Onset of myocardial ischemia depends not only on the extent and severity of fixed atherosclerotic disease but also on dynamic changes in coronary plaque morphology. In most patients, unstable angina, infarction, and sudden cardiac death occur because of abrupt plaque change followed by thrombosis—hence the term acute coronary syndrome (
Fig. 11.7
The initiating event is typically a sudden disruption (ranging from erosion to rupture) of a partially occlusive plaque. More than one mechanism of injury may be involved: rupture, fissuring, or ulceration of plaques expose
OBSTRUCTION/? EMBOLI (Acute transmural myocardial (Unstable angina, or acute infarction or sudden death) subendocardial myocardial infarction or sudden death)
Fig. 11.7 Diagramofsequentialprogressionofcoronaryarterylesionsleadingtovariousacutecoronarysyndromes.(Modified and redrawn from Schoen FJ: Interventionalandsurgicalcardiovascularpathology:clinicalcorrelationsandbasicprinciples,Philadelphia, 1989, Saunders, p 63.) highly thrombogenic constituents or underlying subendothelial basement membrane, leading to rapid thrombosis. In addition, hemorrhage into the core of plaques can expand plaque volume, thereby acutely exacerbating the degree of luminal occlusion.
Factors that trigger plaque erosion include endothelial injury and apoptosis, likely attributable to some combination of inflammatory and toxic exposures. Acute plaque rupture, on the other hand, involves factors that influence plaque susceptibility to disruption by mechanical stress. These include intrinsic aspects of plaque composition and structure (Chapter 10) and extrinsic factors, such as blood pressure and platelet reactivity:
Plaques that contain large atheromatous cores or have thin overlying fibrous caps are more likely to rupture and are therefore termed vulnerable. Fissures frequently occur at the junction of the fibrous cap and the adjacent normal plaque-free arterial segment, where the mechanical stresses are highest and the fibrous cap is thinnest. Fibrous caps also are continuously remodeling; their overall balance of collagen synthesis versus degradation determines mechanical strength and plaque stability. Collagen is produced by smooth muscle cells and degraded by the action of metalloproteases elaborated by macrophages. Consequently, atherosclerotic lesions with a paucity of smooth muscle cells or large numbers of inflammatory cells are vulnerable to rupture. Of interest, statins (inhibitors of hydroxymethylglutaryl Co-A reductase, a key enzyme in cholesterol synthesis) can provide additional benefit in CAD and IHD by reducing plaque inflammation and increasing plaque stability, effects distinct from and their primary cholesterol-lowering activity.
Influences extrinsic to the plaque also are important. Adrenergic stimulation can put physical stress on the plaque by causing hypertension or local vasospasm. Indeed, the surge in adrenergic stimulation associated with awakening and rising may underlie the observation that the incidence of acute MI is highest between 6 AM and 12 noon. Intense emotional stress also leads to adrenergic stimulation, explaining the association of natural catastrophes such as earthquakes and floods with secondary waves of MIs in susceptible individuals.