Local Association Between Endothelial Dysfunction and Intimal Hyperplasia: Relevance in Peripheral Artery Disease

BACKGROUND: Endothelial dysfunction is a key factor in the development of atherosclerosis. Commonly, endothelial function is determined in the brachial artery, whereas patients with peripheral artery disease (PAD) present with lower limb atherosclerosis. We hypothesized that in PAD, a segmental or local association exists between endothelial dysfunction and atherosclerotic structural changes. METHODS AND RESULTS: We used ultrasound to study endothelial function as flow‐mediated vasodilation, intima media thickness, and local stiffness of the superficial femoral artery (SFA) and brachial artery (BA). PAD patients with symptomatic SFA or below‐the‐knee disease were compared with age‐matched patients without PAD and young healthy controls. PAD patients with SFA or below‐the‐knee disease exhibited endothelial dysfunction of the proximal SFA (flow‐mediated vasodilation: 3.9±0.6%, 3.7±0.6%) compared with healthy controls (7.4±1.0%) and patients without PAD (5.4±0.6%). Brachial artery flow‐mediated vasodilation values were not different in PAD patients with SFA or below‐the‐knee disease compared with patients without PAD, but they were significantly lower than those of healthy controls. Endothelial dysfunction correlated with increased intima media thickness or plaque thickness at the site of flow‐mediated vasodilation measurement across vascular sites. In PAD patients with SFA disease, SFA flow‐mediated vasodilation was further impaired within and distal to stenosis (prestenosis 3.9±0.6%, intrastenosis 2.3±0.7%, poststenosis 2.5±0.6%) and recovered within 24 hours after SFA balloon angioplasty to prestenotic values but not to the brachial artery or SFA values in patients without PAD or controls. CONCLUSION: A close association exists between local endothelial function and atherosclerotic structural remodeling, suggesting that in PAD, local and segmental factors—in addition to systemic factors—influence local endothelial function. Our data point toward a pathophysiological role for lower extremity endothelial dysfunction in PAD.