Hypercholesterolaemia is a risk factor for atherosclerosis and induces endothelial dysfunction. Endothelial dysfunction may increase vascular tone and arterial stiffness and as a consequence may decrease arterial distensibility (DC) and arterial compliance (CC). It is hypothesized that lipid-lowering therapy may enhance DC and CC. Therefore, the present study investigates the effect of lipid-lowering therapy with pravastatin on the haemodynamics, DC and CC of the elastic common carotid artery (CCA), and the muscular femoral (FA) and brachial (BA) arteries in patients with primary hypercholesterolaemia. After an 8-week placebo run-in period with a low-cholesterol diet, 19 patients with total cholesterol concentrations of between 6.5 and 9.0 mmol.l-1 and triglyceride concentrations < 4 mmol.l-1 entered a double-blind placebo controlled crossover study. Patients received pravastatin 40 mg o.d. or placebo, each for 8 weeks. Throughout the study the lipid-lowering diet was continued. With pravastatin, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides were decreased (total cholesterol 26%, LDL-C 35%, triglycerides 16%), while high-density lipoprotein cholesterol (HDL-C) was not changed. Other laboratory values remained within the normal range. Blood pressure, heart rate, cardiac function and systemic vascular resistance were not influenced by pravastatin. Compared to placebo, diameter, distensibility and compliance of all arteries were not statistically significantly changed with pravastatin. These data suggest that, in patients with mild to moderate primary hypercholesterolaemia, short-term lowering of plasma cholesterol does not alter the haemodynamics and vessel wall properties of large arteries.
The coagulation and fibrinolysis profile was evaluated in 40 patiens with newly diagnosed untreated colorectal carcinoma (24 males, 16 females; 29 patients without and 11 patients with metastases). Fibrinogen, von Willebrand factor antigen, FVIILC, thrombin-antithrombin III complex (TAT III), fibrin monomers (FM), plasminogen activator inhibitor-1 (PAI-1) and I-dimers were tested. None of the patients had clinical or laboratory evidence of serious hemorrhage or thrombosis. The results of global routine coagulation tests (aPTT, PT) were not significantly changed. Significant elevations were found for median fibrinogen, von Willebrand factor antigen, FVIILC, TAT III and D-dimers, compared with a healthy reference group. These results confirm earlier reports of an enhanced level of both coagulation and fibrinolysis markers in carcinoma patients and might be helpful in trying to understand the impact of several relatively new sensitive coagulation and fibrinolysis parameters in colorectal cancer. Moreover the position of the coagulation/fibrinolysis balance might be an explanation for the elevated incidence of thrombotic events in patiens with cancer.
Summary:Fifty-one patients with mild hypertension were evaluated in relation to the plasma concentrations of coagulation and fibrinolysis factors äs well äs for the aggregability of their platelets.In a considerable number of the patients (18/51), a significantly enhanced in vitro ADP aggregation was found. In the coagulation line significant increases could be demonstrated in fibrinogen, fibrin monomers and thrombin-antithrombin III. The fibrinolysis System showed significant increases for Ddimers, tissue plasminogen activator antigen and plasminogen activator Inhibitor, whereas the tissue plasminogen activator activity was significantly diminished. Remarkably, there seems to be a discrepancy between the (low) tissue plasminogen activator activity and the (higher) plasminogen activator antigen concentration.Alterations in the plasma concentrations of the investigated coagulation and fibrinolysis factors and in the aggregability of the platelets are indicative of an involvement of coagulation, fibrinolysis and platelets in hypertension, which can be considered äs partial risk factors for thrombophilia.
Nitrates decrease pulse pressure more than mean arterial pressure (MAP) and are advocated for the treatment of isolated systolic hypertension (ISH). Nitrates show drug tolerance during chronic treatment so an asymmetric dosing regimen may prevent loss of effect of nitrates. This study investigates the anti-hypertensive effect of isosorbide dinitrate (ISDN) given in a twice daily asymmetric dosing regimen in elderly patients with ISH.After a 6-week placebo run-in period, patients entered the double-blind study. Ten patients received placebo and 11 patients ISDN 20 mg b.i.d. for 8 weeks. This dose could be doubled once. Office systolic and diastolic blood pressures (SBP/DBP) and ambulatory BP were measured. Pulse pressure was calculated as SBP-DBP.Office pulse pressure was more reduced during ISDN
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