Pathophysiology of Plaque in Acute Coronary Syndrome

Introduction to Acute Coronary Syndromes

• Acute coronary syndromes result from atherosclerotic plaque disruption with superimposed thrombosis, vasoconstriction, and distal microembolization that reduces myocardial oxygen supply 1, 2

The Vulnerable Plaque: Structural Characteristics

• The plaques most prone to causing ACS have distinct structural features, including a large lipid-rich core with high concentrations of cholesteryl esters, a thin fibrous cap, low smooth muscle cell density, and high macrophage density 3, 4
• The American Heart Association notes that three-quarters of infarct-related thrombi develop over plaques causing only mild to moderate stenosis on angiography, not necessarily severe stenoses 5, 6

Mechanisms of Plaque Disruption

• Plaque disruption occurs through two primary mechanisms: active rupture and passive disruption, with inflammation playing a central role in the process 3, 4, 7
• Macrophages secrete metalloproteinases that actively dissolve collagen, weakening the fibrous cap, and the lipid core forms through active collagen dissolution by these enzymes 3, 4

The Thrombotic Cascade

• Once plaque disruption occurs, a dynamic thrombotic process unfolds, including exposure of thrombogenic material, coagulation cascade activation, platelet adhesion and aggregation, and fibrin stabilization 1, 2, 8
• The European Society of Cardiology notes that the thrombotic response is dynamic, with thrombosis and spontaneous clot lysis occurring simultaneously, often with associated vasospasm, causing intermittent flow obstruction 5, 6

Clinical Spectrum Based on Pathophysiology

• The degree of thrombosis and vessel occlusion determines the clinical presentation, with unstable angina resulting from transient ischemia, NSTEMI from partially occlusive thrombus, and STEMI from complete occlusive thrombus 1, 2, 8, 9
• The American College of Cardiology recommends considering the clinical spectrum of ACS when diagnosing and treating patients 1, 2, 8, 9

Temporal Dynamics and Triggers

• There is frequently a delay of up to 2 weeks between plaque rupture and clinical consequences, reflecting the dynamic nature of thrombosis and lysis occurring at the plaque site 5, 6
• Specific triggers for plaque disruption include circadian variation, physical or emotional stress, and other factors that increase sympathetic stimulation and vasoconstriction 5, 6