Freestone Bethan, Chong Aun Yeong, Nuttall Sarah, Lip Gregory Y H
Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, England, UK.
Thromb Res. 2008;122(1):85-90. doi: 10.1016/j.thromres.2007.09.008. Epub 2007 Nov 8.
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).
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.
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).
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.
内皮依赖性血流介导的血管舒张功能(FMD)受损已被用于证明多种心血管疾病中的内皮功能障碍,但以往研究排除了心房颤动(AF)患者。因此,我们假设AF患者存在内皮功能障碍,这可通过FMD受损来证明,并与内皮损伤/功能障碍的血浆指标[可溶性E选择素(sE-sel)、血管性血友病因子(vWf)和可溶性血栓调节蛋白(sTM)]以及全身硝酸盐/亚硝酸盐产物(NOx,内皮一氧化氮生成的指标)相关。
我们研究了40例慢性持续性AF患者,并与26例窦性心律对照者进行比较。AF患者在心率控制和抗血栓药物治疗下病情稳定,且为进行研究而禁食。使用高分辨率超声测量静息时、反应性充血期间(内皮依赖性血流介导的血管舒张)以及内皮非依赖性、硝酸甘油介导的血管舒张后右肱动脉直径。
AF患者与健康对照者的基线肱动脉直径无显著差异。与健康对照者相比,AF患者的FMD显著受损(对照者为8.9%,AF患者为0.0%,p<0.0001)。两组之间内皮非依赖性(硝酸甘油诱导的)血管舒张无显著差异。在逐步多元回归分析中,只有AF和男性是FMD受损的独立预测因素(p<0.0001)。AF患者的sE-sel和vWf高于对照者(p<0.05),而NOx水平无统计学意义(p=0.1416)。
AF患者存在内皮功能障碍,表现为FMD受损以及vWF和E选择素升高。这种内皮紊乱可能导致这种常见心律失常患者中风和血栓栓塞风险增加。