Long-Term Follow-Up of Patients With Mild Coronary Artery Disease and Endothelial Dysfunction

TLDR

Coronary endothelial dysfunction, marked by a vasoconstrictive response to acetylcholine, is an early phase of atherosclerosis but its long‑term outcomes remain poorly understood. This study aimed to determine the long‑term outcomes of patients with mild coronary artery disease stratified by endothelial function. In a cohort of 157 patients with mild CAD, endothelial function was assessed by graded intracoronary acetylcholine, adenosine, and nitroglycerin testing and intracoronary ultrasound, and patients were categorized into normal, mild, or severe dysfunction groups. During a mean 28‑month follow‑up, none of the patients with normal or mild dysfunction experienced cardiac events, whereas 14% of those with severe dysfunction had 10 events, indicating that severe endothelial dysfunction predicts increased cardiac events even without obstructive disease.

Abstract

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.