RESUMO
Vascular damage is aggravated in animal models of hypertension with mineralocorticoid (MR) excess and in hypertensive patients with primary hyperaldosteronism. MR antagonism has shown to provide effective blood pressure (BP)-control in patients with treatment resistant hypertension (TRH), but the concurrent effects on the vasculature have not been examined. In a randomized, double-blinded, placebo-controlled parallel-group study, 51 patients with TRH received either eplerenone 50 mg or placebo for 6 months together with additional antihypertensives titrated to achieve a BP target of <140/90 mm Hg. Pulse wave velocity (PWV), augmentation index (AIx), augmentation pressure (AP), AP normalized to a heart rate of 75/min (AP@HR75), renal resistive index (RRI), intima-media thickness (IMT) and urinary albumin excretion rate (UAER) were assessed before and after treatment. PWV was reduced only with eplerenone (from 11.3±3.6 to 9.8±2.6 m/s, PË.001), but not with placebo (10.3±2.0 to 10.1±1.8 m/s, P=.60), despite similar reductions in BP (-35±20/-15±11 mm Hg vs -30±19/-13±7 mm Hg, n.s.). Further, reductions in AP and AP@HR75 were greater with eplerenone, while changes in AIx, RRI, IMT and UAER were similar. Our data show that eplerenone beneficially affects markers of arterial stiffness and wave reflection in patients with TRH, independently of BP lowering. These data add to the evidence that MR antagonism should be the preferred treatment option in TRH.
Assuntos
Vasoespasmo Coronário/tratamento farmacológico , Hipertensão/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Espironolactona/análogos & derivados , Rigidez Vascular/efeitos dos fármacos , Idoso , Determinação da Pressão Arterial/instrumentação , Espessura Intima-Media Carotídea/instrumentação , Vasoespasmo Coronário/fisiopatologia , Método Duplo-Cego , Eplerenona , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Estudos Prospectivos , Análise de Onda de Pulso/instrumentação , Albumina Sérica Humana/urina , Espironolactona/administração & dosagem , Espironolactona/farmacologiaRESUMO
BACKGROUND: Hyperaldosteronism is well known cause of secondary hypertension. However, the importance of aldosterone for the much larger group of patients with primary hypertension is less clear. We hypothesized that in young subjects with primary hypertension, the rise of plasma aldosterone levels in response to head-up tilt testing as a stress stimulus is exaggerated. METHODS: Hemodynamics (blood pressure (BP), heart rate (HR), cardiac index (CI), and total peripheral vascular resistance index (TPRI), all by TaskForce monitor) and hormones (plasma renin activity (PRA), angiotensin II (Ang II), aldosterone) were measured before and during 30 minutes of head-up tilt in 45 young hypertensive and 45 normotensive subjects. RESULTS: BP, HR, CI, and TPRI all increased in response to head-up tilt, with no difference between groups. There was no difference in baseline PRA, Ang II, and aldosterone between groups. During head-up tilt, PRA, and Ang II levels increased similarly. However, aldosterone levels increased to a greater extent in the hypertensive vs. normotensive subjects (P = 0.0021). CONCLUSIONS: Our data suggest that an increased release of aldosterone in response to orthostatic stress is a feature of early primary hypertension. The similar increase in PRA and Ang II suggests a potential role for secretagogues of aldosterone other than Ang II in this response. In addition to its established role in secondary hypertension, dysregulation of aldosterone release might contribute to the development of primary arterial hypertension.
Assuntos
Aldosterona/sangue , Biomarcadores/sangue , Pressão Sanguínea , Hipertensão/diagnóstico , Postura , Sistema Renina-Angiotensina , Teste da Mesa Inclinada/métodos , Adulto , Fatores Etários , Angiotensina II/sangue , Estudos de Casos e Controles , Frequência Cardíaca , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Valor Preditivo dos Testes , Renina/sangue , Fatores de Tempo , Regulação para Cima , Resistência Vascular , Adulto JovemRESUMO
BACKGROUND: Mineralocorticoid receptor antagonists are increasingly used in patients with treatment-resistant hypertension (TRH). There is experimental evidence for blood pressure (BP) independent effects of mineralocorticoid receptor blockade on cardiovascular target organ damage. We hypothesized that low-dose eplerenone (50âmg) will reduce left ventricular mass (LVM) beyond its BP-lowering effects. METHODS: We performed a randomized, double-blind, placebo-controlled, parallel group study in 51 patients with TRH. Patients were allocated to receive either eplerenone 50âmg or placebo for 6 months, while other antihypertensive agents could be added in both groups to achieve a BP target of less than 140/90âmmHg. LVM was assessed by MRI before and after treatment. RESULTS: Baseline office BP was similar in the eplerenone and the placebo group (166â±â21/91â±â15 versus 159â±â19/94â±â8âmmHg, n.s.). BP was similarly reduced in the eplerenone versus the placebo group (-35â±â20/-15â±â11 versus -30â±â19/-13â±â7âmmHg, n.s.). However, LVM was reduced only in the eplerenone group (from 155â±â33 to 136â±â33âg, Pâ<â0.001), but not in the placebo group (152â±â32 versus 148â±â38âg, Pâ=â0.45). CONCLUSIONS: Despite similar BP-lowering, only patients with TRH who were allocated to eplerenone experienced a reduction of LVM. Thus, our data suggest that in patients with TRH, mineralocorticoid receptor antagonists should be used preferentially in order to achieve an effective reduction of LVM along with the improvement of BP control.