Hamasaki, Shuichi

Background —Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function. Methods and Results —Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events ( P <0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death. Conclusions —Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.

Abstract — Coronary vascular remodeling and altered endothelial function have been described in the early stages of native atherosclerosis. The purpose of this study was to evaluate the association between cholesterol-lowering therapy and coronary vascular remodeling and endothelial function in patients with normal or mildly diseases coronary arteries. Patients (N=101) with normal or mildly diseased coronary arteries by coronary angiography underwent intravascular ultrasound examination of the left anterior descending coronary artery. Vessel and lumen area, atherosclerotic plaque area, and plaque morphology were evaluated. Vascular reactivity was examined with the use of intracoronary adenosine, acetylcholine, and nitroglycerin. Patients were divided into 3 groups based on the total cholesterol levels: group 1 (n=25), patients with a history of hypercholesterolemia adequately treated (total cholesterol <240 mg/dL); group 2 (n=26), patients with hypercholesterolemia not adequately controlled (total cholesterol ≥240 mg/dL); and group 3 (n=50), patients without hypercholesterolemia. Vessel area and lumen area were significantly greater in groups 1 and 3 than in group 2 (for respective values in groups 1, 2, and 3: vessel area 11.9±0.5, 10.6±0.4, and 11.8±0.4 mm 2 , both P <0.05; lumen area 8.3±0.4, 6.9±0.3, and 8.9±0.3 mm 2 , both P <0.01). However, plaque areas in groups 1 and 2 were similar. Furthermore, acetylcholine-induced percent increases in coronary blood flow were significantly greater in groups 1 and 3 than in group 2 (for respective values in groups 1, 2, and 3: 70.5±20.1%, 22.8±13.7%, and 68.6±14.8%, both P <0.05). Cholesterol-lowering treatment is associated with an improvement in coronary lumen area that results not from a decrease in plaque area but from an increase in vessel area, reflecting vascular remodeling. Additionally, this adaptive process may occur in association with an improvement of endothelium-dependent vasodilation of the resistance coronary artery.