Prognostic impact of aortic calcification index and ankle-arm blood pressure index in patients under hemodialysis.

The mortality rate is high in patients receiving hemodialysis (HD), atherosclerotic diseases being the major cause of death. As marker of clinical outcome, a prospective examination of atherosclerotic tests and atherosclerotic risk factors in patients receiving HD was performed. On April 2000, 84 patients receiving HD were followed up until April 2002. At entry to the study, several atherosclerotic tests, including ankle-arm blood pressure index (API), aortic calcification index (ACI), and atherosclerotic risk factors, were performed. In 36 patients with old thrombotic events, 26 had new thrombotic events. Of 48 patients without previous thrombotic events, 15 had new thrombotic events. During 2 years, 41 patients had new thrombotic events and 15 patients died due to thrombotic disorders. The HD durations were significantly longer in non-survivors than survivors and the body mass index was lower in non-survivors than survivors. There was a significant difference in the values of ACI and API between survivors and non-survivors, and between patients with and without thrombotic events. These findings suggest that the ACI and API have a prognostic value because they might predict the occurrence of thrombosis.

Effects of atorvastatin on serum lipids, lipoproteins, and hemostasis.

Serum levels of lipids and lipoproteins were examined in individuals with hyperlipidemia treated with atorvastatin or colestimide and in healthy volunteers. Modified low-density lipoprotein (LDL) was measured by its faster electrophoretic mobility and expressed as charge modification frequency (CMF). Serum levels of total cholesterol (t-chol), triglyceride (TG), very low-density lipoprotein (VLDL)-chol, low-density lipoprotein (LDL)-chol, and CMF were significantly higher in hyperlipidemia, but there was no significant difference in serum high-density lipoprotein (HDL)-chol levels between hyperlipidemic and healthy subjects. Treatment with atorvastatin resulted in significant decreases of serum t-chol, TG, and LDL-chol levels but not serum HDL-chol and VLDL-chol. Treatment with colestimide significantly reduced serum t-chol, HDL-chol, and LDL-chol levels but not those of TG and VLDL-chol. CMF was significantly reduced by treatment with atorvastatin but not by colestimide. Atorvastatin significantly reduced plasma levels of thrombomodulin, thrombin antithrombin complex (TAT) and tissue type plasminogen activator-plasminogen activator inhibitor-I complex. Colestimide moderately prolonged activated partial thromboplastin time and reduction of TAT. Based on its actions of lowering modified LDL and improving hemostatic abnormalities, we postulate that atorvastatin might inhibit the onset of ischemic diseases.

Effects of lipid abnormalities on arteriosclerosis and hemostatic markers in patients under hemodialysis.

Vascular events caused by arteriosclerosis are the major cause of death in patients under hemodialysis (HD). Arteriosclerosis is associated with lipoprotein abnormalities such as increased serum levels of low-density lipoprotein (LDL), especially of modified LDL (M-LDL) and oxidized LDL (Ox-LDL). We examined the relationship between markers of arteriosclerosis, hemostasis, and lipid metabolism in patients with chronic renal failure, hyperlipidemia, and healthy volunteers. In patients under HD, the serum levels of total cholesterol, LDL, and triglyceride (TG) were decreased, but the serum levels of M-LDL were increased compared to HL and healthy volunteers. In patients with CRF, the serum levels of Ox-LDL in patients under HD were lower than in those under continuous ambulatory peritoneal dialysis or conservative therapy. The plasma levels of antithrombin and protein C were significantly lower and the plasma levels of thrombomodulin were significantly higher in patients under HD compared to those under conservative therapy. These data show that patients under HD were more in hypercoagulable state than those under conservative therapy. Among patients under HD, only the plasma levels of von Willebrand factor were significantly increased in patients with more than 30 U/L of Ox-LDL compared to those with less than 30 U/L of Ox-LDL. There was no significant difference in the tests of arteriosclerosis among M-LDL values and Ox-LDL values. These findings suggest that abnormalities of lipid are not the main risk factor for arteriosclerosis disease in patients under HD.

Good or poor responses of hemostatic molecular markers in patients with hematopoietic disorders after treatment of disseminated intravascular coagulation.

Changes of hemostatic markers in 226 patients with disseminated intravascular coagulation (DIC) and hematopoietic disorders were examined after treatment of DIC. The changes in prothrombin time (PT) ratio, fibrinogen, fibrin and fibrinogen degradation products (FDP), antithrombin, and protein C, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), and soluble fibrin monomer complex (SFMC) in all patients with DIC were significant during the clinical course of DIC, but those of D-dimer, thrombomodulin (TM), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) were not. Activated partial thromboplastin time (aPTT) and PT were significantly longer in the poor response group than in good response group. Plasma levels of FDP, TAT, PPIC, SFMC, TM, and DIC score were significantly higher in poor response group than in good response. Protein C and antithrombin levels were significantly lower in poor response group than in good response group. The changes of PT ratio, fibrinogen, FDP, DIC score, antithrombin, plasmin inhibitor, and protein C were significant in the good response group, but these levels were not significant in the poor response group. The changes in plasma TAT and SFMC levels were significant in the good response group but were not in poor response group. The changes in D-dimer, TM, TF, or TFPI were not significant in both groups. These findings suggest that anticoagulant agents should be administered at levels below TAT 40 ng/mL or SFMC 300 microgram/mL in patients with DIC and hematopoietic disorders.

Expression of tissue factor and vascular endothelial growth factor is associated with angiogenesis in colorectal cancer.

We examined the expression of tissue factor (TF) and vascular endothelial growth factor (VEGF) and the microvessel density (MVD) in 100 patients with colorectal cancer, and we investigated the relationship of the expression of TF or VEGF with angiogenesis. TF antigen was positive in 57.0% of all specimens. Incidence of TF expression was 41.2%, 45.5%, 52.6%, 84.6%, and 81.3% in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. TF expression was correlated with the Dukes' classification (P = 0.01) and the clinical stage of colorectal cancer (P = 0.02). VEGF antigen was positive in 64.0% of all specimens. Incidence of VEGF expression was 41.2%, 57.6%, 73.7%, 84.6%, and 75.0% in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. VEGF expression was correlated with the Dukes' classification (P = 0.01) but showed a weak association with the clinical stage (P = 0.08). MVD was significantly associated with the depth of invasion (P = 0.01), lymph node metastasis (P = 0.001), and liver metastasis (P = 0.02). The mean values of MVD were 7.5 +/- 2.8, 10.1 +/- 5.7, 14.6 +/- 5.8, 13.5 +/- 3.9, and 15.9 +/- 4.2 in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. A close relationship between VEGF and MVD (P < 0.001) and a significant correlation between TF expression and MVD were observed (P = 0.02). TF-positive carcinomas presented high MVD and VEGF expression (P < 0.001) more frequently than did TF-negative tumors. These results suggest that involvement of TF in the process of metastasis and progression of colorectal cancer may depend on increased angiogenesis.