Hypertension research : official journal of the Japanese Society of Hypertension
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Randomized Controlled Trial Multicenter Study
Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker.
Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) with the combination of an angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) is generally well-established as a treatment for nephropathy, this treatment is not fully effective in some patients. Based on the recent evidence implicating aldosterone in renal disease progression, this study was conducted to examine the efficacy of blockade with three different mechanisms by adding an aldosterone blocker in patients who do not respond adequately to the dual blockade. A 1-year randomized, open-label, multicenter, prospective controlled study was conducted, in which 32 non-diabetic nephropathy patients with proteinuria exceeding 0.5 g/day were enrolled after more than 12 weeks of ACE-I (5 mg enalapril) and ARB (50 mg losartan) combination treatment. ⋯ The decreases in urinary protein and urinary type IV collagen were not accompanied by a decrease in blood pressure. Mean serum creatinine, potassium and blood pressure did not change significantly by either treatment. In conclusion, triple blockade of the RAAS was effective for the treatment of proteinuria in patients with non-diabetic nephropathy whose increased urinary protein had not responded sufficiently to a dual blockade.
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Randomized Controlled Trial
Continuous positive airway pressure improves daytime baroreflex sensitivity and nitric oxide production in patients with moderate to severe obstructive sleep apnea syndrome.
Individuals with obstructive sleep apnea syndrome (OSAS) are at high risk for cardiovascular morbidity and mortality. The effects of OSAS severity and nocturnal continuous positive airway pressure (CPAP) on daytime baroreflex sensitivity (BRS) and nitric oxide (NO) production were investigated in OSAS patients. Fifty-one consecutive males with OSAS and 29 age-matched healthy men underwent the Valsalva test and standard polysomnography. ⋯ The BRS index for phase IV and the Valsalva ratio were significantly increased in the CPAP group after the 3-month treatment period but remained unchanged in the non-CPAP group of OSAS patients. The daytime BRS index and NO production were thus inversely related to the severity of OSAS, and successful CPAP treatment improved these parameters in patients with moderate to severe OSAS. CPAP may therefore reduce the risk of cardiovascular complications due to endothelial dysfunction or increased sympathetic activity.
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Randomized Controlled Trial
Angiotensin I-converting enzyme inhibitor improves reactive hyperemia in elderly hypertensives with arteriosclerosis obliterans.
Endothelial function in elderly hypertensive patients with arteriosclerosis obliterans has not been evaluated. We examined whether antihypertensive drugs improve vasodilatory response to reactive hyperemia of the limbs in elderly hypertensive patients (83 +/- 8 [SD] years) without (n=46, 0.9 < or = ankle-brachial pressure index < or = 1.4) and with (n=24) arteriosclerosis obliterans (ankle-brachial pressure index < 0.2). Patients were randomized for treatment with monotherapy of either temocapril (14 with and 26 without arteriosclerosis obliterans) or amlodipine (10 with and 20 without arteriosclerosis obliterans) for 6 months. ⋯ Response to nitroglycerin (0.3 mg) was not changed by either drug. Treatment with temocapril significantly improved maximum reactive hyperemic flow of not only the legs and forearms in control hypertensives but also the legs and forearms in patients with arteriosclerosis obliterans, and attenuated the worsening of activity of daily living in these patients, although treatment with amlodipine did not. These results suggest that the angiotensin-converting enzyme inhibitor temocapril has a beneficial effect on endothelial function in elderly patients with arteriosclerosis obliterans.
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Randomized Controlled Trial Clinical Trial
Antiproteinuric effects of combined antihypertensive therapies in patients with overt type 2 diabetic nephropathy.
Combined antihypertensive therapy plays a crucial role in achieving targeted blood pressure reductions and renoprotection. We therefore compared the antihypertensive and antiproteinuric effects of combined therapy with either a calcium channel blocker (CCB) plus an angiotensin II receptor blocker (ARB) or an angiotensin converting enzyme inhibitor (ACE-I) plus an ARB in patients with type 2 diabetes mellitus complicated by overt nephropathy and mild to moderate hypertension. After a 12-week dietary control period, diabetic patients with mildly to moderately impaired renal function were randomly assigned to either a CCB (amlodipine 5 mg once daily) or an ACE-I (temocapril 2 mg once daily) for 12 weeks (monotherapy period). ⋯ Although the latter combination had a more profound effect, it was associated with an increased serum potassium concentration and worsening of renal anemia. Thus, the combination of a CCB and an ARB should be the first line antihypertensive therapy in those with overt diabetic nephropathy. The long-term efficacy of these combined antihypertensive therapies will need to be further addressed in a future study.