Does the basic pathology of Unstable Angina (UA), Non-ST-Elevation Myocardial Infarction (NSTEMI), and ST-Elevation Myocardial Infarction (STEMI) depend on rupture of the thin fibrin cap and subsequent thrombosis?

Pathophysiology of Unstable Angina, NSTEMI, and STEMI

Yes, the basic pathology of Unstable Angina (UA), Non-ST-Elevation Myocardial Infarction (NSTEMI), and ST-Elevation Myocardial Infarction (STEMI) primarily depends on atherosclerotic plaque disruption (rupture or erosion) and subsequent thrombosis. 1

Common Pathophysiological Mechanism

The 2025 ACC/AHA guidelines clearly define the pathophysiology of acute coronary syndromes (ACS):

• Progressive lipid accumulation and inflammation within an atherosclerotic plaque leads to plaque instability
• Rupture or erosion of the atherosclerotic plaque exposes plaque contents to circulation
• This exposure activates the coagulation cascade and subsequent thrombosis
• When occurring in epicardial coronary vessels, the resulting thrombus compromises myocardial blood flow
• The degree of flow reduction determines the clinical presentation along the ACS spectrum 1

Differences Between UA, NSTEMI, and STEMI

The clinical manifestation depends on the extent of coronary occlusion:

1. Unstable Angina:

   • Transient myocardial ischemia with diminished flow
   • No significant myonecrosis (normal cardiac troponin)
   • Typically caused by nonocclusive thrombus on disrupted plaque 1

2. NSTEMI:

   • Partially occluded coronary artery
   • Leads to subendocardial ischemia
   • Elevated biomarkers of myonecrosis (troponin)
   • Usually results in non-Q-wave MI 1

3. STEMI:

   • Completely occluded coronary vessel
   • Leads to transmural myocardial ischemia and infarction
   • Elevated biomarkers of myonecrosis
   • Usually results in Q-wave MI 1

Mechanisms of Plaque Disruption

Two primary mechanisms of plaque disruption have been identified:

1. Plaque Rupture:

   • Active rupture related to secretion of proteolytic enzymes by macrophages
   • Weakens the fibrous cap, typically at its thinnest point
   • More common in men 1

2. Plaque Erosion:

   • Surface erosion without deep rupture
   • More common in women (37% vs 18% in men) 1

Additional Pathophysiological Considerations

While plaque disruption and thrombosis represent the primary mechanism, other causes of ACS include:

• Dynamic obstruction (coronary spasm or vasoconstriction)
• Progressive mechanical obstruction to coronary flow
• Coronary arterial inflammation
• Coronary artery dissection
• Secondary UA (extrinsic factors increasing oxygen demand or decreasing supply) 1

Clinical Implications

Understanding this pathophysiology has direct implications for treatment:

• Antiplatelet and anticoagulant therapies target the thrombotic process
• Lipid-lowering therapies aim to stabilize vulnerable plaques
• Revascularization strategies (PCI or CABG) address the underlying obstruction 2

Important Caveats

• The pathophysiology of ACS is dynamic - patients can rapidly progress from one clinical condition to another during presentation and initial evaluation
• Not all myocardial infarctions follow this pathophysiology - Type 2 MI results from oxygen supply-demand mismatch without plaque disruption
• Other less common causes of myocardial ischemia include coronary artery spasm, embolism, and dissection 1

The recognition that plaque disruption and thrombosis represent the fundamental pathophysiology of ACS has revolutionized treatment approaches, shifting focus to early revascularization and aggressive antithrombotic therapy to improve outcomes and reduce mortality.