Impaired flow mediated dilatation as evidence of endothelial dysfunction in chronic atrial fibrillation: relationship to plasma von Willebrand factor and soluble E-selectin levels

Abstract

Background: Impaired endothelial-dependent flow-mediated dilatation (FMD) has been used to demonstrate endothelial dysfunction in a wide variety of cardiovascular disease, but previous studies have excluded patients with atrial fibrillation(AF). We therefore hypothesised that endothelial dysfunction exists in AF and that this could be demonstrated by impaired FMD, and related to plasma indices of endothelial damage/dysfunction [soluble E-selectin (sE-sel), von Willebrand factor (vWf), and soluble thrombomodulin (sTM)], as well as total body nitrate/nitrite product (NOx, a measure of endothelial nitric oxide production).

Methods: We studied 40 patients with chronic permanent AF, who were compared to 26 sinus rhythm controls. Patients with AF were stable on rate-control and antithrombotic medication and were fasted for the study. High-resolution ultrasound was used to measure right brachial artery diameter at rest, during reactive hyperaemia (endothelium-dependent flow-mediated dilatation) and following endothelium-independent, GTN-mediated dilatation.

Results: Baseline brachial artery diameter did not differ significantly between AF and healthy control subjects. FMD was significantly impaired in AF patients in comparison to healthy controls (8.9% in controls vs 0.0% in AF, p<0.0001). There was no significant difference in endothelium-independent (GTN-induced) dilatation between the groups. Only AF and male sex were independent predictors of impaired FMD on stepwise multiple regression analysis(p<0.0001). sE-sel and vWf were higher in AF than controls (p<0.05), and NOx levels did not reach significance (p=0.1416).

Conclusions: Endothelial dysfunction, as demonstrated by impairment of FMD and raised vWF and E-selectin, is present in AF. Such endothelial perturbation may contribute to the increased risk of stroke and thromboembolism in this common arrhythmia.