Hypertension research : official journal of the Japanese Society of Hypertension
-
In the presence of salt, aldosterone causes hypertension and organ damage via the mineralocorticoid receptor (MR) through various mechanisms. MR antagonists are considered to be potassium-sparing diuretics that exert their effect by blocking MR in the kidney, and they are not the first choice for treating hypertension. However, the importance and usefulness of inhibiting aldosterone in the management of hypertension have recently been revealed in both the basic and clinical fields. ⋯ This differentiation is divided into two types due to the differences in their features and differences in their contraindications in Japan. Based on a number of studies on MR antagonists that have been recently published, the diseases and clinical conditions targeted by MR antagonists appear to be likely to increase in the future. In Japan, we consider it necessary to carefully differentiate spironolactone from eplerenone in regard to their intended uses.
-
Randomized Controlled Trial Multicenter Study
Cardiovascular outcomes in the first trial of antihypertensive therapy guided by self-measured home blood pressure.
Hypertension guidelines recommend blood pressure self-measurement at home (HBP), but no previous trial has assessed cardiovascular outcomes in hypertensive patients treated according to HBP. The multicenter Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP; 2001-2010) trial involved 3518 patients (50% women; mean age 59.6 years) with an untreated systolic/diastolic HBP of 135-179/85-119 mm Hg. In a 2 × 3 design, patients were randomized to usual control (125-134/80-84 mm Hg (UC)) vs. tight control (<125/<80 mm Hg (TC)) of HBP and to initiation of drug treatment with angiotensin converting enzyme inhibitors, angiotensin receptor blockers or calcium channel blockers. ⋯ In all patients combined, the risk of the primary end point independently increased by 41% (6-89%; P=0.019) and 47% (15-87%; P=0.0020) for a 1-s.d. increase in baseline (12.5 mm Hg) and follow-up (13.2 mm Hg) systolic HBP. The 5-year risk was minimal (≤1%) if on-treatment systolic HBP was 131.6 mm Hg or less. HOMED-BP proved the feasibility of adjusting antihypertensive drug treatment based on HBP and suggests that a systolic HBP level of 130 mm Hg should be an achievable and safe target.
-
Randomized Controlled Trial Multicenter Study
Comparison of medium-dose losartan/hydrochlorothiazide and maximal-dose angiotensin II receptor blockers in the treatment of Japanese patients with uncontrolled hypertension: the Kobe-CONNECT Study.
The objective of this study is to examine the effects of thiazide diuretics, plus medium-dose losartan versus maximal-dose angiotensin II receptor blockers (ARBs) on blood pressure (BP) in Japanese patients with uncontrolled hypertension despite the use of medium-dose ARBs. Hypertensive patients in whom BP was inadequately controlled by treatment with medium-dose ARBs alone or with calcium-channel blockers were enrolled. Patients were randomly assigned to a fixed-dose combination of 50 mg per day losartan and 12.5 mg per day hydrochlorothiazide (HCTZ; n=98), or to a maximal dose of current ARBs (n=95). ⋯ The concomitant usage of losartan and HCTZ had no influence on glucose metabolism and lipid profiles. Declines in plasma N-terminal pro-brain natriuretic peptide levels and urinary albumin excretion were observed in the losartan/HCTZ group, but not in the maximal-dose ARB group. Switching from medium-dose ARBs to losartan plus HCTZ reduced both office and home BP efficiently in patients with uncontrolled hypertension.
-
The aim of this study was to investigate whether toe-brachial index (TBI) is more strongly associated with albuminuria or estimated glomerular filtration rate (eGFR) than ankle-brachial index (ABI), and thus is a more suitable tool for evaluating the association between peripheral artery disease (PAD) and diabetic nephropathy than ABI in patients with type 2 diabetes. We evaluated the relationships between ABI or TBI and the degree of urinary albumin excretion or eGFR, as well as the major cardiovascular risk factors, in 390 patients with type 2 diabetes. Furthermore, we compared the area under the receiver-operator characteristic curve (AUC) of TBI or ABI for albuminuria or chronic kidney disease (CKD). ⋯ The AUCs of TBI for albuminuria (P=0.0002) and CKD (P=0.0322) were significantly greater than those of ABI. In conclusion, TBI is associated more strongly with albuminuria and eGFR than ABI in patients with type 2 diabetes. Our study suggests that TBI may be a more suitable tool for evaluating the association between PAD and diabetic nephropathy than ABI in patients with type 2 diabetes.
-
In male coupling factor 6 (CF6)-overexpressing transgenic (TG) mice, a high-salt diet induces hypertension and cardiac systolic dysfunction with excessive reactive oxygen species generation. However, the role of gender in CF6-mediated pathophysiology is unknown. We investigated the effects of ovariectomy and estrogen replacement on hypertension, cardiac dysfunction and Rac1 activity, which activates radical generation and the mineralocorticoid receptor, in female TG mice. ⋯ The ratios of Rac1 bound to guanosine triphosphate (Rac1-GTP) to total Rac1 in the heart and kidneys were increased in the ovariectomized TG mice, and estrogen replacement abolished the CF6-mediated pathophysiology induced under the high-salt diet conditions. The overexpression of CF6 induced salt-sensitive hypertension, complicated by systolic cardiac dysfunction, but its onset was delayed in females. Estrogen has an important role in the regulation of CF6-mediated pathophysiology, presumably via the downregulation of Rac1.