Pathophysiology of Atherosclerotic Carotid Disease

Carotid artery atherosclerosis is an important etiology of carotid artery stenosis and subsequent cerebrovascular events. Carotid atherosclerosis follows a pattern that begins with endothelial dysfunction, marked by impaired nitric oxide-mediated vasodilation and increased endothelial permeability, and is followed by intimal low-density lipoprotein (LDL) accumulation. Retained oxidized LDL results in a pro-inflammatory environment that results in inflammatory cell inflammation and foam cell formation, the basis of the fatty streak. Migrating medial vascular smooth muscle cells, which undergo phenotypic switching, lead to plaque growth and fibrous cap formation. The unique geometry of the carotid bifurcation contributes to the complex local hemodynamic environment and predisposes the carotid bifurcation to endothelial dysfunction. In later stages of atherosclerosis, higher wall shear stress erodes the fibrous cap and increases the risk of plaque rupture. Several parameters of carotid bifurcation geometry, including the bifurcation angle and relative diameters of the internal and common carotid arteries, also contribute to disturbed flow and atherosclerotic plaque development.