Edlinger Christoph, Lichtenauer Michael, Wernly Bernhard, Pistulli Rudin, Paar Vera, Prodinger Christine, Krizanic Florian, Thieme Marcus, Kammler Jürgen, Jung Christian, Hoppe Uta C, Schulze P Christian, Kretzschmar Daniel
Division of Cardiology, Department of Internal Medicine II, Paracelsus Medical University of Salzburg, Salzburg, Austria.
Department of Internal Medicine I, Friedrich Schiller University Jena, Jena, Germany.
Heart Vessels. 2019 Jun;34(6):976-983. doi: 10.1007/s00380-018-1315-1. Epub 2018 Dec 7.
Peripheral arterial disease (PAD) is one of the most common manifestations of systemic atherosclerosis. The prevalence of unrecognized PAD is high, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular events. Inflammatory processes play an important role in the disease initiation as well as in the disease progression. Vascular cell adhesion molecule 1 (VCAM-1), a biomarker of endothelial dysfunction, appears to be an important mediator in inflammatory processes. Therefore, we hypothesized that in patients with PAD, circulating VCAM-1 might be elevated due to its function in mediating adhesion of immune cells to the vascular endothelium in the process of endothelial dysfunction and inflammation, and, therefore, applicable as a diagnostic biomarker. A total of 126 non-consecutive patients were enrolled in this study, of whom 51 patients had typical clinical manifestations of PAD and as controls 75 patients with no history of PAD or cardiovascular disease. All serum samples were obtained either during hospitalization or during out-patient visits and analyzed for VCAM-1 by the ELISA. Compared with controls, median levels of VCAM-1 were significantly elevated in patients suffering from PAD (953 vs. 1352 pg/ml; p < 0.001). Furthermore, VCAM-1 appeared to be highly discriminative for the detection of PAD (AUC = 0.76; CI 0.67-0.83). We could not observe dynamics related to increasing disease stages according to Rutherford classes in patients with apparent PAD. VCAM-1 was shown to be a potential discriminator and biomarker for the severity of systemic atherosclerosis. In a logistic regression analysis, VCAM-1 was robustly associated with the diagnosis of PAD, even after correction for clinically relevant cofounders (namely age, arterial hypertension, diabetes and LDL levels). Thusly, VCAM-1 might serve as a biomarker for PAD screening and detection.
外周动脉疾病(PAD)是全身动脉粥样硬化最常见的表现之一。未被识别的PAD患病率很高,导致缺乏发现心血管事件高危人群的机会。炎症过程在疾病的发生和发展中起着重要作用。血管细胞粘附分子1(VCAM-1)作为内皮功能障碍的生物标志物,似乎是炎症过程中的重要介质。因此,我们推测,在PAD患者中,循环中的VCAM-1可能会升高,因为它在血管内皮功能障碍和炎症过程中介导免疫细胞与血管内皮的粘附,因此可作为一种诊断生物标志物。本研究共纳入126例非连续患者,其中51例患者有典型的PAD临床表现,75例无PAD或心血管疾病病史的患者作为对照。所有血清样本均在住院期间或门诊就诊时采集,并通过酶联免疫吸附测定法(ELISA)分析VCAM-1。与对照组相比,PAD患者的VCAM-1中位数水平显著升高(953对1352 pg/ml;p<0.001)。此外,VCAM-1似乎对PAD的检测具有高度的鉴别性(曲线下面积[AUC]=0.76;可信区间[CI] 0.67-0.83)。在明显患有PAD的患者中,我们未观察到与根据卢瑟福分级增加的疾病阶段相关的动态变化。VCAM-1被证明是全身动脉粥样硬化严重程度的潜在鉴别指标和生物标志物。在逻辑回归分析中,即使校正了临床相关的混杂因素(即年龄、动脉高血压、糖尿病和低密度脂蛋白水平),VCAM-1仍与PAD的诊断密切相关。因此,VCAM-1可能作为PAD筛查和检测的生物标志物。