Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Thromb Haemost. 2018 Apr;118(4):791-797. doi: 10.1055/s-0038-1636543. Epub 2018 Apr 4.
Survival of peripheral arterial disease (PAD) patients increased over the last decade due to increased use of secondary preventive medication and rapid revascularization of PAD patients. Angiogenetic markers such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and its receptor Tie-2 might be useful markers to assess the residual risk for mortality in PAD patients. The aim of this study was to evaluate angiogenetic markers for the prediction of mortality in a PAD cohort. For this purpose, 366 patients (mean age: 69 ± 10 years) with PAD Fontaine stage I or II were included and followed up over a 5-year study period. Serum Ang-2, Tie-2 and VEGF levels were measured by bead-based multiplex assay. All-cause mortality and major cardiovascular events (MACE) including all-cause death, non-fatal stroke and non-fatal myocardial infarction were analysed by Kaplan-Meier and Cox regression analyses after 5 years. Ang-2 was associated with Tie-2 ( = 0.151, = 0.006) and VEGF levels ( = 0.160, = 0.002). However, only Ang-2 was linked to all all-cause mortality in PAD patients (hazard ratio [HR]: 1.55 [1.23-2.15], = 0.008) even after adjustment for age and gender, haemoglobin A1c, low-density lipoprotein cholesterol, systolic blood pressure and glomerular filtration rate (HR: 1.44 [1.03-2.00], = 0.032). Furthermore, an association of Ang-2 and MACE in PAD patients (HR: 1.36 (1.03-1.78), = 0.028) was found. This result implies that Ang-2 might be used as an additional marker to stratify PAD patients to predict poor mid-term life expectancy.
由于二级预防药物的使用增加和外周动脉疾病 (PAD) 患者的快速血运重建，过去十年 PAD 患者的生存率有所提高。血管生成标志物，如血管内皮生长因子 (VEGF)、血管生成素-2 (Ang-2)及其受体 Tie-2，可能是评估 PAD 患者死亡残余风险的有用标志物。本研究旨在评估血管生成标志物在 PAD 患者中的预后作用。为此，纳入了 366 名 PAD Fontaine Ⅰ或Ⅱ期患者（平均年龄：69±10 岁），并进行了为期 5 年的随访。通过基于珠的多重分析测量血清 Ang-2、Tie-2 和 VEGF 水平。Kaplan-Meier 和 Cox 回归分析显示，5 年后全因死亡率和主要心血管事件 (MACE)，包括全因死亡、非致死性卒中及非致死性心肌梗死。Ang-2 与 Tie-2 相关（ = 0.151， = 0.006）和 VEGF 水平（ = 0.160， = 0.002）。然而，只有 Ang-2 与 PAD 患者的全因死亡率相关（风险比 [HR]：1.55 [1.23-2.15]， = 0.008），即使在调整年龄、性别、糖化血红蛋白、低密度脂蛋白胆固醇、收缩压和肾小球滤过率后也是如此（HR：1.44 [1.03-2.00]， = 0.032）。此外，还发现 Ang-2 与 PAD 患者的 MACE 相关（HR：1.36 [1.03-1.78]， = 0.028）。这一结果表明，Ang-2 可作为一种额外的标志物，用于分层 PAD 患者，以预测中期生存率不佳。
