A Macro and Micro View of Coronary Vascular Insult in Ischemic Heart Disease

Atherosclerotic plaques are either concentric, producing a fixed degree of obstruction, or eccentric, with retention of an arc of normal vessel wall that allows changes in medial muscle tone to vary the degree of stenosis. Plaques may also either be solid and fibrous or may contain, in addition to fibrous thickening, a pool of extracellular cholesterol. Most subjects with ischemic heart disease have mixtures of all plaque types. The endothelium over established human plaques often shows focal denudation injury, with adhesion of a platelet monolayer not detectable by angiography. Larger thrombi are due either to superficial intimal injury, which is the progression of the endothelial denudation seen over otherwise static and intact plaques, or to deep intimal injury caused by plaque fissuring (rupture). Both forms of intimal injury expose collagen and von Willebrand factor to platelets. In deep injury, tears extend from the lumen into the depths of the intima and often enter a lipid pool; in consequence, thrombus initially forms within the plaque, thereby altering its configuration and expanding its volume. Many fissures will reseal at this stage, but the plaque is larger, and the process is an important cause of episodic sudden plaque growth. A proportion of plaque fissures are associated with the additional formation of a luminal thrombus, which may be either mural or occlusive. In life, transitions between mural and occlusive thrombi and vice versa occur rapidly and frequently. Mural thrombus is associated with distal embolization of platelet masses and, in some cases, is associated with cholesterol from the plaque. “Unstable” plaques undergoing fissure are associated with unstable angina, acute infarction, and a large proportion of sudden ischemic deaths. The relative sizes of intraplaque and intraluminal thrombi vary; when the former is large, much of the arterial obstruction may be caused by a thrombus that has been incarcerated within the plaque and that compresses the lumen from outside. Raised intimal flaps and extrusion of a plug of lipid debris into the lumen are further factors leading to occlusion in large or complex plaque fissures. Plaque fissuring is due to concentrations of circumferential tensile stress on the cap tissue, particularly in plaques containing a soft core of lipid; weakening of cap tissue by an infiltrate of macrophages is a contributory factor.