What is an unstable plaque?

What is an Unstable Plaque?

An unstable plaque is an atherosclerotic lesion characterized by a large lipid-rich core, a thin fibrous cap (typically <70 µm), high macrophage density, low smooth muscle cell content, and active inflammation that makes it prone to rupture, leading to acute coronary syndromes through thrombosis and vessel occlusion. 1

Structural Characteristics of Unstable Plaques

The vulnerability of an atherosclerotic plaque depends on specific compositional and architectural features rather than the degree of luminal stenosis:

• Large lipid-rich necrotic core with high concentrations of cholesteryl esters containing a high proportion of polyunsaturated fatty acids 1
• Thin fibrous cap measuring approximately 70 µm or less, which is far below the resolution of current imaging modalities (MDCT: 750 µm, MRI: 500-780 µm) 1
• High macrophage density with activated inflammatory cells concentrated at the plaque shoulder 1
• Low smooth muscle cell density resulting from apoptosis, which further weakens the structural integrity of the cap 1
• Disorganized collagen structure with reduced collagen and glycosaminoglycan concentrations 1
• High tissue factor concentration making the exposed core highly thrombogenic upon rupture 1

Mechanisms of Plaque Disruption

Plaque instability results from two complementary pathophysiologic processes:

Active Rupture

• Inflammatory enzyme degradation: Activated macrophages secrete metalloproteinases that actively dissolve collagen in the fibrous cap, creating a dynamic imbalance between collagen synthesis and degradation 1
• T-lymphocyte activation: These cells release cytokines that further activate macrophages and promote smooth muscle cell proliferation 1
• Smooth muscle cell apoptosis: Programmed cell death weakens the cap tissue and favors rupture 1

Passive Disruption

• Physical stress concentration: Circumferential wall stress concentrates at the weakest point of the fibrous cap, typically at the junction between the plaque and adjacent "normal" wall 1
• Biomechanical factors: The vulnerability depends on wall stress, location, size, and composition of the lipid core 1

Clinical Significance and Thrombotic Consequences

A critical insight is that most acute coronary syndromes arise from plaques causing only mild to moderate stenosis on angiography, not necessarily severe stenoses. 2

When plaque disruption occurs:

• Thrombosis initiation: The exposed lipid-rich core is highly thrombogenic, with greater tissue factor concentration than other plaque components 1
• Dynamic thrombotic process: Thrombosis and spontaneous clot lysis occur simultaneously, with associated vasospasm causing intermittent flow obstruction 2
• Microembolization: Platelet aggregates and plaque components embolize distally, releasing myocardial markers even without complete vessel occlusion 1
• Clinical spectrum: The degree of thrombosis determines presentation—transient ischemia (unstable angina), partial occlusion (NSTEMI), or complete occlusion (STEMI) 2

Distinguishing Unstable from Vulnerable Plaques

While often used interchangeably, there is a subtle distinction:

• Vulnerable plaque: A thin-cap fibroatheroma (TCFA) that is prone to rupture but has not yet disrupted 3
• Unstable plaque: A plaque that has already undergone disruption (rupture or erosion) with superimposed thrombosis 4, 3

Key Clinical Pitfalls

The most important caveat is that unstable plaques are not necessarily the most stenotic lesions. 2 Traditional angiography focusing solely on luminal narrowing will miss the majority of culprit lesions responsible for acute coronary syndromes. The qualitative aspects of plaque composition—particularly inflammation, lipid content, and cap thickness—are more important determinants of vulnerability than stenosis severity. 4

Current imaging modalities cannot directly visualize the thin fibrous cap due to resolution limitations, making identification of vulnerable plaques before rupture a significant clinical challenge. 1