The Study Of Plasma Level Of Tissue Factor Pathway Inhibitor And V264M Polymorphism Of Its Gene In The Patients With Acute Coronary Syndrome

Background: Thrombus formation on disrupted and ulcer atherosclerotic lesions plays a fundamental role in the onset of acute coronary syndrome(ACS). Recent studies have showed tissue factor(TF) plays a major role in arterial thrombosis. TF is the main initiator of the coagulation cascade. Tissue factor pathway inhibitor(TFPI), as a natural anticoagulant, is thought to inhibit TF-induced activation of the coagulation cascade. In addition, TFPI decreases plasma levels of inflammatory chemotaxin and inhibits the proliferation of vascular wall cells by inducing apoptosis. Therefore, TFPI plays an important role in the atherosclerosis and thrombosis. Coronary artery disease is caused by multifactor. To explore new risk factors of coronary artery disease will contribute to understand deeply its mechanism. ACS is thought to the severe state of a series of myocardial ischemia spectrum according to its high risk and mortality, so it is very significant to study the involved risk factors of ACS.Objectives: The aim of this study was designed to examine the plasma level of total TFPI(T.TFPI) in patients with ACS and the V264M polymorphism of the TFPI gene exon IX. The relationship between the plasma level of T.TFPI and ACS was analysed. We also sought to evaluate the predicting value of plasma level of T.TFPI for risk stratification and prognosis in patients with ACS. Meanwhile, therelationships between the V264M polymorphism of the TFPI gene exon DC in Han nationality of Chinese in Henan area and plasma level of T.TFPI and ACS were analyzed.Methods: We selected fifty-three in-patients with ACS in the cardiovascular department of the first affiliated hospital of zhengzhou university from February 2003 to August 2003. They were divided into two groups: twenty-seven ST-segment elevated ACS (STEACS) patients and twenty-six non-ST-segment elevated ACS (NSTEACS) patients, according to the ST-segment changes on the onset of ACS. All patients with ACS were diagnosed by electrocardiogram and cardiac enzyme, of which, 19 documented also by coronary angiography. In addition, there were fifty-three healthy subjects for physical examination served as a control group. All of the studied subjects were Han nationality of Chinese in Henan area. 4ml venous blood of the patients with ACS in hospital was taken from the antecubital vein within 24h and before intravenous heparin; while that of the control subjects in out-patient before 8AM on an empty stomach. Those blood was collected into 3.8% trisodium citrate anticoagulant solution in the proportion of 9 volumes of blood to 1 volume of anticoagulant solution. Plasma level of T.TFPI was determined by enzyme linked immunosorbent assay (ELISA) and compared in each group. Meanwhile, fifty-three patients with ACS were divided into >137.47ng/ml group and <137.47ng/ml group according to the plasma level of T.TFPI. The incidences of major adverse cardiovascular events (MACE), including recurrent ischemic angina, nonfatal myocardial infarction and cardiac sudden death, were observed in each group during in-hospital and follow-up period (six months). The V264M polymorphism of the TFPI was also examined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) technology in 53 patients with ACS and 53 control subjects.Results: (1) The plasma level of T.TFPI was significantly higher in the ACS group than in the control group (137.47+51.93ng/ml vs 78.18+9.49ng/ml, P<0.001), and was substantially higher in the STEACS group and in the NSTEACS group than in the control group(177.95+33.02 vs 78.18+9.49 and 95.44+29.45 vs 78.18+9.49, P< 0.001, respectively). The plasma level of T.TFPI increased in the STEACS group more than in the NSTEACS group(177.95+33.02 vs 95.44+29.45, P<0.05). (2) The patients with NSTEACS and STEACS respectively accounted for 88.9% and 11.1% in T.TFPK137.47ng/ml group. In contrary, the patients with NSTEACS and STEACS accounted for 7.7% and 92.3% in T.TFPI> 137.47ng/ml group respectively. There was a significant difference between high-level grou...