Li Ben, Djahanpour Niousha, Zamzam Abdelrahman, Syed Muzammil H, Jain Shubha, Abdin Rawand, Qadura Mohammad
Division of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Canada.
Department of Medicine, McMaster University, Hamilton, Canada.
Heliyon. 2023 Sep 15;9(9):e20166. doi: 10.1016/j.heliyon.2023.e20166. eCollection 2023 Sep.
Angiogenesis plays an important role in peripheral artery disease (PAD) and angiogenesis-related proteins may act as prognostic biomarkers. This study assesses the potential for angiogenesis-related proteins to predict adverse events associated with PAD.
This was a case-control study. Patients with PAD (n = 250) and without PAD (n = 125) provided blood samples and were followed prospectively for three years. Concentrations of 17 angiogenesis-related proteins were measured in plasma. The incidence of major adverse limb event (MALE), defined as a composite of major amputation or vascular intervention, was the primary outcome. Worsening PAD status, defined as a drop in ankle brachial index ≥ 0.15, was the secondary outcome. Multivariable regression adjusted for baseline characteristics was conducted to determine the prognostication value of angiogenesis-related proteins in predicting MALE.
Relative to patients without PAD, 8 proteins related to angiogenesis were expressed differentially in PAD patients. Worsening PAD status and MALE were observed in 52 (14%) and 83 (22%) patients, respectively. Hepatocyte growth factor (HGF) was the most reliable predictor of MALE (adjusted HR 0.79, 95% CI 0.15-0.86). Compared to individuals with high HGF, patients with low HGF had a decreased three-year freedom from MALE [66% vs 88%, p = 0.001], major amputation [93% vs 98%, p = 0.023], vascular intervention [68% vs 88%, p = 0.001], and worsening PAD status [81% vs 91%, p = 0.006].
Measuring plasma levels of HGF in individuals with PAD can assist in identifying patients at elevated risk of adverse events related to PAD who may benefit from additional evaluation or treatment.
血管生成在周围动脉疾病（PAD）中起重要作用，与血管生成相关的蛋白质可能作为预后生物标志物。本研究评估与血管生成相关的蛋白质预测PAD相关不良事件的潜力。
这是一项病例对照研究。患有PAD的患者（n = 250）和未患PAD的患者（n = 125）提供血样，并进行了为期三年的前瞻性随访。测定血浆中17种与血管生成相关的蛋白质的浓度。主要不良肢体事件（MALE）的发生率定义为大截肢或血管介入的综合结果，是主要结局。PAD状态恶化定义为踝臂指数下降≥0.15，是次要结局。进行了针对基线特征调整的多变量回归分析，以确定与血管生成相关的蛋白质在预测MALE方面的预后价值。
与未患PAD的患者相比，8种与血管生成相关的蛋白质在PAD患者中差异表达。分别有52例（14%）和83例（22%）患者出现PAD状态恶化和MALE。肝细胞生长因子（HGF）是MALE最可靠的预测因子（调整后HR 0.79，95%CI 0.15 - 0.86）。与HGF水平高的个体相比，HGF水平低的患者三年无MALE的自由度降低[66%对88%，p = 0.001]，大截肢[93%对98%，p = 0.023]，血管介入[68%对88%，p = 0.001]，以及PAD状态恶化[81%对91%，p = 0.006]。
测量PAD患者血浆中HGF水平有助于识别与PAD相关不良事件风险升高的患者，这些患者可能从进一步评估或治疗中获益。
