血浆胱抑素 B 与腹主动脉瘤及其后续手术修复的相关性：VIVA 试验的子研究。
Plasma Cystatin B Association With Abdominal Aortic Aneurysms and Need for Later Surgical Repair: A Sub-study of the VIVA Trial.
机构信息
Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Elitary Research Centre of Individualized Medicine of Arterial Disease, Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark.
出版信息
Eur J Vasc Endovasc Surg. 2018 Dec;56(6):826-832. doi: 10.1016/j.ejvs.2018.08.028. Epub 2018 Sep 24.
OBJECTIVE/BACKGROUND: The development of an abdominal aortic aneurysm (AAA) involves extensive extracellular matrix remodelling, leading to aortic wall weakening. This process is mediated by proteases, including cysteinyl cathepsins. Cystatins are their endogenous inhibitors. This study tested whether plasma cystatin B levels in patients with AAA differed from those of healthy controls.
METHODS
Plasma samples from patients with AAA and age matched controls were selected from the Viborg Vascular (VIVA) screening trial for AAA. Enzyme linked immunosorbent assay determined plasma cystatin B. T-test, logistic regression, Pearson's correlation and Cox regression tested whether plasma cystatin B correlates with AAA size and growth rate, or serves as a marker for AAA.
RESULTS
Plasma cystatin B levels were significantly higher in patients with AAA than in controls (p < 0.001). Logistic regression analysis showed that cystatin B tertile at baseline was associated with the presence of AAA before (odds ratio [OR] 1.656; p < 0.001) and after adjustment for peripheral arterial disease (PAD), chronic obstructive pulmonary disease (COPD), and previous ischaemic events (OR 1.526; p < 0.001). A t-test showed a significant association between cystatin B and PAD at screening, hospital diagnosis of COPD, previous atherosclerotic events, and use of low dose aspirin. Pearson's correlation test showed positive and significant associations between cystatin B and AAA size (r = 0.15; p < 0.001). Cox regression test showed that plasma cystatin B tertile at baseline was associated with later AAA surgical repair before (hazard ratio [HR] 1.387; p < 0.001) and after adjustment for PAD, COPD, previous ischaemic event, and maximum infrarenal aortic diameter (HR 1.523; p < 0.001).
CONCLUSION
In contrast to prior studies that showed that cystatin C is negatively associated with AAA development, this study demonstrated a positive association between cystatin B and AAA size and associations between cystatin B tertile at baseline and AAA presence and need for later surgical repair. It is possible that these two cystatins inhibit cathepsin activity and participate in AAA with different mechanisms.
目的/背景：腹主动脉瘤（AAA）的发展涉及广泛的细胞外基质重塑，导致主动脉壁变弱。这一过程由包括半胱氨酸蛋白酶在内的蛋白酶介导。胱抑素是它们的内源性抑制剂。本研究检测了 AAA 患者的血浆胱抑素 B 水平是否与健康对照组不同。
方法
从 Viborg Vascular（VIVA）AAA 筛查试验中选择 AAA 患者和年龄匹配的对照者的血浆样本。酶联免疫吸附测定法测定血浆胱抑素 B。T 检验、逻辑回归、皮尔逊相关和 Cox 回归检验了血浆胱抑素 B 是否与 AAA 大小和增长率相关，或是否作为 AAA 的标志物。
结果
AAA 患者的血浆胱抑素 B 水平明显高于对照组（p<0.001）。逻辑回归分析显示，基线时胱抑素 B 三分位与 PAD、COPD 和既往缺血事件校正前（比值比[OR]1.656；p<0.001）和校正后（OR 1.526；p<0.001）AAA 的存在相关。T 检验显示胱抑素 B 与筛查时的 PAD、医院诊断的 COPD、既往动脉粥样硬化事件以及低剂量阿司匹林的使用之间存在显著相关性。皮尔逊相关检验显示胱抑素 B 与 AAA 大小之间存在正相关且显著相关（r=0.15；p<0.001）。Cox 回归检验显示，基线时胱抑素 B 三分位与 PAD、COPD、既往缺血事件和肾下最大主动脉直径校正前（风险比[HR]1.387；p<0.001）和校正后（HR 1.523；p<0.001）AAA 的手术修复后存在相关性。
结论
与先前表明胱抑素 C 与 AAA 发展呈负相关的研究相反，本研究显示胱抑素 B 与 AAA 大小呈正相关，且基线时胱抑素 B 三分位与 AAA 的存在和随后需要手术修复之间存在相关性。这两种胱抑素可能通过不同的机制抑制组织蛋白酶活性并参与 AAA。
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