RESUMEN
AIMS: To compare the effects of losartan and amlodipine on myocardial structure and function in hypertensive patients with Type 2 diabetes and left ventricular hypertrophy. METHODS: After a 4-week placebo period, patients were randomized to losartan 50 mg (n = 90) or amlodipine 5 mg (n = 91) for 12 months, with a doubling of the dose in patients who did not respond after 4 weeks. Blood pressure was measured in the clinic every month, while conventional echocardiography and acoustic densitometry (integrated backscatter analysis) were performed at the end of the placebo period and after 12 months of treatment. RESULTS: Both drugs reduced systolic/diastolic blood pressure to a comparable extent. Losartan significantly reduced left ventricular mass index (-19%, P < 0.001), interventricular septal thickness (-16.6%, P < 0.01) and left ventricular posterior wall thickness in diastole (-13.7%, P < 0.01). Amlodipine also decreased such measurements (-10%, P < 0.01 for left ventricular mass index, -9.3%, P < 0.05 for interventricular septal thickness in diastole and -10.1%, P < 0.05 for posterior wall thickness in diastole), but to a lesser extent than losartan. Both drugs significantly increased the ratio of peak filling velocity at early diastole to that at atrial contraction (E/A ratio) and decreased isovolumetric relaxation time: +13.7% and -8.5% with losartan,(both P < 0.01), and +7.9% and -4.9%, with amlopidine (both P < 0.05). Losartan, but not amlodipine, significantly reduced the relative integrated backscatter compared to baseline of the intraventricular septum (-10%, P < 0.01), and of the left ventricular posterior wall (-12%, P < 0.01), while increasing the cyclic variation of integrated backscatter of both the intraventricular septum (+35%, P < 0.001) and the left ventricular posterior wall (+32%, P < 0.001). CONCLUSIONS: Losartan provided a greater attenuation of left ventricular hypertrophy than amlodipine, seemingly as a result of a greater reduction of myocardial fibrosis.
Asunto(s)
Amlodipino/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Angiopatías Diabéticas/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/prevención & control , Losartán/uso terapéutico , Disfunción Ventricular Izquierda/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/fisiopatología , Diástole/efectos de los fármacos , Ecocardiografía , Femenino , Fibrosis/tratamiento farmacológico , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/etiología , Masculino , Persona de Mediana Edad , Miocardio/patología , Estudios Prospectivos , Resultado del Tratamiento , Disfunción Ventricular Izquierda/etiologíaRESUMEN
AIM: To evaluate the effect of aliskiren compared to amlodipine on QT duration and dispersion in hypertensive patients with type 2 diabetes. METHODS: A total of 170 outpatients aged 50-75 years with mild to moderate hypertension (SBP >130 and <180 mmHg and DBP >80 and <100 mmHg) and type 2 diabetes were randomly treated with aliskiren 300 mg or amlodipine 10 mg, both given once daily for 24 weeks, according to a prospective, open label, blinded-end point, parallel group design. At the end of the placebo run-in, and after 12, and 24 weeks of treatment blood pressure (BP) measurements (by mercury sphygmomanometer, Korotkoff I and V), plasma biochemistry and a standard 12-lead surface ECG were evaluated. RESULTS: Both aliskiren and amlodipine significantly reduced systolic blood pressure (SBP)/diastolic blood pressure (DBP) values (-27.2/-14.3 mmHg, p < 0.001 vs. placebo and -27.8/-14.2 mmHg, p < 0.001 vs. placebo, respectively), with no statistical difference between the two drugs. Aliskiren, but not amlodipine, significantly reduced maximum QT interval (QTmax) (-14 ms at 12 weeks and -17 ms at 24 weeks, both p < 0.05 vs. placebo) and corrected QT max (QTc max) (-26 ms and -31 ms, p < 0.01) as well as the dispersion of both QT (-11 ms and -13 ms, p < 0.01) and QTc (-18 ms and -19 ms, p < 0.01). CONCLUSIONS: Despite similar BP lowering effect, aliskiren, but not amlodipine, reduced QT duration and dispersion, which might be related to the ability of aliskiren to interfere with mechanisms underlying myocardial electrical instability in the heart of diabetic hypertensive patients.
Asunto(s)
Amidas/farmacología , Amlodipino/farmacología , Antihipertensivos/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Fumaratos/farmacología , Sistema de Conducción Cardíaco/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Síndrome de QT Prolongado/tratamiento farmacológico , Anciano , Amidas/administración & dosificación , Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/complicaciones , Angiopatías Diabéticas/fisiopatología , Electrocardiografía , Femenino , Fumaratos/administración & dosificación , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Síndrome de QT Prolongado/etiología , Síndrome de QT Prolongado/fisiopatología , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The aim of this study was to compare the effect of aliskiren and losartan on fibrinolysis and insulin sensitivity (IS) in hypertensive patients with metabolic syndrome. After 2-week placebo period, 76 outpatients with mild to moderate hypertension and metabolic syndrome were randomized to aliskiren 300 mg od or losartan 100 mg od for 12 weeks. Clinic blood pressure (BP), plasma PAI-1 antigen, and tPA activity were evaluated after 2, 4, 8, and 12 weeks of treatment. At the end of each treatment period patients performed an euglycemic hyperinsulinemic clamp and IS was assessed by glucose infusion rate (GIR). Both aliskiren and losartan induced a significant and similar SBP/DBP reduction (-15.6/10.7 mmHg and -15.5/10.5 mmHg, p<0.001 vs. baseline, respectively). Both drugs decreased PAI-1 antigen and activity after 2 weeks of treatment; subsequently, only the decreasing effect of aliskiren was sustained throughout the 12 weeks [-7.5 ng/ml (-31%) p<0.05 vs. baseline], while with losartan PAI-1 increased at week 12 [+3.6 ng/ml (+15%), p<0.05 vs. baseline and p<0.01 vs. aliskiren)]. The tPA activity showed no significant change with aliskiren and a decrease with losartan [-0.04 IU/ml (-8%), p<0.05 vs. baseline and p<0.01 vs. aliskiren]. Aliskiren significantly increased GIR [+1.4 mg/min/kg (+28%), p<0.01 vs. baseline] while losartan did not change it [+0.2 mg/min/kg (+4%), NS vs. baseline, p<0.05 vs. aliskiren)]. These results indicated that in this type of patients, despite similar BP reduction, aliskiren improved the fibrinolytic balance as well as IS, while losartan worsened the fibrinolytic balance and did not affect IS. The clinical relevance of these different effects remains to be clarified.
Asunto(s)
Amidas/uso terapéutico , Antihipertensivos/uso terapéutico , Fibrinólisis/efectos de los fármacos , Fumaratos/uso terapéutico , Hipertensión/tratamiento farmacológico , Insulina/metabolismo , Losartán/uso terapéutico , Síndrome Metabólico/metabolismo , Adolescente , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Hipertensión/metabolismo , Hipertensión/fisiopatología , Masculino , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Adulto JovenRESUMEN
The aim of this study was to compare the effect of telmisartan and eprosartan on insulin sensitivity in overweight hypertensive patients. Fifty overweight (BMI > or = 25 and <30 kg/m (2)) outpatients, aged 41-65 years, with mild to moderate hypertension [systolic blood pressure (SBP) >140 and diastolic blood pressure (DBP) > or = 90 and < or = 110 mmHg], after a 4-week placebo period, were randomized to receive telmisartan 80 mg or eprosartan 600 mg for 8 weeks. Following another 4-week placebo period, patients were crossed to the alternative regimen for further 8 weeks. At the end of each placebo and active treatment period, blood pressure (BP), insulin sensitivity (by euglycemic hyperinsulinemic clamp), fasting plasma glucose (FPG), insulin (FPI), total cholesterol (TC), LDL-C, HDL-C, and triglycerides (Tg) were evaluated. Insulin sensitivity was expressed as the amount of glucose infused during the last 30 min (glucose infusion rate, GIR) in micromol/min/kg. Both telmisartan and eprosartan significantly reduced SBP/DBP values (by a mean of 19.4/13.3 mmHg and 17.9/12.1 mmHg respectively, all p<0.001 vs. placebo), with no significant difference between the two treatments. GIR was significantly increased by telmisartan (2.25+/-0.61 micromol/min/kg, p<0.05 vs. placebo) but not by eprosartan (0.25+/-0.14 micromol/min/kg, p=ns), the difference between the two drugs being statistically significant (p<0.02). No change in FPG, FPI, HDL-C, and Tg was observed with either treatment. Telmisartan significantly reduced TC (-9.9 mg/dl, -5%, p<0.04 vs. placebo) and LDL-C (-8.8 mg/dl, -7%, p<0.03 vs. placebo), whereas eprosartan did not influence them. These findings indicate a superiority regarding an improvement of insulin sensitivity and plasma lipid profile in overweight hypertensives by telmisartan as compared to eprosartan, possibly related to the selective stimulating PPAR-gamma property of telmisartan.
Asunto(s)
Acrilatos/uso terapéutico , Bencimidazoles/uso terapéutico , Benzoatos/uso terapéutico , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Imidazoles/uso terapéutico , Insulina/metabolismo , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Tiofenos/uso terapéutico , Adulto , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Glucemia , Femenino , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Sobrepeso/sangre , Sobrepeso/fisiopatología , TelmisartánRESUMEN
The aim of this study was to assess the effect of valsartan addition to amlodipine on ankle foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. After a 4-week placebo period, 80 grade 1-2 hypertensive patients (diastolic blood pressure (DBP)>90 mm Hg and <110 systolic blood pressure (SBP)>140 mm Hg) were randomized to amlodipine 10 mg or valsartan 160 mg or amlodipine 10 mg plus valsartan 160 mg for 6 weeks according to an open-label, blinded end point, crossover design. At the end of the placebo period and of each treatment period, blood pressure, AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed connecting the subcutaneous pretibial interstitial environment with a water manometer. Both amlodipine and valsartan monotherapy significantly reduced SBP (-16.9 and -14.5 mm Hg, respectively, P<0.01 vs baseline), and DBP (-12.9 and -10.2 mm Hg, respectively, P<0.01 vs baseline) but the reduction was greater with the combination (-22.9 mm Hg for SBP, P<0.01 vs monotherapy; -16.8 mm Hg for DBP, P<0.01 vs monotherapy). Amlodipine monotherapy significantly increased both AFV (+23%, P<0.01 vs baseline) and PSTP (+75.5%, P<0.001 vs baseline) whereas valsartan monotherapy did not influence them. As compared to amlodipine alone, the combination produced a less marked increase in AFV (+6.8%, P<0.01 vs amlodipine) and PSTP (+23.2%, P<0.001 vs amlodipine). Ankle oedema was clinically evident in 24 patients with amlodipine and in six patients with the combination. These results suggest that angiotensin receptor blockers partially counteract the microcirculatory changes responsible for calcium channel blockers induced oedema formation.
Asunto(s)
Amlodipino/uso terapéutico , Presión Sanguínea , Edema/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Tetrazoles/uso terapéutico , Valina/análogos & derivados , Adulto , Factores de Edad , Anciano , Tobillo , Estudios Cruzados , Quimioterapia Combinada , Edema/complicaciones , Edema/fisiopatología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Placebos , Estudios Prospectivos , Método Simple Ciego , Resultado del Tratamiento , Valina/uso terapéutico , ValsartánRESUMEN
The aim of this study was to compare the effects of telmisartan/hydrochlorothiazide (HCTZ) vs lisinopril/HCTZ combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. A total of 160 patients, 76 men and 84 women, aged 61-75 years, with sitting diastolic blood pressure (DBP)>90 mmHg and <110 mmHg and systolic blood pressure (SBP)>140 mmHg were randomized to receive temisartan 80 mg/HCTZ 12.5 mg o.d. or lisinopril 20 mg/HCTZ 12.5 mg o.d. for 24 weeks, according to a prospective, open-label, blinded end point, parallel-group design. At the end of a 2-week wash-out period and after 12 and 24 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed and cognitive function was evaluated through six different tests (verbal fluency, Boston naming test, word-list memory, word-list recall, word-list recognition and Trails B). Both treatments significantly reduced ambulatory BP. However, the telmisartan/HCTZ combination produced a greater reduction in 24-h, day-time and night time ABPM values. Lisinopril/HCTZ did not induce significant changes in any of the cognitive function test scores at any time of the study, whereas at both 12 and 24 weeks telmisartan/HCTZ significantly improved the word-list memory score (+17.1 and +15.7%, respectively, P<0.05 vs baseline), the word-list recall score (+13.5 and +16.9%, P<0.05) and the Trails B score (-33 and -30.5%, P<0.05). These results suggest that in elderly hypertensive patients treatment with telmisartan/HCTZ produces a slightly greater reduction in ambulatory BP than lisinopril/HCTZ combination and, unlike this latter, improves some of the components of cognitive function, particularly episodic memory and visuospatial abilities.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Bencimidazoles/uso terapéutico , Benzoatos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Cognición/efectos de los fármacos , Hidroclorotiazida/uso terapéutico , Hipertensión/tratamiento farmacológico , Lisinopril/uso terapéutico , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Anciano , Análisis de Varianza , Determinación de la Presión Sanguínea , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estadísticas no Paramétricas , Telmisartán , Resultado del TratamientoRESUMEN
This study was undertaken to evaluate the effects on blood pressure of hydrochlorothiazide (HCTZ) 12.5 mg added to valsartan 160 mg or to olmesartan 20 mg in hypertensive patients. After a 2-wk placebo period, 130 patients, aged 35 to 75 y, with diastolic blood pressure (DBP) >or=99 and 110 mm Hg were randomly assigned to olmesartan 20 mg once daily or to valsartan 160 mg once daily according to a prospective, parallel-arm study design. After 4 wk of monotherapy, patients whose BP was not controlled (DBP >or=90 mm Hg) were given combination treatment with HCTZ 12.5 mg for an additional 4 wk. At the end of the placebo period and at the end of each treatment period, clinical and ambulatory BP measurements were recorded. At the end of the combination therapy period, venous blood samples were drawn 2, 4, and 24 h after drug intake for evaluation of HCTZ plasma concentrations. Both combinations induced a greater ambulatory BP reduction than monotherapy. However, mean reduction from baseline in the valsartan/HCTZ-treated patients (-21.5)-14.6 mm Hg for 24 h, -21.8/-14.9 mm Hg for daytime, and -20.4/-13.7 mm Hg for nighttime systolic blood pressure [SBP]/DBP) was greater than in the olmesartan/HCTZ-treated patients )-18.8/-12.3 mm Hg for 24 h, -19.3/-12.8 mm Hg for daytime, and 17.4/-10.6 mm Hg for nighttime SBP/DBP). The difference between the effects of the 2 treatments was significant (P<.01). In particular, compared with monotherapy, the add-on effect of HCTZ 12.5 mg was significantly greater in the valsartan group than in those treated with olmesartan; the difference was more evident for nighttime BP values. Plasma concentrations of HCTZ were significantly greater with valsartan than with olmesartan at each determination time (P<.05). These findings suggest that the addition of HCTZ 12.5 mg to valsartan 160 mg monotherapy produces a greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 mg monotherapy.
Asunto(s)
Antihipertensivos/uso terapéutico , Hidroclorotiazida/uso terapéutico , Hipertensión/tratamiento farmacológico , Imidazoles/uso terapéutico , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Tetrazoles/uso terapéutico , Valina/análogos & derivados , Adulto , Anciano , Antihipertensivos/administración & dosificación , Quimioterapia Combinada , Femenino , Humanos , Hidroclorotiazida/administración & dosificación , Imidazoles/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores de los Simportadores del Cloruro de Sodio/administración & dosificación , Tetrazoles/administración & dosificación , Valina/administración & dosificación , Valina/uso terapéutico , ValsartánRESUMEN
OBJECTIVE: The aim of this study was to compare the chronic effects of four dihydropyridine calcium antagonists with different pharmacologic characteristics, amlodipine, felodipine, lacidipine and manidipine,on blood pressure (BP), heart rate (HR) and plasma norepinephrine (NE) levels in patients with mild to moderate essential hypertension. METHOD: After a 4-week placebo period, 60 patients of both sexes were randomly administered amlodipine 5-10 mg once daily (o.d.) (n = 15); felodipine 5-10 mg o.d. (n = 15); lacidipine 4-6 mg o.d. (n = 15); manidipine 10-20 mg o.d. (n = 15), for 24 weeks, according to a double blind, parallel group design. Initially, for the first 2 weeks, the lowest dose of each drug was used, then higher doses were administered if sitting diastolic blood pressure (DBP) was > 90 mmHg. BP, HR and plasma NE were evaluated at the end of the placebo and active treatment periods. NE was assessed at trough, at peak and after 12 h from drug ingestion. RESULTS: Administration of all four drugs reduced clinic BP to the same level after 24 weeks, whereas HR increased only with felodipine (+ 3.1 bpm; P< 0.05). Significant increases in plasma NE levels were observed after chronic therapy with amlodipine and felodipine (+ 34.9 and + 39.4% respectively; P< 0.01 versus placebo) but not with lacidipine (+ 7.1%, NS) and manidipine (+ 2.9%, NS). CONCLUSIONS: These findings suggest that sympathetic activation occurred during chronic treatment with amlodipine and felodipine, whereas manidipine and lacidipine did not increase plasma noradrenaline at the times measured. The reasons for this difference are unclear; they could be related to the different pharmacological characteristic of the two drugs, lacidipine and manidipine.
Asunto(s)
Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Dihidropiridinas/uso terapéutico , Hipertensión/sangre , Hipertensión/tratamiento farmacológico , Norepinefrina/sangre , Adulto , Anciano , Amlodipino/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Felodipino/uso terapéutico , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Nitrobencenos , Piperazinas , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
The aim of this study was to compare the effect of antihypertensive treatment with valsartan or cavedilol on sexual activity in hypertensive men who were never treated for hypertension. A total of 160 newly diagnosed hypertensive men (diastolic blood pressure [DBP] > or = 95 mm Hg and < 110 mm Hg), aged 40 to 49 years, all married and without any previous sexual disfunction, were enrolled. After a 4-week placebo period, the patients were divided into two groups: a) 120 patients were randomized to receive carvedilol 50 mg once daily or valsartan 80 mg once daily for 16 weeks according to a double-blind, cross-over design; after another 4-week placebo period, patients were crossed over to the alternative regimen for a further 16 weeks; b) 40 patients were treated with placebo according to a single-blind design for 16 weeks. At the screening visit and every 4 weeks thereafter, blood pressure (BP) was evaluated and patients were interviewed by a questionnaire about their sexual activity. Blood pressure was significantly lowered by both treatments, with a 48% of normalization with valsartan and 45% with carvedilol. During the first month of therapy, sexual activity (assessed as number of sexual intercourse episodes per month) declined with both drugs as compared with baseline, although the decrease was statistically significant in the carvedilol (from 8.2 to 4.4 sexual intercourse episodes, P < .01) but not in the valsartan-treated patients (from 8.3 to 6.6 sexual intercourse episodes, not significant). Ongoing with the treatment the sexual activity further worsened with carvedilol (3.7 sexual intercourse episodes per month) while fully recovered and also improved with valsartan (10.2 sexual intercourse episodes per month). The results were confirmed by the cross-over. Erectile dysfunction was a complaint of 15 patients with carvedilol (13.5%), one patient with valsartan (0.9%), and one patient in the placebo group. These findings suggest that carvedilol induces a chronic worsening of sexual activity, whereas valsartan not only does not significantly worsen sexual activity but may even improve it.
Asunto(s)
Antihipertensivos/uso terapéutico , Carbazoles/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Propanolaminas/uso terapéutico , Conducta Sexual/efectos de los fármacos , Tetrazoles/uso terapéutico , Valina/análogos & derivados , Valina/uso terapéutico , Adulto , Antihipertensivos/efectos adversos , Carbazoles/efectos adversos , Carvedilol , Estudios Cruzados , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Propanolaminas/efectos adversos , ValsartánRESUMEN
The aim of this study was to compare the effects of trandolapril and losartan on plasminogen activator inhibitor type 1 (PAI-1) levels and insulin sensitivity in hypertensive postmenopausal women. We studied 89 hypertensive (diastolic blood pressure >90 and <110 mm Hg) postmenopausal women, aged 51 to 60 years not taking any hormone replacement therapy. Diabetic, obese, and smoking patients were excluded. After a 4-week placebo period, they were randomized to receive 2 mg of oral trandolapril (n=45) or 50 mg of oral losartan (n=44) for 12 weeks according to a double-blind, parallel group design. At the end of the placebo and active treatment periods, blood pressure (BP) was measured, plasma samples were drawn to evaluate PAI-1 antigen levels, and insulin sensitivity was assessed. Both trandolapril and losartan reduced systolic BP (by a mean of 16.9 mm Hg and 15.2 mm Hg, respectively, P < .01 v placebo) and diastolic BP (by a mean of 13.1 mm Hg and 11.9 mm Hg, respectively, P < .01 v placebo) with no difference between the two treatments. The PAI-1 antigen levels were significantly decreased by trandolapril (from 36.9+/-21 ng/dL to 27.2+/-17 ng/dL, P < .05), but not by losartan (from 35.3+/-22 ng/dL to 37.1+/-23 ng/dL, P=not significant). Glucose infusion rate was significantly increased by trandolapril (from 6.67+/-0.56 mg/min/kg to 7.9+/-0.65 mg/min/kg, P < .05), but was not significantly modified by losartan (from 6.7+/-0.47 mg/min/kg to 6.9+/-0.50 mg/min/kg, P= not significant). In the trandolapril group the PAI-1 decrease correlated with glucose infusion rate increase (r=0.36, P=.045) These results provide evidence of different effects of angiotensin converting enzyme inhibitors and AT1 antagonists on fibrinolysis and suggest that the PAI-1 decrease induced by angiotensin converting enzyme inhibitors is related to their action on insulin sensitivity and is not dependent on angiotensin II antagonism but rather on other mechanisms. It remains to be seen whether these findings apply to other patient populations than postmenopausal women.
Asunto(s)
Angiotensina II/antagonistas & inhibidores , Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Fibrinólisis/efectos de los fármacos , Hipertensión/sangre , Hipertensión/tratamiento farmacológico , Insulina/sangre , Posmenopausia/sangre , Posmenopausia/efectos de los fármacos , Salud de la Mujer , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Femenino , Humanos , Indoles/uso terapéutico , Resistencia a la Insulina , Lípidos/sangre , Losartán/antagonistas & inhibidores , Losartán/uso terapéutico , Persona de Mediana Edad , Inhibidor 1 de Activador Plasminogénico/sangre , Sensibilidad y EspecificidadRESUMEN
The influence of sleep deprivation during the first part of the night on 24-h ambulatory blood pressure monitoring (ABPM) was studied in 18 normotensive subjects. They underwent two ABPM, one week apart: during the first, they slept from 11 PM to 7 AM, and during the second, from 2 AM to 7 AM. The main differences were observed at dawn, before awakening, when SBP and DBP significantly decreased (P < .01) in the restricted sleep regimen, and during the morning after the recovery sleep, when SBP and HR significantly increased (P < .05). The explanation for these findings is not obvious. We suppose that the decrease in SBP and DBP at dawn might be due to a reorganization of the sleep phases in the restricted sleep regimen, whereas the increase in SBP and HR after awakening might be due to a greater sympathetic activation, as though sleep deprivation was a stressful condition.
Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea/fisiología , Privación de Sueño/fisiología , Adulto , Diástole/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Sístole/fisiologíaRESUMEN
To evaluate the effect of antihypertensive treatment on sexual activity, 90 hypertensive men, aged 40 to 49 years, all married and without history of sexual dysfunction were treated with 100 mg of atenolol or 20 mg of lisinopril for 16 weeks, according to a double-blind, randomized, cross-over design. During the first month of therapy, sexual activity, assessed as number of sexual intercourse episodes per month, significantly declined with both atenolol (from 7.8 +/- 4.3 to 4.5 +/- 2.8, P < .01 v placebo) and lisinopril (from 7.1 +/- 4.0 to 5.0 +/- 2.5, P < .05 v placebo). Ongoing with the treatment, sexual activity tended toward recovery in the lisinopril (7.7 +/- 4.0 sexual intercourse episodes per month, P = NS v placebo), but not in the atenolol group (4.2 +/- 2.8, P < .01 v placebo), with a statistically significant difference between the two drugs (P < .01). The percentage of patients who complained of sexual dysfunction symptoms was significantly higher in the atenolol- than in the lisinopril-treated group (17% v 3%, P < .05). These findings suggest that atenolol induces a chronic worsening of sexual activity, whereas lisinopril causes only a temporary decline.
Asunto(s)
Antihipertensivos/efectos adversos , Atenolol/efectos adversos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Lisinopril/efectos adversos , Caracteres Sexuales , Conducta Sexual/efectos de los fármacos , Adulto , Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Humanos , Libido/efectos de los fármacos , Lisinopril/uso terapéutico , Masculino , Persona de Mediana EdadRESUMEN
The aim of this study was to compare the effect of the beta-adrenergic blocker atenolol and the Angiotensin II type 1 (AT1) receptor antagonist losartan on cognitive function in very elderly hypertensive patients. A total of 120 mild to moderate essential hypertensive (DBP >90 and <105 mmHg) patients, aged 75-89 years, were studied. After a 4-week wash-out period on placebo, they were randomized to receive atenolol 50 mg or losartan 50 mg for 24 weeks according to a parallel arm design. At the end of the placebo period and of each active treatment period, BP was measured (by mercury sphygmomanometer, Korotkoff I and V) and cognitive function was evaluated through three different tests (word list memory, word list recall and word list fluency). Both atenolol and losartan were equally effective in reducing SBP (-22.1 and -23.1 mmHg, respectively, P< 0.01 vs baseline) and DBP (-10.3 and -11.2 mmHg, respectively, P< 0.01 vs baseline). Atenolol treatment did not induce significant changes in any test score, whereas losartan significantly increased the score of both the word list memory (+2.2, P<0.05 vs baseline) and the word list recall test (+2.1, P<0.05 vs baseline). The comparison between losartan and atenolol was significant (P<0.05) for both memory tests. These data suggest that in very elderly hypertensive patients, chronic AT1 receptor blockade by losartan could improve cognitive function, in particular immediate and delayed memory.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Antihipertensivos/farmacología , Atenolol/farmacología , Hipertensión/tratamiento farmacológico , Losartán/farmacología , Memoria/efectos de los fármacos , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Anciano de 80 o más Años , Bloqueadores del Receptor Tipo 1 de Angiotensina II , Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Cognición/efectos de los fármacos , Cognición/fisiología , Método Doble Ciego , Femenino , Humanos , Hipertensión/psicología , Losartán/uso terapéutico , Masculino , Memoria/fisiología , Pruebas PsicológicasRESUMEN
The aim of this double-blind, double-dummy, parallel group study was to compare the effects of delapril-manidipine combination vs a irbesartan-hydrochlorothiazide combination on plasma tissue plasminogen activator (t-PA) and plasmogen activator inhibitor type I (PAI-l) activities in hypertensive patients with type II diabetes mellitus. After a 4-week run-in placebo period, 80 patients (37 male and 43 female), aged 41-65 years, were randomly allocated to an 8-week treatment with delapril 30 mg once daily or irbesartan 150 mg once daily. Thereafter, manidipine l0 mg once daily was added to delapril treatment and hydrochlorothiazide 12.5 mg to irbesartan treatment for a further 8 weeks. Blood pressure (BP), plasma t-PA and PAI-l activities were evaluated at the end of the run-in period, after 4-week monotherapy treatments, and at the end of the combination treatment periods. Both combination treatments, delapril-manidipine and irbesartan-hydrochlorothiazide, produced a greater reduction in systolic BP/diastolic BP (SBP/DBP) values (-27.6/21.8 mmHg and -26.4/20.2 mmHg, respectively) than the respective monotherapies (-15.2/11.7 mmHg with delapril and -16.3/11.3 mmHg with irbesartan). Delapril monotherapy significantly decreased plasma PAI-l activity (-10.4 IU/mI; P<0.05). The addition of manidipine produced a significant increase in t-PA activity (+0.27 IU/mI); P<0.05). Irbesartan monotherapy did not significantly affect the fibrinolytic balance, whereas the addition of hydrochlorothiazide worsened it, producing a significant increase in PAI-l activity (+9.5 IU/ml; P<0.05). In hypertensive patients with type II diabetes mellitus, the combination delapril-manidipine may determine a greater improvement of the fibrinolytic function than the respective monotherapy, while the association irbesartan-hydrochlorothiazide may worsen it.
Asunto(s)
Antihipertensivos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Fibrinólisis/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Compuestos de Bifenilo/uso terapéutico , Dihidropiridinas/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Hidroclorotiazida/uso terapéutico , Hipertensión/complicaciones , Indanos/uso terapéutico , Irbesartán , Masculino , Persona de Mediana Edad , Nitrobencenos , Piperazinas , Inhibidor 1 de Activador Plasminogénico/sangre , Tetrazoles/uso terapéutico , Activador de Tejido Plasminógeno/sangre , Resultado del TratamientoRESUMEN
We investigated in a post hoc analysis the relationship between plasma endothelin (ET-1) levels (immunoreactive ET-1-like material: ir-ET-1) with both casual and noninvasive 24h ambulatory blood pressure monitoring (24h ABPM) values in EH. Fifteen uncomplicated EH patients (casual supine DBP > or = 100 mmHg), 10 males, age 54 +/- 6 years, 13 previously treated, enrolled in an antihypertensive drug trial (casual DBP > or = 100 mmHg), were evaluated. After a four week single-blind placebo wash-out period, measurements of supine casual SBP and DBP (three consecutive readings) and a 24h ABPM (Spacelabs 90207; automatic reading every 15 minutes) were carried out. Plasma ir-ET-1 was measured by radioimmunoassay kit (Amersham, UK). Pearson correlation coefficient tests were used for statistical evaluations. Mean (SD) casual SBP/DBP values were 166(5)/104(2) mmHg. The 24h ABPM mean values were 148(7)/87(3) mmHg. Daytime (07.00-23.00h) and nighttime (23.00-07.00h) SBP/DBP were 153(7)/91(3) and 137(10)/78(5) mmHg, respectively. Plasma ir-ET-1 levels were 0.9(0.5) pmol/l (range 0.3-2.1 pmol/l). Plasma ir-ET-1 was not correlated with casual SBP and DBP, age, serum creatinine and duration of EH. Positive and significant correlations were observed with 24h SBP (r = 0.59), daytime SBP (r = 0.58), nighttime SBP (r = 0.53) and DBP (r = 0.60). Unlike casual BP, ABPM mean values correlate positively with plasma ir-ET-1 in mild to moderate EH.
Asunto(s)
Presión Sanguínea/fisiología , Endotelinas/sangre , Endotelinas/fisiología , Hipertensión/fisiopatología , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The aim of this study was to evaluate the effect of benazepril addition to amlodipine antihypertensive treatment on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. A total of 32 mild to moderate essential hypertensives (DBP>90 and <110 mmHg), aged 30-70 years were studied. After a 4-week placebo period, they were randomized to amlodipine 5 mg o.d. or benazepril 10 mg o.d. or amlodipine 5 mg plus benazepril 10 mg o.d. for 4 weeks, according to a crossover design. At the end of the placebo period and of each active treatment period, blood pressure,AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed using a system, the subcutaneous pretibial interstitial environment with a water manometer. Both amlodipine and benazepril monotherapy significantly reduced SBP (-18.2+/-4 and -17.8+/-4 mmHg, respectively, P<0.01 vs baseline) and DBP (-12.1+/-3 and -11.7+/-3 mmHg, respectively, P<0.01); the reduction was increased by the combination (-24.2+/-5 mmHg for SBP, P<0.001 and -16.8+/-4 mmHg for DBP, P<0.001). Amlodipine monotherapy significantly increased both AFV (+17.1%, P<0.001 vs baseline) and PSTP (+56.6%, P<0.001 vs baseline). As compared to amlodipine alone, the combination produced a less pronounced increase in AFV (+5.5%, P<0.05 vs baseline and P<0.01 vs amlodipine) and PSTP (+20.5%, P<0.05 vs baseline and P<0.01 vs amlodipine). Ankle oedema was clinically evident in 11 patients with amlodipine monotherapy and in three patients with the combination. These results suggest that ACE-inhibitors partially counteract the microcirculatory changes responsible for Ca-antagonists-induced oedema formation.
Asunto(s)
Amlodipino/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Benzazepinas/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Edema/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Tobillo , Estudios Cruzados , Técnicas de Diagnóstico Cardiovascular/instrumentación , Método Doble Ciego , Quimioterapia Combinada , Edema/complicaciones , Edema/diagnóstico , Edema/fisiopatología , Femenino , Humanos , Presión Hidrostática , Hipertensión/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
The purpose of this study was to compare the effects of ramipril and nitrendipine on urinary albumin excretion (UAE) in hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM) and impaired renal function. Forty patients with mild hypertension with NIDDM and persistent albuminuria (> 300 mg/24h) were studied. After a 3-week run-in period on placebo, patients were randomly treated with ramipril 5 mg once daily or nitrendipine 20 mg once daily for 6 months, according to a double-blind design. Blood pressure (BP), UAE, creatinine clearance and glycosilated haemoglobin were evaluated at the end of the placebo period and after 1,3 and 6 months of active treatment. Both ramipril and nitrendipine significantly lowered BP values without affecting glucose homeostasis and renal function. Despite equivalent BP control, only ramipril afforded a significant reduction in UAE, thus suggesting that the antiproteinuric effect of ramipril is at least partially independent of its anti-hypertensive effect.
Asunto(s)
Albuminuria , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Nitrendipino/uso terapéutico , Ramipril/uso terapéutico , Anciano , Albuminuria/etiología , Análisis de Varianza , Intervalos de Confianza , Creatinina/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/orina , Método Doble Ciego , Hemoglobina Glucada/metabolismo , Humanos , Hipertensión/complicaciones , Hipertensión/orina , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Nitrendipino/administración & dosificación , Nitrendipino/efectos adversos , Ramipril/administración & dosificación , Ramipril/efectos adversos , Insuficiencia Renal/etiología , Insuficiencia Renal/fisiopatología , Insuficiencia Renal/orinaRESUMEN
The aim of this study was to compare the effects of ramipril and nitrendipine chronic treatment on urinary albumin excretion (UAE) in hypertensive patients with type II non-insulin-dependent diabetes mellitus (NIDDM) and impaired renal function. A 2-year, prospective, randomised study was conducted on 51 men with a diastolic blood pressure (DBP) > or =95 and < or =105 mm Hg, stable NIDDM, serum creatinine between 1.6 and 3.0 mg/dl and persistent UAE >300 and <2000 mg/24 h. After a 3-month preliminary observation period, during which patients began a low-protein, low-sodium diet, and a subsequent 4-week run-in period on placebo, patients were randomly treated with ramipril 5 mg or nitrendipine 20 mg for 2 years. Both drugs similarly reduced BP without affecting glucose homeostasis. In the ramipril group UAE significantly decreased after only 3 months of treatment, whereas in the nitrendipine group a significant although lesser reduction in UAE was observed only after 1 year. During the second year the UAE% change was not statistically different between the two treatments. Serum creatinine and creatinine clearance showed no significant change with both drugs. The progression of renal insufficiency as assessed by the rate of reduction of creatinine clearance over the 2 years of the study was similar in the ramipril and the nitrendipine groups. In conclusion both ramipril and nitrendipine were associated with a decrease in UAE although such a reduction was earlier and more marked with ramipril. The decline of renal function did not differ significantly between the two treatments.
Asunto(s)
Albuminuria/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Hipertensión/complicaciones , Riñón/fisiopatología , Nitrendipino/uso terapéutico , Ramipril/uso terapéutico , Anciano , Albuminuria/etiología , Creatinina/sangre , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipertensión/orina , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The aim of this double-blind, parallel group study was to compare the effects of nebivolol and atenolol on blood pressure (BP) and insulin sensitivity in hypertensive patients with type II, non-insulin dependent diabetes mellitus (NIDDM). After a 4-week run-in period on placebo, 30 patients (14 males and 16 females) aged 43 to 69 years, with stable NIDDM and mild to moderate hypertension (DBP > or =95 and <116 mm Hg) were randomised to receive either nebivolol 5 mg or atenolol 50 mg, both administered once daily for 6 months. At the end of the placebo and the active treatment periods, supine and standing BP was measured, 24-h urinary C-peptide, HbA1c, plasma glucose and lipid levels were evaluated and an euglycaemic hyperinsulinaemic clamp was performed to evaluate insulin sensitivity: glucose infusion rate during the last 60 min of clamp and total glucose requirements were evaluated. Nebivolol 5 mg once daily was of an equivalent efficacy as atenolol 50 mg once daily at reducing supine and standing systolic and diastolic BP values. Neither beta-blocker adversely affected carbohydrate metabolism in terms of insulin sensitivity, whole body glucose utilization, HbA1c and 24-h urinary C-peptide excretion. No significant changes in cholesterol (total, high density and low density lipoprotein) and triglycerides plasma levels were observed with both beta-blockers. These findings indicate that, in hypertensive patients with NIDDM, ie, in subjects who have established insulin resistance, treatment with nebivolol and atenolol neither further deteriorated insulin sensitivity nor adversely affected the lipid profile.