Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands.
JACC Cardiovasc Imaging. 2012 Dec;5(12):1201-10. doi: 10.1016/j.jcmg.2012.01.023.
This study sought to investigate the association between thrombin generation in plasma and the presence and severity of computed tomography angiographically defined coronary atherosclerosis in patients with suspected coronary artery disease (CAD).
Besides its pivotal role in thrombus formation, experimental data indicate that thrombin can induce an array of pro-atherogenic and plaque-destabilizing effects. Although thrombin plays a role in the pathophysiology of atherosclerosis progression and vascular calcification, the clinical evidence remains limited.
Using 64-slice coronary computed tomographic angiography, we assessed the presence and characteristics of CAD in patients (n = 295; median age 58 years) with stable chest pain. Coronary artery calcification was graded as absent (Agatston score 0), mild (Agatston score 1 to 100), moderate (Agatston score 101 to 400), and severe (Agatston score >400). Calibrated automated thrombography was used to assess endogenous thrombin potential in plasma in vitro. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation in vivo.
TATc plasma levels were substantially higher in patients with CAD versus patients without CAD (p = 0.004). Significant positive correlations were observed between steadily increasing TATc levels and the severity of CAD (r = 0.225, p < 0.001). In multinomial logistic regression models, after adjusting for established risk factors, TATc levels predicted the degree of coronary artery calcification: mild (odds ratio: 1.56, p = 0.006), moderate (odds ratio: 1.56, p = 0.007), and severe (odds ratio: 1.67, p = 0.002). Trends were comparable between the groups when stratified according to the degree of coronary luminal stenosis.
This study provides novel clinical evidence indicating a positive independent association between enhanced in vivo thrombin generation and the presence and severity of coronary atherosclerosis, which may suggest that thrombin plays a role in the pathophysiology of vascular calcification and atherosclerosis progression.
本研究旨在探讨血浆中凝血酶生成与疑似冠心病（CAD）患者计算机断层血管造影（CTA）定义的冠状动脉粥样硬化的存在和严重程度之间的关系。
除了在血栓形成中的关键作用外，实验数据表明凝血酶可以诱导一系列促动脉粥样硬化和斑块不稳定的作用。尽管凝血酶在动脉粥样硬化进展和血管钙化的病理生理学中发挥作用，但临床证据仍然有限。
使用 64 层冠状动脉 CT 血管造影术，我们评估了 295 名（中位年龄 58 岁）稳定型胸痛患者的 CAD 存在和特征。冠状动脉钙化程度分为无（Agatston 评分 0）、轻度（Agatston 评分 1-100）、中度（Agatston 评分 101-400）和重度（Agatston 评分>400）。使用校准的自动血栓生成术在体外评估血浆中的内源性凝血酶潜能。凝血酶-抗凝血酶复合物（TATc）水平作为体内凝血酶形成的标志物进行测量。
CAD 患者的 TATc 血浆水平明显高于无 CAD 患者（p = 0.004）。TATc 水平与 CAD 严重程度呈显著正相关（r = 0.225，p < 0.001）。在多变量逻辑回归模型中，在校正了已确立的危险因素后，TATc 水平预测了冠状动脉钙化的程度：轻度（比值比：1.56，p = 0.006）、中度（比值比：1.56，p = 0.007）和重度（比值比：1.67，p = 0.002）。根据冠状动脉管腔狭窄程度分层时，两组之间的趋势具有可比性。
本研究提供了新的临床证据，表明体内凝血酶生成增强与冠状动脉粥样硬化的存在和严重程度之间存在正相关独立关系，这可能表明凝血酶在血管钙化和动脉粥样硬化进展的病理生理学中发挥作用。
