Segarra Alfons, Chacón Pilar, Martinez-Eyarre Cristina, Argelaguer Xavier, Vila Josefa, Ruiz Pilar, Fort Joan, Bartolomé Jorge, Camps Joaquin, Moliner Ernesto, Pelegrí Antoni, Marco Fernando, Olmos Antonio, Piera Lluis
Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
Bioquímica, Hospital Valle Hebrón, Barcelona, Spain.
J Am Soc Nephrol. 2001 Jun;12(6):1255-1263. doi: 10.1681/ASN.V1261255.
This study investigated the relationship between the circulating levels of the endothelial cell glycoproteins plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (TPA), and thrombomodulin (TM) and the major vascular risk factors described in dialysis patients. In addition, the role of these endothelial cell products as independent predictors of coronary artery disease (CAD) was analyzed. Levels of TM, TPA antigen (Ag), TPA activity, PAI-1 Ag, PAI-1 activity, TPA/PAI complexes, thrombin-antithrombin complexes, fibrinopeptide A, C-reactive protein (CRP), interleukin-1beta and tumor necrosis factor-alpha, lipids, apoproteins A1 and B, and albumin were measured in a group of 200 nondiabetic dialysis patients and 100 healthy matched volunteers. When compared with healthy controls, dialysis patients showed increased levels of CRP, TM, TPA, and PAI-1 and evidence of increased thrombin-dependent fibrin formation. Increased levels of active PAI-1 were associated to a great extent with major classic vascular risk factors and to a lesser extent with CRP and serum triglycerides. Forty-six patients (23%) had evidence of CAD. Variables associated with CAD in the univariate analysis included age, time on dialysis, male gender, number of packs of cigarettes per year, high BP, fibrinogen, apolipoprotein B, albumin, PAI-1 activity, CRP, thrombin-antithrombin complexes, and fibrinopeptide A. Logistic regression analysis found age, high-density lipoprotein cholesterol, gender, high BP, CRP, time on dialysis, and PAI-1 activity to be independent predictors of CAD. This model classified correctly 85% of patients as having CAD and showed adequate goodness of fit for all risk categories. Our data support a pathogenic link among activated inflammatory response, endothelial injury, and CAD in hemodialysis patients and suggest that assessment of circulating PAI-1 levels could be an additional tool to identify dialysis patients who are at risk for developing atheromatous cardiovascular disease.
本研究调查了内皮细胞糖蛋白纤溶酶原激活物抑制剂1型（PAI-1）、组织纤溶酶原激活物（TPA）和血栓调节蛋白（TM）的循环水平与透析患者中所述主要血管危险因素之间的关系。此外，还分析了这些内皮细胞产物作为冠状动脉疾病（CAD）独立预测因子的作用。在一组200例非糖尿病透析患者和100例健康匹配志愿者中，测量了TM、TPA抗原（Ag）、TPA活性、PAI-1 Ag、PAI-1活性、TPA/PAI复合物、凝血酶-抗凝血酶复合物、纤维蛋白肽A、C反应蛋白（CRP）、白细胞介素-1β和肿瘤坏死因子-α、脂质、载脂蛋白A1和B以及白蛋白的水平。与健康对照组相比，透析患者的CRP、TM、TPA和PAI-1水平升高，并有凝血酶依赖性纤维蛋白形成增加的证据。活性PAI-1水平升高在很大程度上与主要的经典血管危险因素相关，在较小程度上与CRP和血清甘油三酯相关。46例患者（23%）有CAD证据。单因素分析中与CAD相关的变量包括年龄、透析时间、男性性别、每年吸烟包数、高血压、纤维蛋白原、载脂蛋白B、白蛋白、PAI-1活性、CRP、凝血酶-抗凝血酶复合物和纤维蛋白肽A。逻辑回归分析发现年龄、高密度脂蛋白胆固醇、性别、高血压、CRP、透析时间和PAI-1活性是CAD的独立预测因子。该模型将85%的患者正确分类为患有CAD，并且对所有风险类别均显示出良好的拟合度。我们的数据支持血液透析患者中激活的炎症反应、内皮损伤和CAD之间的致病联系，并表明评估循环PAI-水平可能是识别有发生动脉粥样硬化性心血管疾病风险的透析患者的另一种工具。
