What is vulnerable plaque?

Vulnerable Plaque: Understanding the Culprit in Acute Coronary Syndromes

Vulnerable plaque is an atherosclerotic lesion characterized by a large lipid-rich core covered by a thin fibrous cap that is prone to rupture, leading to thrombosis and potentially causing acute coronary syndromes, myocardial infarction, or sudden cardiac death. 1

Definition and Characteristics

• Vulnerable plaque, also known as "thin-cap fibroatheroma" (TCFA), has a necrotic lipid core covered by a thin fibrous cap (less than 65 μm thick) that is infiltrated by macrophages 1
• The fibrous cap consists primarily of type I collagen and is in a dynamic state of balance between synthesis (modulated by growth factors) and degradation (by metalloproteases from activated macrophages) 1
• The lipid core contains a high concentration of cholesteryl esters with a high proportion of polyunsaturated fatty acids, which influences local platelet and thrombus formation 1
• These plaques often have low smooth muscle cell density, high macrophage density, and disorganized collagen matrix 1

Pathophysiology of Plaque Vulnerability

• Plaque disruption may occur through:
  • Active rupture: Related to secretion of proteolytic enzymes by macrophages that weaken the fibrous cap 1
  • Passive rupture: Related to physical forces occurring at the weakest point of the fibrous cap, typically at the junction of the plaque and adjacent normal wall 1
• Inflammation plays a key role in plaque instability:
  • Macrophage infiltration and activated T-lymphocytes are consistently found at sites of plaque rupture 1
  • T-lymphocytes release cytokines that activate macrophages and promote smooth muscle cell proliferation 1
  • Apoptosis of smooth muscle cells can further weaken the cap tissue and favor plaque rupture 1

Clinical Significance

• Vulnerable plaques are the primary cause of acute coronary syndromes and myocardial infarction 1, 2
• Importantly, vulnerable plaques often cause only mild to moderate stenosis (less than 75% cross-sectional narrowing or less than 50% diameter stenosis) and may not be visible on conventional angiography 2, 3
• These plaques are most frequently found in the proximal left anterior descending coronary arteries and less commonly in the proximal right or left circumflex coronary arteries 3
• When a vulnerable plaque ruptures, it exposes the highly thrombogenic lipid core to blood, initiating clot formation that can rapidly occlude the vessel 1

Imaging and Detection

• Traditional angiography has limited ability to identify vulnerable plaques due to their often non-obstructive nature 2
• Advanced imaging techniques for vulnerable plaque detection include:
  • Intravascular ultrasound (IVUS): Provides two-dimensional cross-sectional images of arterial walls and can help assess plaque burden and composition 1, 2
  • Optical coherence tomography (OCT): Offers superior resolution for visualizing thin fibrous caps but has limited penetration depth 1, 2
  • CT and MRI: Can identify lipid-rich tissue but have resolution limitations for small plaque structures 1
• Newer techniques under development include:
  • Palpography (IVUS-derived): Can differentiate between deformable and non-deformable tissue 4
  • Thermography: Assesses temperature heterogeneity as an indicator of plaque inflammation 4
  • Near-infrared spectroscopy (NIR): Can identify lipid-loaded plaques 4

Risk Factors and Biomarkers

• Vulnerable plaques are more common in:
  • Patients with high serum total cholesterol and high total cholesterol to HDL ratio 3
  • Women over 50 years of age 3
  • Patients with elevated levels of high-sensitivity C-reactive protein 3
• Circulating inflammatory markers such as C-reactive protein and interleukin-6 correlate with the clinical course and outcome of acute coronary syndromes 1

Clinical Implications

• Atherosclerosis is not a continuous, linear process but rather a disease with alternate phases of stability and instability 1
• Sudden and unpredictable changes in symptoms appear to be related to plaque disruption 1
• The risk of plaque rupture is based more on plaque composition than plaque volume or degree of stenosis 1
• No validated biomarker or imaging technique is currently available that can reliably predict the risk of plaque rupture in individual patients 1
• Detection of arterial inflammation through imaging techniques like PET is being explored as an approach to identify patients at highest risk of plaque rupture 1

Understanding vulnerable plaque characteristics is crucial for developing strategies to identify at-risk patients and prevent acute coronary events before they occur.