Chapter 53

The formation of an acute thrombus on a ruptured coronary atherosclerotic lesion, obstructing coronary blood flow and reducing the oxygen supply to the myocardium, leads to the onset of acute coronary syndromes (ACS). These thrombotic episodes largely occur in response to atherosclerotic lesions that have progressed to a high-risk inflammatory or prothrombotic stage. Although they are distinct from one another, the atherosclerotic and thrombotic processes appear to be closely interrelated, causing ACS through a complex, multifactorial process called atherothrombosis. ACS represents a spectrum of ischemic myocardial events that share similar pathophysiology; they include unstable angina/non–ST-segment elevation myocardial infarction (UA/NSTEMI), ST-segment elevation myocardial infarction (STEMI), and sudden cardiac death.

Atherosclerosis is a systemic disease involving the intima of large and medium-sized arteries, including the aorta, carotids, coronaries, and peripheral arteries, that is characterized by intimal thickening caused by the accumulation of cells and lipids (Fig. 53–1).1 Lipid accumulation results from an imbalance between the mechanisms responsible for the influx and efflux of lipids into the arterial wall.2 Secondary changes may occur in the underlying media and adventitia, particularly in advanced disease stages. The early atherosclerotic lesions might progress without compromising the lumen because of compensatory vascular enlargement (Glagovian remodeling).3 Importantly, the culprit lesions leading to ACS are usually mildly stenotic and therefore barely detected by angiography (Fig. 53–2).4 These high-risk, rupture-prone lesions usually have a large lipid core, a thin fibrous cap, and a high density of inflammatory cells (particularly at the shoulder region, where disruptions most often occur).

Figure 53–1.

Simplified diagram of the evolution of coronary atherosclerosis. Phases and morphology of lesion progression.

Figure 53–2.

Relationship of coronary stenosis severity (angiography) and presentation of acute coronary events from four studies with a total of 200 patients. ACS, acute coronary syndromes. Modified from Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657-671.

Recent evidence has highlighted the importance of lesion neovascularization and blood extravasation in plaque destabilization and plaque growth.5-7 Leaky vasa vasorum with the subsequent red blood cell extravasation has been postulated as a major source for intraplaque cholesterol deposition. This change in composition, characterized by increased extracellular cholesterol within the lipid core and excessive macrophage infiltration, increases the vulnerability of the atherosclerotic lesions. In fact, postmortem studies have shown a strong correlation between macrophage infiltration and increased vasa vasorum in human atherosclerotic lesions. Preexisting vasa vasorum in the adventitia are thought to spread into the intima, prompting intimal neovascularization.6 Elimination of neovascularization for plaque stabilization has been postulated as a novel target to treat patients with high-risk plaques.8 Inflammation is another important process that affects plaque progression, vulnerability, and subsequent thrombus formation. Inflammation could be considered as the link between atherosclerosis and thrombosis. ...

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