RESUMO
Essential hypertension is often accompanied by abnormalities of the coagulation/fibrinolytic system, predisposing to a procoagulant state. The aim of the present study was to compare the effects of atenolol (beta1-blocker agent) and irbesartan (angiotensin II type 1 receptor antagonist) on plasma levels of hemostatic/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensives. Fifty-four patients were randomly assigned to atenolol 25 to 150 mg (26 patients) or irbesartan 75 to 300 mg (28 patients). The plasma levels of plasminogen activator inhibitor-1 antigen, thrombomodulin, tissue factor pathway inhibitor antigen, fibrinogen, and factor XII were determined before and after 6 months of therapy. Age, gender distribution, body mass index, lipid profile, and baseline values of the measured markers were similar in both groups. Baseline values for systolic and diastolic blood pressure, as well as the reduction after treatment, were not significantly different between the two groups. Treatment with irbesartan was associated with a significant decrease in the levels of all the parameters. Similar findings were observed in the atenolol group, except for factor XII and tissue factor pathway inhibitor levels, which were not significantly decreased in this group. The reduction, however, of fibrinogen, plasminogen activator inhibitor-1, and thrombomodulin was significantly greater in the irbesartan than in the atenolol group. In conclusion, the results indicated that, despite an equally controlled blood pressure, 6-month therapy with irbesartan was associated with a more favorable modification of hemostatic/fibrinolytic status than atenolol.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Atenolol/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Fibrinólise/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Tetrazóis/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Irbesartana , Lipídeos/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
This study was aimed at investigating haemostasis parameters in patients (pts) with arterial hypertension (AH) before any medical treatment and to correlate these findings with those in healthy normal Greek population 83 pts (48 m, 35 w) mean age 49.8 +/- 10.1 yrs, body mass index 23.4 +/- 1.5 with mild to moderate AH and 42 healthy volunteers matched for sex (24 m, 18 w), age 51.2 +/- 10.5 yrs and body mass index 22.8 +/- 1.46 were studied. Fibrinogen, vWF, plasminogen, ECLT, a2 antiplasmin, tPA-Ag, PAI-1 in all pts and in the control group were measured. Mean age and BMI did not significantly differ between the two groups. The hypertensive patients had significantly higher levels of fibrinogen (327.75 +/- 51.36 vs. 272.84 +/- 46.8 mg/dl), tPA-Ag (8.81 +/- 3.32 vs. 5.76 +/- 2.54 ng/ml) and PAI-1 (11.8 +/- 10.9 vs. 7.91 +/- 5.5 IU/ml), whereas a2 antiplasmin level was significantly lower (98.71 +/- 15.40 vs. 107.84 +/- 17.52%). No differences were found between hypertensives and normal subjects in vWF, plasminogen and ECLT. These preliminary data suggest that in pts with mild to moderate AH, before any medical treatment, there are significantly higher levels of fibrinogen, tPA-Ag and PAI-1 compared with normal volunteers, whereas there are significantly lower a antiplasmin levels. These findings indicate a disturbance in the haemostasis balance with hypercoagulability and fibrinolytic deficiency.
Assuntos
Transtornos da Coagulação Sanguínea/fisiopatologia , Hemostasia , Hipertensão/fisiopatologia , Adulto , Transtornos da Coagulação Sanguínea/sangue , Feminino , Fibrinogênio/metabolismo , Grécia/epidemiologia , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Plasminogênio/metabolismo , Inibidor 1 de Ativador de Plasminogênio/sangue , Ativador de Plasminogênio Tecidual/sangue , alfa 2-Antiplasmina/metabolismo , Fator de von Willebrand/metabolismoRESUMO
Essential hypertension is often accompanied by abnormalities of the coagulation/fibrinolytic system predisposing to a procoagulant state. The aim of the present study was to examine the comparative efficacy of the angiotensin II type 1 receptor antagonists eprosartan and losartan on plasma levels of hemostatic/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensive patients. A total of 86 patients whose hypertension was controlled by monotherapy with eprosartan 600 mg (45 patients) or losartan 100 mg (41 patients) were studied. The plasma levels of plasminogen activator inhibitor-1 (PAI-1) antigen, tissue plasminogen activator inhibitor (tPA) antigen, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI) antigen, and fibrinogen were determined before and after 6 months of therapy. Age, sex distribution, body mass index, lipid profile, systolic and diastolic blood pressure levels, and baseline values of the measured markers were similar in both groups. After 6 months of therapy, systolic blood pressure was significantly lower in patients treated with eprosartan, while no differences were observed with respect to diastolic blood pressure. Treatment with both drugs was associated with a significant decrease in PAI-1 antigen, TM, fibrinogen plasma levels and an increase in tPA antigen. The favorable modification of all the above parameters was significantly greater in the eprosartan than in the losartan group, while TFPI plasma levels were decreased to a similar extent with both drugs. In conclusion, the results of our study indicate that 6-month monotherapy with a new angiotensin II type 1 receptor blocker, eprosartan, is associated with a more favorable modification of hemostatic/fibrinolytic status than with losartan.
Assuntos
Acrilatos/uso terapêutico , Fibrinólise/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Losartan/uso terapêutico , Tiofenos/uso terapêutico , Acrilatos/farmacologia , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II , Esquema de Medicação , Feminino , Fibrinogênio/química , Fibrinogênio/efeitos dos fármacos , Fibrinólise/fisiologia , Seguimentos , Hemostasia/fisiologia , Humanos , Hipertensão/fisiopatologia , Imidazóis/farmacologia , Lipoproteínas/sangue , Losartan/farmacologia , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Receptor Tipo 1 de Angiotensina/uso terapêutico , Tiofenos/farmacologia , Trombomodulina/sangue , Trombomodulina/efeitos dos fármacos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/antagonistas & inibidores , Ativador de Plasminogênio Tecidual/sangue , Ativador de Plasminogênio Tecidual/efeitos dos fármacosRESUMO
AIM: Since conventional risk factors predict less than one half of future cardiovascular events, other factors that contribute to atherogenesis need to be evaluated. The aim of this study was to investigate whether clotting factors are associated with carotid artery disease. Furthermore, we tried to determine whether clotting factors could be used to predict the risk of cerebrovascular events in patients with internal carotid artery stenosis. METHODS: Twenty-six patients with high-grade (>70%) internal carotid artery stenosis and 43 age-matched controls were evaluated for atherogenic risk factors and hemostatic function. Laboratory tests included plasma assays of fibrinogen, tissue plasminogen activator (TPA), D-dimer, plasminogen activator inhibitor 1 (PAI-1), plasminogen and factor VII:c. Nineteen (72%) patients had history of stroke or transient ischemic attack, while the remaining 7 (28%) were asymptomatic. Statistical analysis was performed using multiple linear regression analysis. RESULTS: Carotid artery stenosis was associated with high levels of TPA (p<0.001), D-dimer (p=0.019) and PAI-1 (p<0.001). No statistically significant correlation was found between the presence of carotid artery disease and the levels of fibrinogen (p=0.28), plasminogen (p=0.96) or factor VII:c (p=0.19). As regards the clinical manifestations, none of the studied clotting factors was correlated with the history of cerebrovascular events in the patients with carotid stenosis. CONCLUSION: The results of this study show that the hemostatic system may play a role in the development of carotid artery atherosclerotic disease, while it does not seem to affect the development of symptoms in patients with carotid stenosis.
Assuntos
Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/fisiopatologia , Hemostasia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoAssuntos
Fator V/genética , Mutação Puntual , Fator V/metabolismo , Grécia , Humanos , Proteína C/metabolismoAssuntos
Fatores de Coagulação Sanguínea/metabolismo , Angina Microvascular/sangue , Resistência à Proteína C Ativada/sangue , Antitrombina III/metabolismo , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Fator VII/metabolismo , Fator VIII/metabolismo , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Plasminogênio/metabolismo , Inibidor 1 de Ativador de Plasminogênio/sangue , Proteína C/metabolismo , Proteína S/metabolismo , Fatores de Risco , Trombose/sangue , Ativador de Plasminogênio Tecidual/sangue , Fator de von Willebrand/metabolismoRESUMO
BACKGROUND AND AIM: Postprandial glycaemia and lipaemia are known risk factors for atherosclerosis in type 2 diabetes. Coagulation activation in the postprandial state also contributes to acceleration of atherosclerosis. Nateglinide is effective in reducing postprandial glycaemia. Its effect on glycaemia may also be beneficial in postprandial lipaemia and coagulation. The aim of this study was to examine the potential effect of a single dose of nateglinide on postprandial triglyceridaemia, coagulation, and fibrinolysis in patients with type 2 diabetes. METHODS AND RESULTS: Ten subjects with type 2 diabetes, treated with diet alone were recruited in a crossover randomized study. In the morning, after a 12- to 14-h fast, each subject received a standard mixed meal (total energy 783 kcal), preceded by one tablet of 120 mg nateglinide or placebo. Venous blood samples were drawn prior to meal consumption and 6h afterwards for the measurement of plasma glucose, insulin, and C-peptide, lipids, coagulation, and fibrinolysis factors. As expected, there was a significant reduction in postprandial glycaemia after nateglinide administration compared to placebo (P<0.001). Plasma insulin levels were significantly higher after nateglinide than after placebo (P=0.002). Nateglinide administration resulted in a lower overall postprandial reduction of tissue-plasminogen activator than placebo (-2.9+/-1.3 vs. -8.3+/-3.7 ng/ml h, P=0.003). In addition, a significant reduction of postprandial plasminogen activator inhibitor-1 was observed in comparison with the baseline values after nateglinide (P=0.001), although the overall response was not significantly different after nateglinide and placebo (P=0.31). Plasma concentrations of C-peptide, lipids and the remaining coagulation parameters studied were not different between nateglinide and placebo. CONCLUSIONS: Acute nateglinide administration improves postprandial glycaemia and fibrinolytic activity in patients with type 2 diabetes. This combined effect, if confirmed by a long-treatment study, might reduce cardiovascular risk in type 2 diabetes.
Assuntos
Cicloexanos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Lipídeos/sangue , Fenilalanina/análogos & derivados , Adulto , Idoso , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Estudos Cross-Over , Cicloexanos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Feminino , Fibrinólise/efeitos dos fármacos , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Metabolismo/efeitos dos fármacos , Pessoa de Meia-Idade , Nateglinida , Fenilalanina/farmacologia , Fenilalanina/uso terapêutico , Período Pós-Prandial/efeitos dos fármacos , Período Pós-Prandial/fisiologia , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Previous data indicate that even mild postprandial hyperglycaemia in diabetic subjects, who are concerned to be in good control, activates haemostasis. The aim of this study was to investigate the effect of the oral administration of 5 mg glibenclamide on postprandial activation of coagulation in type 2 diabetics. METHODS AND RESULTS: We designed a placebo controlled, randomised study. After an overnight fast, each subject (n = 16, age 50-68 yr.) underwent a standard test meal (600 Kcal: carbohydrates 40%, lipids 50%, proteins 10%) preceded by one tablet of glibenclamide (5 mg) or placebo. The two tests were performed randomly, with an interval of 7 days. Blood samples were collected at baseline and 2 and 4 hours after the meal to measure the concentrations of glucose, insulin, c-peptide, triglycerides as well as of d-dimers, fibrinogen, F1.2 and TAT. The postprandial levels of TAT, fibrinogen, F1.2, d-dimers, insulin, glucose and triglycerides were significantly higher compared to baseline values. CONCLUSIONS: The postprandial levels of glucose, triglycerides, fibrinogen, F1.2, TAT and d-dimers were lower after glibenclamide administration as compared to placebo, while the concentrations of insulin and c-peptide were higher. Thus, acute administration of glibenclamide reduces the postprandial activation of coagulation.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Glibureto/farmacologia , Hipoglicemiantes/farmacologia , Administração Oral , Idoso , Análise de Variância , Área Sob a Curva , Estudos Cross-Over , Feminino , Glibureto/administração & dosagem , Hemostasia/efeitos dos fármacos , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Período Pós-PrandialRESUMO
Increased sympathetic activity seems to play an important role in the pathogenesis and development of complications of atherosclerotic origin in patients with essential hypertension (EH). The aim of this study was to evaluate the effect of a new antihypertensive agent, moxonidine (M), on microalbuminuria (urine albumin excretion, UAE), plasma thrombomodulin (TM), and tissue plasminogen activator inhibitor (PAI-1) in patients with mild to moderate EH associated with increased UAE. Fifty-eight patients (32 M, 26 F) with EH and microalbuminuria, with a mean age of 56.6 +/- 8.2 years and a body mass index (BMI) of 23.8 +/- 3.1 kg/m2 who responded to M therapy (0.3-0.4 mg/daily) were studied before and after their blood pressure control. The 24-hour urine albumin excretion (RIA method), as well as TM and PAI-1 plasma levels (ELISA method), were determined before and 6 months after the initiation of treatment under moxonidine therapy. At the end of the 6-month period, all patients remained normotensive. The 24-hour urine albumin excretion had decreased to 24.5 +/- 6.4 vs. 32.3 +/- 7.2 ug/min before therapy (P < 0.001). The plasma TM levels had decreased to 44.0 +/- 7 vs. 51.0 +/- 9 ng/mL before therapy (P < 0.01), and PAI-1 levels had also decreased to 11.5 +/- 4.5 vs. 15.8 +/- 8 IU/mL before therapy (P < 0.05). The results of our study suggest that in hypertensive patients with microalbuminuria, moxonidine, an imidazoline I1-receptor agonist, a new centrally acting antihypertensive agent, significantly reduces urine albumin excretion as well as thrombomodulin and PAI-1 levels. These preliminary findings demonstrate a favorable effect on renal function and endothelial homeostatic mechanisms (maintenance of haemostatic balance).
Assuntos
Albuminúria/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Imidazóis/uso terapêutico , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Trombomodulina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. METHODS: The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D-dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). RESULTS: Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =. 012), tPA antigen (P =.0001), fibrinogen (P =.0002), D-dimer (P =. 0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. CONCLUSIONS: Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension.