Coronary vascular remodeling in association with endothelial dysfunction

Vascular remodeling has been demonstrated in advanced and early coronary artery disease. Whereas the endothelium may play a role in the adaptive process of vascular remodeling, it is not known if this process occurs in association with changes in coronary blood flow reserve. Early coronary atherosclerosis is characterized by endothelial dysfunction which is manifested by an abnormal coronary blood flow in response to the endothelium-dependent vasodilator acetylcholine. This study was designed to test the hypothesis that coronary vascular remodeling occurs in association with coronary endothelial dysfunction early in the development of coronary atherosclerosis. Thirty-six patients found to have normal coronary angiograms or mild coronary artery disease were studied. Acetylcholine was infused into the left anterior descending artery. Patients were divided into 2 groups based on their coronary blood flow response to acetylcholine. Intravascular ultrasound measurements of the proximal left anterior descending diameter and area were obtained. Vessel diameter and area were measured at the external elastic membrane and indexed to body surface area. Vessel diameter and area were greater in patients with abnormal than normal responses to acetylcholine (5.2 +/- 0.3 mm and 19.5 +/- 0.9 mm2 vs 3.9 +/- 0.3 mm and 12.3 +/- 1.0 mm2; p <0.02, respectively). This difference persisted when measurements were indexed to body surface area. The current study suggests in vivo in humans that coronary vascular remodeling characterized by enlargement of the proximal coronary arteries occurs in association with endothelial dysfunction early in the course of coronary artery disease.