What is burden reduction in the context of atherosclerotic plaque?

Burden Reduction in Atherosclerotic Plaque

Burden reduction refers to decreasing the total volume or size of atherosclerotic plaque buildup in the arteries through medical therapy, primarily achieved with intensive lipid-lowering treatments that can slow, halt, or even reverse plaque accumulation.

What Plaque Burden Means

• Atherosclerotic burden represents the total amount of plaque material—including lipids, inflammatory cells, and connective tissue—that has accumulated within arterial walls 1
• This accumulation causes arterial wall thickening that can significantly compromise blood flow through the vessel lumen 2
• The degree of coronary calcification correlates with the extent of total atherosclerotic burden, with cardiovascular risk increasing proportionally 3

How Burden Reduction Works

Lipid-Lowering Mechanisms

• Statins reduce plaque burden by lowering LDL cholesterol to very low levels, which has been demonstrated through intravascular ultrasound imaging studies to safely reduce overall atherosclerotic plaque volume 1
• PCSK9 inhibitors provide incremental effects beyond statins, showing positive effects not only on atherosclerotic burden but also on plaque composition, as demonstrated in the GLAGOV and HUYGENS studies 4, 1
• Intensive lipid-lowering therapy can stabilize and even reverse atherosclerotic burden in coronary circulation, challenging the previous notion that atherosclerosis was an irreversible condition 4

Anti-Inflammatory Effects

• Lipid-lowering agents demonstrate direct effects on plaque volume and composition that enhance plaque stabilization and/or regression beyond just reducing LDL cholesterol 5
• Statins and AT1 receptor blockers stabilize atherosclerotic plaques through reduction of inflammatory burden and suppression of metalloproteinase release 6
• These medications reduce the inflammatory processes that drive plaque progression, including macrophage infiltration and inflammatory marker production 5, 4

Clinical Significance

• Reducing plaque burden translates to decreased cardiovascular events including myocardial infarction, stroke, and cardiovascular death 1
• The NANOM trial demonstrated that photothermal destruction of atheroma tissue resulted in reduction of plaque volume down to 37.8% of initial plaque burden 7
• Despite maximal LDL cholesterol reduction, considerable residual cardiovascular risk remains in some patients, indicating the need for additional therapeutic approaches beyond lipid lowering 1

Measuring Burden Reduction

• Invasive imaging modalities like intravascular ultrasonography allow accurate serial quantification of atherosclerotic plaque volume changes over time 1, 2
• Coronary computed tomography angiography enables non-invasive assessment of overall atherosclerotic plaque burden and could guide personalized management strategies 1
• Novel imaging technology has allowed accurate evaluation of plaque progression and regression, vital for assessing intervention efficacy 2

Key Clinical Point

• Plaque burden reduction is distinct from plaque stabilization—burden reduction means actually shrinking the total plaque volume, while stabilization refers to making existing plaques less likely to rupture by modifying their composition (increasing fibrous cap thickness, reducing lipid core, decreasing inflammation) 5, 4