. Richardson et al studied 85 coronary thrombi postmortem and found a disrupted atheromatous plaque beneath 71 (84%) of the thrombi.11 Studies comparing coronary angiograms before and after the onset of the acute coronary syndrome confirmed that the majority of culprit lesions demonstrate a luminal stenosis of < 70% on the initial angiogram. However, the lesions with a less severe degree of luminal stenosis (< 50%) on the initial angiogram were more likely to be the cause of acute coronary syndrome.12, 13, 14, 15,16 The composition and vulnerability of plaque rather than its volume or the consequent severity of stenosis produced have emerged as being the most important determinants of the development of the thrombus-mediated acute coronary syndromes.8 In addition, both angiographic studies and intravascular ultrasound of plaque morphology in patients presenting with acute coronary syndrome have shown that multiple complex or ruptured plaques exist simultaneously. This implies a systemic process in the pathogenesis of plaque rupture.17 The relationship between systemic markers of inflammation and the acute coronary syndromes is beyond the scope of this chapter.18
The clinical presentation and outcome depend on the location, severity, and duration of myocardial ischemia. Unstable angina and NSTEMI are typically caused by partial coronary artery obstruction by a thrombus, while STEMI is caused by complete coronary artery obstruction. The clinical presentation can, of course, be mediated by other factors such as vascular tone or the presence of collaterals.19 It is noteworthy that many coronary arteries apparently occlude silently without causing myocardial infarction, probably because of a well-developed collateral circulation at the time of occlusion.20 Morphological studies suggest that plaque progression beyond 40% to 50% cross-sectional luminal narrowing may occur secondary to repeated asymptomatic plaque ruptures, which may lead to healing with infiltration of smooth muscle cells.7, 18