Atherosclerosis is a chronic condition where fatty deposits, called plaque, accumulate inside blood vessels. These deposits can narrow the artery over time, restricting blood flow. However, the most dangerous plaques are structurally unstable and do not necessarily cause the most severe narrowing. This type of formation, known as vulnerable plaque, has a high risk of sudden rupture, which is the direct cause of most acute cardiovascular events.
The Distinct Anatomy of Vulnerable Plaque
The structure of a vulnerable plaque is defined by features that compromise its mechanical stability. It is characterized by a large, soft, necrotic lipid core composed primarily of cholesterol and cellular debris. This core is highly inflammatory and makes the structure intrinsically unstable.
Separating this volatile core from the bloodstream is the fibrous cap, a thin, fragile layer. A cap thickness less than 65 micrometers is highly predictive of rupture risk, marking the plaque as a thin-cap fibroatheroma (TCFA). Chronic inflammation, driven by immune cells like macrophages, further weakens this thin cap.
Macrophages within the cap secrete proteolytic enzymes, such as matrix metalloproteinases. These enzymes actively degrade the collagen and extracellular matrix that provides the cap’s strength. This process transforms the cap into a brittle, weak barrier over the pro-thrombotic lipid core, resulting in an inherently unstable anatomy.
The Mechanism of Plaque Rupture
An acute event, such as a heart attack or stroke, begins with the mechanical failure of the thin fibrous cap. The cap is constantly subjected to mechanical stress from pulsing blood flow and arterial wall movement. When internal pressure and external stresses exceed the tensile strength of the weakened cap, a fissure or tear occurs, typically at the cap’s shoulder region where stress is highest.
Rupture immediately exposes the highly thrombogenic contents of the lipid core to the circulating blood. The core material contains high concentrations of tissue factor, a powerful molecule that rapidly triggers the coagulation cascade. Platelets instantly aggregate at the injury site, attempting to seal the tear.
This rapid platelet aggregation and fibrin formation leads to the swift creation of a thrombus, or blood clot, over the rupture site. The resulting blood clot can quickly grow large enough to completely block the artery, halting blood flow to the downstream heart muscle or brain tissue. This sudden, complete blockage, rather than gradual narrowing, is the primary mechanism of an acute coronary syndrome or ischemic stroke.
Identifying Vulnerable Plaque
Standard diagnostic tools like conventional angiography focus on the degree of stenosis, or artery narrowing. Since vulnerable plaques often cause only mild to moderate blockages, specialized advanced imaging techniques are necessary. These methods visualize the specific structural features of the plaque and assess the quality and composition of the arterial wall, looking past the mere size of the blockage.
Intravascular Ultrasound (IVUS)
Intravascular Ultrasound (IVUS) uses a catheter-based ultrasound transducer to produce cross-sectional images of the vessel wall. IVUS measures total plaque burden and identifies positive vessel remodeling, where the artery wall expands outward to compensate for plaque growth. However, its resolution, typically around 100 micrometers, is often insufficient to precisely measure the thinness of the fibrous cap.
Optical Coherence Tomography (OCT)
Optical Coherence Tomography (OCT) offers a much higher spatial resolution, less than 20 micrometers, which is sufficient to accurately measure the fibrous cap thickness. OCT is the preferred method for identifying the thin-cap fibroatheroma (TCFA) and quantifying the size of the lipid core. Non-invasive Computed Tomography Angiography (CTA) can also suggest high-risk plaque features, such as low-attenuation plaque (indicating high lipid content) and the “napkin-ring sign,” which are markers for vulnerability.
Therapeutic Strategies for Stabilization
The primary goal of treatment for vulnerable plaque is stabilization, converting the high-risk lesion into a more benign one, rather than removal. High-intensity statin therapy is central to this strategy, working through mechanisms beyond simple cholesterol reduction. Statins reduce the lipid content within the necrotic core, causing it to shrink and become less inflammatory.
Statin therapy also promotes an increase in fibrous cap thickness, making the barrier more resistant to rupture. This stabilization is achieved by reducing the activity of inflammatory macrophages and decreasing the secretion of matrix-degrading enzymes within the plaque. The resulting thicker cap and smaller, less volatile core significantly lower the risk of an acute event.
Management of other cardiovascular risk factors also aids stabilization. Controlling high blood pressure reduces the mechanical stress placed on the fibrous cap, lessening the chance of a tear. Lifestyle changes, including smoking cessation and regular physical activity, decrease systemic inflammation, which reduces pro-inflammatory cells and enzymes within the plaque.