Juhan-Vague I, Pyke S D, Alessi M C, Jespersen J, Haverkate F, Thompson S G
Hematology Laboratory, CHU Timone, Marseille, France.
Circulation. 1996 Nov 1;94(9):2057-63. doi: 10.1161/01.cir.94.9.2057.
Disturbances of the fibrinolytic system that lead to decreased removal of fibrin deposits may be important risk factors for coronary thrombosis. There is as yet no consensus on the prognostic value of fibrinolytic parameters, which may be attributed in part to the choice of confounding variables controlled for.
The ECAT study is a prospective multicenter study of 3043 patients with angina pectoris followed for 2 years. Baseline measurements included 10 fibrinolytic variables. The results were analyzed in relation to the subsequent incidence of myocardial infarction or sudden coronary death. They are presented before and after adjustment for clusters of confounding variables that are markers of different mechanisms: insulin resistance (body mass index, triglyceride, and HDL cholesterol), inflammation (fibrinogen and C-reactive protein), and endothelial cell damage (von Willebrand factor). An increased incidence of events was associated with higher baseline concentrations of tissue plasminogen activator (TPA) antigen (P = .0002), plasminogen activator inhibitor-1 (PAI-1) activity (P = .02), and PAI-1 antigen (P = .001). The associations of PAI-1 activity and PAI-1 antigen with risk of events disappeared after adjustment for parameters reflecting insulin resistance but were not affected by other adjustments. TPA antigen was affected to a similar extent by adjustment for parameters reflecting insulin resistance. Inflammation, or endothelial cell damage, but the risk association disappeared only after combined adjustments.
The prognostic role of PAI-1 in predicting coronary events is related principally to insulin resistance, whereas that of TPA antigen could be explained only by its relationship with different mechanisms, including insulin resistance, inflammation and endothelial cell damage.
纤溶系统紊乱导致纤维蛋白沉积清除减少，可能是冠状动脉血栓形成的重要危险因素。关于纤溶参数的预后价值尚无共识，这可能部分归因于所控制的混杂变量的选择。
ECAT研究是一项对3043例心绞痛患者进行为期2年随访的前瞻性多中心研究。基线测量包括10个纤溶变量。分析结果与随后心肌梗死或心源性猝死发生率的关系。在对作为不同机制标志物的混杂变量簇进行调整前后呈现结果：胰岛素抵抗（体重指数、甘油三酯和高密度脂蛋白胆固醇）、炎症（纤维蛋白原和C反应蛋白）和内皮细胞损伤（血管性血友病因子）。事件发生率增加与组织纤溶酶原激活物（TPA）抗原基线浓度较高（P = 0.0002）、纤溶酶原激活物抑制剂-1（PAI-1）活性（P = 0.02）和PAI-1抗原（P = 0.001）相关。在对反映胰岛素抵抗的参数进行调整后，PAI-1活性和PAI-1抗原与事件风险的关联消失，但不受其他调整的影响。TPA抗原在对反映胰岛素抵抗、炎症或内皮细胞损伤的参数进行调整时受到类似程度的影响，但仅在联合调整后风险关联才消失。
PAI-1在预测冠状动脉事件中的预后作用主要与胰岛素抵抗有关，而TPA抗原的预后作用只能通过其与包括胰岛素抵抗、炎症和内皮细胞损伤在内的不同机制的关系来解释。
