Prognostic Value of Coronary Vascular Endothelial Dysfunction

TLDR

Coronary vascular function testing has not yet been shown to identify high‑risk patients within a relatively low‑risk population. This study examined whether coronary endothelial function predicts acute, unpredictable cardiovascular events in patients with and without coronary atherosclerosis. In 308 patients undergoing cardiac catheterization, ΔCVR and epicardial diameter were measured with intracoronary acetylcholine to assess endothelium‑dependent function, while sodium nitroprusside and adenosine evaluated endothelium‑independent responses, and patients were followed for an average of 46 months. ΔCVR and epicardial constriction responses to acetylcholine independently predicted adverse events, and patients with the best microvascular and epicardial responses had improved survival, whereas endothelium‑independent responses were not predictive.

Abstract

Background — Whether patients at increased risk can be identified from a relatively low-risk population by coronary vascular function testing remains unknown. We investigated the relationship between coronary endothelial function and the occurrence of acute unpredictable cardiovascular events (cardiovascular death, myocardial infarction, stroke, and unstable angina) in patients with and without coronary atherosclerosis (CAD). Methods and Results — We measured the change in coronary vascular resistance (ΔCVR) and epicardial diameter with intracoronary acetylcholine (ACh, 15 μg/min) to test endothelium-dependent function and sodium nitroprusside (20 μg/min) and adenosine (2.2 mg/min) to test endothelium-independent vascular function in 308 patients undergoing cardiac catheterization (132 with and 176 without CAD). Patients underwent clinical follow-up for a mean of 46±3 months. Acute vascular events occurred in 35 patients. After multivariate analysis that included CAD and conventional risk factors for atherosclerosis, ΔCVR with ACh ( P =0.02) and epicardial constriction with ACh ( P =0.003), together with increasing age, CAD, and body mass index, were independent predictors of adverse events. Thus, patients in the tertile with the best microvascular responses with ACh and those with epicardial dilation with ACh had improved survival by Kaplan-Meier analyses in the total population, as did those in the subset without CAD. Similar improvement in survival was also observed when all adverse events, including revascularization, were considered. Endothelium-independent responses were not predictive of outcome. Conclusions — Epicardial and microvascular coronary endothelial dysfunction independently predict acute cardiovascular events in patients with and without CAD, providing both functional and prognostic information that complements angiographic and risk factor assessment.