Introduction to Angina Pectoris

• Angina pectoris, commonly referred to as angina, is a condition characterised by chest pain or discomfort due to decreased blood flow to the heart muscle.
• It occurs when there is an imbalance between the heart’s oxygen demand and the supply it receives from the coronary arteries.
• Stable angina is the most common form, typically occurring during physical exertion or stress and subsiding with rest or medication. The pain is predictable, similar to previous episodes, and generally lasts less than five minutes.

Myocardial Oxygen Supply and Demand

• Angina results from an imbalance in myocardial oxygen supply and demand.
  • Increased Oxygen Demand:
    • Elevated heart rate
    • High systolic blood pressure
    • Increased myocardial wall tension
    • Enhanced myocardial contractility
  • Decreased Oxygen Supply:
    • Coronary artery narrowing or obstruction
    • Reduced collateral blood flow
    • Decreased perfusion pressure
    • Elevated heart rate (shortens diastolic filling time)
• Stable angina symptoms usually arise when plaque stenosis obstructs 70–80% of the coronary artery lumen, but symptoms can occur with less obstruction if additional factors, such as vasospasm or thrombosis, are present.

Atherosclerosis and Endothelial Dysfunction

• The most common cause of stable angina is atherosclerosis, a chronic inflammatory disease characterised by plaque build-up in the arterial walls.
• Endothelial Dysfunction:
  • The endothelium regulates vascular tone and prevents clot formation.
  • Dysfunction, triggered by risk factors such as smoking, hypertension, and hyperlipidemia, disrupts these functions, leading to:
    • Reduced nitric oxide (NO) production, a potent vasodilator.
    • Increased production of vasoconstrictive factors like endothelin and angiotensin II.
    • Platelet and leukocyte activation, contributing to inflammation and plaque formation.

Plaque Development and Progression

1. Early Stages:
   • Fatty streaks form from the accumulation of lipids, macrophages (foam cells), and other cells within the intima (innermost layer) of the artery.
2. Progression:
   • The plaque evolves through:
     • Lipid accumulation, forming a lipid-rich core.
     • Smooth muscle cell death and macrophage build-up, contributing to the core.
     • Formation of a fibrous cap from smooth muscle cells and extracellular matrix.
     • Advanced lesions develop with necrotic cores and calcification due to ongoing inflammation, cell death, and hypoxia.
3. Glagovian Remodelling:
   • In some cases, the artery remodels outward to accommodate the growing plaque, maintaining luminal diameter and masking stenosis severity on angiography.

Plaque Vulnerability and Rupture

• Vulnerable Plaques:
  • Large lipid-rich necrotic core
  • Thin fibrous cap
  • High inflammatory activity
• These plaques are prone to rupture, which can trigger thrombus formation and acute coronary syndromes, such as myocardial infarction.
• Triggers for Plaque Rupture:
  • Physical exertion
  • Psychological stress
  • Diurnal variations in coagulation and autonomic vascular tone

Biomarkers in Angina

• Biomarkers help identify individuals at risk of or with existing coronary artery disease.
  • Inflammatory Markers: CRP, IL-6, TNF-α, myeloperoxidase
  • Markers of Plaque Erosion: Mast cells
  • Thrombosis Markers: Fibrinogen, thromboxane B2
  • Lipid-Associated Markers: LDL-C, oxidised LDL, triglycerides
  • Markers of Endothelial Dysfunction: Adhesion molecules, von Willebrand factor
  • Plaque Stability Markers: MMPs, GDF-15
  • Metabolic Markers: HbA1c
  • Markers of Neovascularisation: Stromal-derived factor 1
  • Genetic Markers: SNPs associated with lipid metabolism and platelet function

Conclusion

Understanding the pathophysiology of angina is crucial for pharmacy students to provide optimal patient care. This knowledge informs medication choices, patient education on lifestyle modifications, and strategies for mitigating the progression of coronary artery disease.

References

1. Mayo Clinic. (n.d.). Angina: Symptoms and Causes. Retrieved from Mayo Clinic.
2. Sharma, S., & Bhattarai, B. (2021). Angina Pectoris. In StatPearls. StatPearls Publishing. Retrieved from StatPearls.
3. British Journal of Cardiology. (2020). Angina Module 3: Pathophysiology. Retrieved from British Journal of Cardiology.
4. MSD Manual. (n.d.). Angina Pectoris. Retrieved from MSD Manual.