老年急性冠状动脉综合征早期血浆组织因子及其途径抑制物2的变化规律

Changes of plasma tissue factor and tissue factor pathway inhibitor 2 levels in elderly patients with acute coronary syndrome

目的观察老年急性冠状动脉综合征(ACS)患者在病程早期的血浆组织因子(TF)、基质金属蛋白酶(MMP)-1水平,以及组织因子途径抑制物(TFPI)-2的变化规律,探讨TFPI-2在ACS发病机制及病情监测中的意义。方法连续入选2008年3月—2009年3月在复旦大学附属华山、华东医院住院,年龄≥60岁的患者,根据临床表现、冠状动脉造影检查结果分别入选ACS组及稳定型心绞痛(SAP)组。冠状动脉造影检查正常的老年健康者入选正常组。ACS组分别于入院24h内及发病后2、4周采集外周静脉血,SAP、正常组于入院24h内采集外周静脉血,采用酶联免疫吸附试验检测血浆TF、TFPI-2及MMP-1水平,计算TF/TFPI-2比值。结果共纳入176例患者,ACS组96例,SAP组50例及正常组30例。各组间年龄,性别构成,高血压、吸烟、糖尿病构成比,低密度脂蛋白胆固醇、三酰甘油水平,他汀类药物及血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂使用率的差异均无统计学意义(P值均>0.05),ACS组的高密度脂蛋白胆固醇、左心室射血分数(LVEF)均显著低于SAP组和正常组(P值均<0.05),而血肌酐(sCr)、超敏C反应蛋白(hsCRP)均显著高于SAP组和正常组(P值均<0.05)。发病24h时,与SAP组和正常组相比,ACS组的TFPI-2水平显著降低(P值均<0.05),而TF、MMP-1水平及TF/TFPI-2比值均显著升高(P值均<0.05)。ACS组中,TF水平随病程的延长而逐步降低(P值均<0.05),TFPI-2水平随病程的延长而先升高,然后降低(P值均<0.05)。Logistic多元回归分析显示,血浆TFPI-2和LVEF下降以及血浆TF、MMP-1和hsCRP水平升高与ACS的发病相关(P值均<0.05)。结论老年ACS患者在病程早期的血浆TFPI-2水平较低,而TF、MMP-1水平较高,提示TFPI-2的分泌不足可能参与ACS的发病。

Objective To measure the levels of plasma tissue factor （TF）, matrix metalloproteinase 1 （MMP-1） and tissue factor pathway inhibitor-2 （TFPI-2） in the early stage of acute coronary syndrome （ACS） in elderly patients, and to investigate the role of TFPI-2 in the process of ACS and possibility of TFPI-2 as a early plasma markers for ACS. Methods A consecutive series of in-hospital patients （age≥60 years old） in Huashan Hospital and Huadong Hospital between March 2008 and March 2009 were enrolled in this study. The patients were diagnosed as ACS and stable angina pectoris （SAP） according to clinical manifestation and coronary angiogram （CAG）. The patients with normal CAG results were set as control group. Venous blood samples were obtained on admission, and at 2 and 4 weeks after symptom onset. Plasma concentrations of TF, TFPI-2 and MMP-1 were measured by enzyme-linked immunosorbent assay （ELISA） and the ratio of TF to TFPI-2 was calculated. Results A total of 176 patients were enrolled in the study （96 with ACS, 50 with SAP and 30 with normal coronary arteries）. There were no statistical differences in age, gender, hypertension, smoking, diabetes, low density lipoprotein, triglyceride or medication including statins and angiotensin converting enzyme inhibitors （ACEI）/ angiotensin receptor blocker （ARB） among three groups （all P〈0. 05）. High density lipoprotein and left ventricular ejection fraction （LVEF） in ACS group were significantly lower than those in SAP and control groups, while serum creatinine and high sensitive C reactive protein （hsORP） in ACS group were significantly higher than those in SAP and control groups （P〈0.05）. On admission, TF and MMP-1 levels and the ratio of TF to TFPI-2 were significantly increased while TFPI-2 was significantly decreased in ACS group as compared with SAP and control groups （all P〈0.05）. In the ACS group, TF was decreased and TFPI-2 was elevated gradually and then declined as the disease developed （all P〈0.05）. Multivariate logistic regression analysis revealed that a low level of TFPI-2 on admission was an independent factor related to the development of ACS, along with low LVEF, and high TF, MMP-1 and hsCRP levels （all P〈0.05）. Conclusion In the early stage of ACS, elderly patients have low level of TFPI-2 and high levels of TF and MMP-1, implying that the lack of TFPI-2 may be related to ACS.