An α-glucosidase inhibitor could reduce T-wave alternans in type 2 diabetes patients.

BACKGROUND: We tested the hypothesis that an alpha-glucosidase inhibitor (α-GI), miglitol, is effective in protecting the cardiovascular system in type 2 diabetes mellitus (T2DM). METHODS: We studied 19 hospitalized heart disease patients with T2DM in whom we performed continuous glucose monitoring, Holter electrocardiogram, and ambulatory blood pressure (BP) monitoring simultaneously for 48h. The α-GI miglitol was administered for half of the study period by a cross-over fashion. T-wave alternans (TWA), a marker of future fatal arrhythmic events, was also analyzed by Holter ECG. RESULTS: Of the 19 patients, the measures of glucose variability were significantly lower during miglitol therapy than in control period. BP variability was similar with/without miglitol. However, TWA was significantly lower during the miglitol period compared to control period (63±4.8 vs. 75.8±5.1µV, p=0.032). CONCLUSION: An α-GI, miglitol, can reduce TWA by reducing the fluctuation of glucose in heart disease patients with T2DM.

Comparison of morning vs bedtime administration of the combination of valsartan/amlodipine on nocturnal brachial and central blood pressure in patients with hypertension.

The aim of this study was to compare the effect of morning and bedtime administration of valsartan/amlodipine combination therapy (80/5 mg) on nocturnal brachial and central blood pressure (BP) measured by ambulatory BP monitoring in patients with hypertension. This was a 16-week prospective, multicenter, randomized, open-label, crossover, noninferiority clinical trial. Patients underwent 24-hour ambulatory BP monitoring at randomization, at switching, and at the end of the study. Twenty-three patients (mean age, 68.0 years) were studied. The difference in nocturnal brachial systolic BP between the morning and bedtime administrations of combination valsartan/amlodipine was -3.2 mm Hg, and the two-sided 95% confidence interval ranged from -6.8 to 0.4 mm Hg. The difference in nocturnal central systolic BP was -4.0 mm Hg (95% confidence interval, -7.6 to -0.4 mm Hg). The upper limit of the 95% confidence interval was below the margin of 3.0 mm Hg in both nocturnal brachial and central systolic BP, confirming the noninferiority of morning administration to the bedtime administration of valsartan/amlodipine combination therapy.

Comparison of ambulatory blood pressure-lowering effects of higher doses of different calcium antagonists in uncontrolled hypertension: the Calcium Antagonist Controlled-Release High-Dose Therapy in Uncontrolled Refractory Hypertensive Patients (CARILLON) Study.

BACKGROUND: Data are sparse regarding ambulatory blood pressure (BP) reduction of up-titration from a standard dose to a high dose in both nifedipine controlled-release (CR) and amlodipine. This was a prospective, randomized, multicenter, open-label trial. PATIENTS AND METHODS: Fifty-one uncontrolled hypertensives medicated by two or more antihypertensive drugs including a renin-angiotensin system inhibitor and a calcium antagonist were randomly assigned to either the nifedipine CR (80 mg)/candesartan (8 mg) group or the amlodipine (10 mg)/candesartan (8 mg) group. RESULTS: The changes in 24-hr BP were comparable between the groups. The nifedipine group demonstrated a significant decrease in their urinary albumin creatinine ratio, whereas the amlodipine group demonstrated a significant decrease in their NTproBNP level. However, there was no significant difference in any biomarkers between the two groups. CONCLUSION: Nifedipine showed an almost equal effect on ambulatory blood pressure as amlodipine. Their potentially differential effects on renal protection and NTproBNP should be tested in larger samples.

Differing Effects of Aliskiren/Amlodipine Combination and High-Dose Amlodipine Monotherapy on Ambulatory Blood Pressure and Target Organ Protection.

The aim of this study was to compare an aliskiren/amlodipine combination with high-dose amlodipine monotherapy on ambulatory blood pressure monitoring (ABPM) and organ protection. The study was a prospective, randomized, multicenter, open-label trial in elderly essential hypertensive patients. A total of 105 patients with clinic BP (CBP) ≥140/90 mm Hg with amlodipine 5 mg were randomly allocated to aliskiren (150-300 mg)/amlodipine (5 mg) (ALI/AML group, n=53) or high-dose amlodipine (10 mg) (h-dAML group, n=52) and treated for 16 weeks. Each patient's CBP, ABPM, urine albumin-to-creatinine ratio (UACR), and brachial-ankle pulse wave velocity (baPWV) were measured at baseline and at the end of the study. The ALI/AML and h-dAML groups showed similarly reduced mean 24-hour SBP, daytime SBP, nighttime SBP, and baPWV. However, UACR reduction was significantly greater in the ALI/AML group (P=.02). ALI/AML was significantly less effective in reducing early-morning BP (P=.002) and morning BP surge (P=.001) compared with h-dAML.

Differential effects of aliskiren/amlodipine combination and high-dose amlodipine monotherapy on endothelial function in elderly hypertensive patients.

BACKGROUND: The aim of this study was to compare the effects of direct renin inhibitor, aliskiren, and amlodipine combination therapy with those of high-dose amlodipine monotherapy on endothelial function in elderly hypertensive patients. METHODS: Participants included 105 patients (mean age 77 years) who had receive 5mg amlodipine for 4 weeks. Patients were allocated to the aliskiren/amlodipine group (AL/AM) or the high-dose amlodipine (AM) group. The AL/AM group received 150mg aliskiren in addition to 5mg amlodipine for 8 weeks; then the dose of aliskiren was doubled to 300mg for another 8 weeks. The AM group received 10mg amlodipine for 16 weeks. Of the 105 patients, 87 who underwent measurements of brachial flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) before and after the study were included in the analysis. RESULTS: Blood pressure-lowering effects were similar in the 2 groups. Plasma renin activity significantly decreased in the AL/AM group (P < 0.001) but increased in the AM group (P < 0.001). Improvement of FMD was found in the AL/AM group (2.6% to 3.7%, P = 0.001) but not in the AM group, while NMD did not change in either group. The changes in 24-hour systolic blood pressure (r = -0.60, P < 0.001) and diastolic blood pressure (r = -0.46, P = 0.004) were significantly correlated with improvement of FMD in the AL/AM group but not in the AM group. CONCLUSION: Addition of aliskiren improved endothelial function in elderly hypertensive patients treated with amlodipine. CLINICAL TRIAL REGISTRY NUMBER: UMIN000010163.

Differential effects of strict blood pressure lowering by losartan/hydrochlorothiazide combination therapy and high-dose amlodipine monotherapy on microalbuminuria: the ALPHABET study.

We investigated the effects of losartan/hydrochlorothiazide (HCTZ) fixed combination therapy and high-dose amlodipine monotherapy on BP measurements and target organ protection. In this open-label multicenter trial, hypertensive patients were randomly allocated to receive losartan 50 mg or amlodipine 5 mg for 4 weeks, and the treatments were changed to combination of losartan 50 mg/HCTZ 12.5 mg or amlodipine 10 mg for a further 4 weeks. A total of 91 hypertensive patients (age 63.6 years), 47 in the losartan/HCTZ group and 44 in amlodipine group, were enrolled. After 8 weeks, the clinic BP, home BP, and 24-hour ambulatory BP were successfully controlled to the same level in both treatment groups (P < .001). Furthermore, both groups showed the same degree of BP reduction in the 24-hour, daytime, and nighttime (P < .001). B-type natriuretic peptide (BNP) also significantly decreased to the same level in both groups, whereas the reduction of urinary albumin/creatinine ratio (UACR) was greater in the losartan/HCTZ group than in the high-dose amlodipine group (-47.6% vs 2.4%, P < .001). Losartan/HCTZ combination and high-dose amlodipine have similar effects on clinic, home, and ambulatory BP control and BNP reduction, whereas losartan/HCTZ has superior effect on UACR reduction when compared with high-dose amlodipine.

Regional differences in hypertensive cardiovascular remodeling between fishing and farming communities in Japan.

BACKGROUND: Effects of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) intake on the cardiovascular system have been reported, and thus we hypothesized that the prevalence of hypertensive cardiovascular remodeling would be lower in a fishing than a farming community. METHODS: We recruited 263 essential hypertensives from a fishing and 333 from a farming village; all subjects were ≥40 years (mean 73 years; 42% men). They were cross-sectionally examined for serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), asymmetric dimethylarginine (ADMA) levels, left ventricular mass index (LVMI), and common-carotid artery (CCA) and internal-carotid artery (ICA) intima-media thickness (IMT). RESULTS: Compared to the patients in the farming village, those in the fishing village had higher serum EPA and DHA levels (63.3 vs.70.9 µg/ml, 137.2 vs.157.8 µg/ml) and lower ADMA levels (0.49 vs.0.47 nmol/ml; all P < 0.05). LVMI and both CCA-IMT and ICA-IMT levels were lower in the fishing than the farming village (113.2 vs.121.6 g/m(2), 0.88 vs.0.94 mm, 1.10 vs.1.17 mm: all P < 0.01) even after adjustment for age, sex, body mass index (BMI), duration of hypertensive medication, number of antihypertensive medications, and 24-h systolic blood pressure (SBP) level. The differences in LVMI and IMT levels between these communities also remained unchanged (all P < 0.01) after additional adjustment for the regional differences in EPA, DHA, and ADMA levels. A multivariable linear regression analysis showed that the difference in place of residence was independently associated with LVMI as well as with both CCA-IMT and ICA-IMT levels (all P < 0.01). CONCLUSION: The prevalence of cardiovascular remodeling was significantly lower in patients in the fishing community than in those in the farming community. Further investigations are required to explain the mechanisms underlying this association.

Comparison of valsartan and amlodipine on ambulatory and morning blood pressure in hypertensive patients.

BACKGROUND: Cardiovascular events occur most frequently in the morning. We aimed to study the effects of monotherapy with the long-acting angiotensin II receptor blocker valsartan compared with the long-acting calcium antagonist amlodipine on ambulatory and morning blood pressure (BP). METHODS: We performed ambulatory BP monitoring before and after once-daily dose of valsartan (valsartan group, n = 38) and amlodipine (amlodipine group, n = 38) therapy in 76 hypertensive patients. To achieve the target BP of < or =140/90 mm Hg, valsartan was titrated from 40 mg/day to 160 mg/day (mean dose 124 mg/day) and amlodipine was titrated from 2.5 mg/day to 10 mg/day (mean dose 6.4 mg/day). RESULTS: Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (P <.002). However, the antihypertensive effect of amlodipine was superior to that of valsartan in clinical SBP (-26 mm Hg v -13 mm Hg, P =.001) and 24-h SBP (-14 mm Hg v -7 mm Hg, P =.008). In addition, morning SBP was significantly reduced by amlodipine from 156 to 142 mm Hg (P <.001) but not by valsartan. Both agents reduced lowest night SBP to a similar extent (amlodipine 121 to 112 mm Hg, P <.001; valsartan 123 to 114 mm Hg, P <.002). Reduction in morning SBP surge (morning SBP minus lowest night SBP) was significantly greater in patients treated with amlodipine compared with those treated with valsartan (-6.1 mm Hg v +4.5 mm Hg, P <.02). CONCLUSIONS: Amlodipine monotherapy was more effective than valsartan monotherapy in controlling 24-h ambulatory BP and morning BP in hypertensive patients.