Efficacy of olmesartan therapy on fibrinolytic capacity in patients with hypertension.
ABSTRACT The efficacy of olmesartan on fibrinolytic capacity has not been studied yet. Therefore, the aim of the present study was to investigate the efficacy of olmesartan on hemostatic/fibrinolytic status by measuring plasma level of plasminogen activator inhibitor-1 (PAI-1) and soluble thrombomodulin levels in patients with hypertension. Forty-two consecutive, newly diagnosed (25 women and 17 men with a mean age of 48 ± 8 years) patients with untreated essential hypertension were included in the study. Olmesartan medoxomil (20 mg/day) was started and the patients were followed up for 6 months. Baseline biochemical variables, thrombomodulin, and PAI-1 levels were compared with the levels of these variables measured at the end of the 6-month follow-up period. After 6 months of treatment with olmesartan medoxomil, there was a significant reduction in systolic and diastolic blood pressure (from 159.5 ± 10.9 to 134.6 ± 12.7 mmHg and from 98.0 ± 6.3 to 83.9 ± 7.0 mmHg, respectively). Mean plasma PAI-1 and thrombomodulin levels were also significantly decreased (59.73 ± 41.91 vs. 48.60 ± 33.65 ng/ml, P = 0.001 and 8.09 ± 2.29 vs. 6.92 ± 1.42 μg/l, P < 0.001, respectively). Olmesartan medoxomil decreased plasma PAI-1 and thrombomodulin levels after 6 months of therapy, indicating a favorable effect on fibrinolytic capacity in patients with essential hypertension.
- The American Journal of Medicine 11/1997; 103(4):331-2. · 5.30 Impact Factor
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ABSTRACT: The greater than normal cardiovascular risk of hypertensive patients could be partly due to an impairment of hemostatic balance found in such individuals. To examine the relationship between hemostatic variables and blood pressures in 1950 apparently healthy male participants in the prospective cardiovascular Münster study aged 40-65 years. Blood pressure and other variables were determined, including fibrinogen level, coagulation factor VII clotting activity, protein C level, antithrombin III level, plasminogen activator inhibitor-1 level, euglobulin fibrinolytic activity, and von Willebrand factor level. Age-adjusted mean values of coagulation factor VII clotting activity, plasminogen activator inhibitor-1 level, antithrombin III level, and protein C level in hypertensives and borderline hypertensives were significantly higher than those in normotensive men (e.g. for hypertensive versus normotensive men, coagulation factor VII clotting factor activity 111.5 versus 106.1%, plasminogen activator inhibitor-1 level 5.05 versus 3.22 arbitrary units/ml, and protein C level 111.1 versus 107.0%, P < 0.05-0.01). For most of the hemostatic variables we found positive bivariate correlations to blood pressure (P < or = 0.05). Exceptions were von Willebrand factor level (no correlation to blood pressure), and euglobulin fibrinolytic activity (a negative correlation to systolic blood pressure and no correlation to diastolic blood pressure). Significance persisted in the multiple logistic regression analysis with the exception of the relationships between systolic and diastolic blood pressures and fibrinogen level as well as euglobin fibrinolytic activity after adjustment for age. After adjustment for age and body mass index significance for relationships between systolic blood pressure and coagulation factor VII clotting activity as well as protein C level was also lost. We conclude that the greater than normal cardiovascular risk of hypertensive patients is partly due to an imbalance in hemostasis.Journal of Hypertension 08/1998; 16(7):917-23. · 4.22 Impact Factor
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ABSTRACT: Background: Thrombomodulin (TM) is a membrane glycoprotein in the vascular endothelium. It may be cleaved from endothelial cells and released into the circulation. The plasma TM level depends on the integrity of the endothelium and the clearance of the molecule. The physiological role of soluble TM forms is still unclear. The clinical significance of elevated levels of TM in various pathologic conditions is not well established yet. To analyze variations of plasma TM level in different clinical situations, its concentrations in patients with three groups of diseases were measured and compared with those in healthy subjects. Methods: Plasma samples from 23 patients at risk for development of vascular complications [essential hypertension (EH), stages 1 and 2], 31 patients with inflammatory bowel diseases [Crohn's disease (IBD), mostly in the active stage], and 19 patients with malignant tumors [gastric carcinoma (NEO)], were analyzed for soluble TM with an enzyme immunoassay kit. Results: In the group of patients with the early stages of EH and with non-active IBD, no significant changes were found in comparison to the healthy subjects. In the patients with active IBD and mainly with NEO, soluble TM was significantly increased (P<0.05 and P<0.001, respectively). Conclusions: Our TM levels failed to demonstrate increased endothelial damage in the early stage of EH. This suggests that TM is released into the plasma only by true endothelial cell damage during the development of vascular complications. Probably a certain degree of endothelial injury is necessary for an increase in plasma. In the active stage of IBD and in NEO, soluble TM appears to be derived not only from injured endothelial cells, but may also be proteolytically cleaved from membrane TM by proteases. There may also be increased synthesis of TM in activated and/or transformed cells.European Journal of Internal Medicine 04/2000; 11(2):79-84. · 2.30 Impact Factor