RESUMEN
BACKGROUND: Essential hypertension has been extensively reported to cause endothelial dysfunction. The aim of this study was to evaluate the effects of barnidipine or lercanidipine, in addition to losartan, on some parameters indicative of endothelial damage and oxidative stress in hypertensive, type 2 diabetic patients. METHODS: One hundred and fifty one patients were randomised to barnidipine, 20 mg/day, or lercanidipine, 20 mg/day, both in addition to losartan, 100 mg/day, for 6 months. We assessed BP every month, in addition, patients underwent ambulatory blood pressure monitoring (ABPM). We also assessed: fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), some markers such as high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α), metalloproteinase-2 (MMP-2) and -9 (MMP-9), soluble vascular adhesion protein-1 (sVCAM-1), soluble intercellular adhesion protein-1 (sICAM-1), isoprostanes and paraoxonase-1 (PON-1). RESULTS: Both barnidipine and lercanidipine resulted in a significant reduction in blood pressure, even if the reduction obtained with barnidipine + losartan was greater than that obtained with lercanidipine + losartan. Data recorded with ABPM also showed a similar trend. Barnidipine + losartan reduced the levels of Hs-CRP, TNF-α, sVCAM-1, sICAM-1, and isoprostanes both compared to baseline and to lercanidipine + losartan. CONCLUSIONS: Barnidipine + losartan gave an improvement of some parameters indicative of endothelial damage and oxidative stress in diabetic and hypertensive patients. TRIAL REGISTRATION: NCT02064218 , ClinicalTrials.gov.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Dihidropiridinas/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Losartán/uso terapéutico , Nifedipino/análogos & derivados , Estrés Oxidativo/efectos de los fármacos , Anciano , Antihipertensivos/efectos adversos , Biomarcadores/sangre , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/efectos adversos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Dihidropiridinas/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Femenino , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Hipertensión/fisiopatología , Italia , Losartán/efectos adversos , Masculino , Persona de Mediana Edad , Nifedipino/efectos adversos , Nifedipino/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
To evaluate the effects of a fixed combination of olmesartan/amlodipine compared with olmesartan or amlodipine alone on some parameters of endothelial damage in diabetic, hypertensive patients.We enrolled 221 patients; 74 were randomized to olmesartan 20âmg, 72 to amlodipine 10âmg, and 75 to olmesartan/amlodipine fixed combination 20/5âmg for 12 months. We assessed blood pressure monthly; in addition, we also assessed at baseline, and after 6 and 12 months, the following parameters: lipoprotein (a), myeloperoxidase (MPO), isoprostanes, and paraoxonase-1 (PON-1). Blood pressure values obtained with fixed olmesartan/amlodipine combination were significantly lower than those reached with single monotherapies. There was a reduction of lipoprotein (a), and isoprostanes levels with olmesartan/amlodipine fixed combination, both compared with baseline, and with single monotherapies. On the other hand, there was an increase of PON-1 with fixed olmesartan/amlodipine combination, both compared with baseline, and with single drugs. All treatments reduced MPO compared with baseline; however, in group-to-group comparison, MPO reduction was greater with olmesartan/amlodipine fixed combination. Fixed combination of olmesartan/amlodipine was more effective than single monotherapies in reducing oxidative stress, especially in increasing PON-1, and reducing isoprostanes levels in diabetic and hypertensive patients.
Asunto(s)
Antihipertensivos/administración & dosificación , Antihipertensivos/farmacología , Diabetes Mellitus Tipo 2/epidemiología , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Estrés Oxidativo/efectos de los fármacos , Adulto , Amlodipino/administración & dosificación , Amlodipino/farmacología , Arildialquilfosfatasa/sangre , Presión Sanguínea , Índice de Masa Corporal , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Imidazoles/administración & dosificación , Imidazoles/farmacología , Isoprostanos/sangre , Masculino , Peroxidasa/sangre , Tetrazoles/administración & dosificación , Tetrazoles/farmacologíaRESUMEN
The aim of this study was to evaluate the effects of lercanidipine or barnidipine on echocardiographic parameters, in hypertensive, type 2 diabetics with left ventricular hypertrophy. One hundred and forty-four patients were randomized to lercanidipine, 20 mg/day, or barnidipine, 20 mg/day, in addition to losartan, 100 mg/day, for 6 months. We evaluated: blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA(1c)), lipid profile, creatinine, estimated glomerular filtration rate (eGFR), sodium, potassium, and acid uric. Echocardiography was performed at baseline and after 6 months. Both lercanidipine and barnidipine decreased blood pressure. Left ventricular mass index was reduced to a greater extent with barnidipine + losartan. Interventricular septal thickness in diastole was reduced by barnidipine + losartan. Posterior wall thickness in diastole was decreased by both treatments, even if barnidipine + losartan were more effective. Ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction was increased by barnidipine + losartan, but not by lercanidipine + losartan. Finally, isovolumetric relaxation and time and left atrial volume index were reduced by barnidipine + losartan, while lercanidipine + losartan did not affect them. In conclusion, barnidipine + losartan provided a greater improvement of echocardiographic parameters compared to lercanidipine + losartan.