Losartan/hydrochlorothiazide combination is safe and effective for morning hypertension in Very-Elderly patients.

Morning hypertension is an independent risk for cerebrovascular and cardiovascular events. Although the prevalence of morning hypertension increases with age, treatment of morning hypertension has not been established, particularly in Very-Elderly patients. We compared the safety and efficacy of a losartan/hydrochlorothiazide (HCTZ) combination in controlling morning hypertension between Very-Elderly (≥75 years) and Young/Elderly patients (<75 years). This study was a subanalysis of the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy study, in which patients with morning hypertension (≥135/85 mmHg) received a 50-mg losartan/12.5-mg HCTZ combination tablet (combination therapy) or 100-mg losartan (high-dose therapy) for 3 months. High adherence rates and few adverse effects were observed in Very-Elderly patients receiving combination (n = 32) and high-dose (n = 34) therapies and in Young/Elderly patients receiving combination (n = 69) and high-dose (n = 66) therapies. Baseline morning systolic BP (SBP) was similar in both age groups receiving either therapy. Morning SBP was reduced by 20.2 and 18.1 mmHg with combination therapy and by 7.1 and 9.1 mmHg with high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Morning BP target (<135/85 mmHg) was achieved in 40.6% and 55.1% by combination therapy and in 14.7% and 24.2% by high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Neither therapy changed renal function and serum potassium in Very-Elderly patients. In conclusion, the losartan/HCTZ combination was safe and effective in controlling morning hypertension in Very-Elderly as well as Young/Elderly patients. In addition, combination therapy was also superior to high-dose therapy for lowering morning SBP in Very-Elderly patients.

Nifedipine controlled-release 40 mg b.i.d. in Japanese patients with essential hypertension who responded insufficiently to nifedipine controlled-release 40 mg q.d.: a phase III, randomized, double-blind and parallel-group study.

This phase III, multicenter, randomized, double-blind, parallel-group study compared the efficacy and safety of nifedipine controlled-release (CR) 40 mg twice daily (b.i.d.) and once daily (q.d.) in 325 Japanese patients with essential hypertension uncontrolled with nifedipine CR 40 mg q.d. (ClinicalTrials.gov record: NCT01287260). The primary endpoint was the change from baseline in trough seated diastolic blood pressure (DBP) after 8 weeks. Nifedipine CR 40 mg b.i.d. showed significantly greater reductions in trough seated DBP (-7.7±0.6 mm Hg vs. -3.6±0.6 mm Hg) and trough seated systolic blood pressure (BP) (-11.1±0.9 mm Hg vs. -3.7±0.9 mm Hg) after 8 weeks of treatment compared with nifedipine CR 40 mg q.d. (both P<0.0001). At week 8, BP target achievement and responder rates were higher with nifedipine CR 40 mg b.i.d. (21.5% and 42.4% vs. 10.3% and 19.5%, respectively). Adverse events considered related to the study drug were reported in 9.0 and 9.7% of patients receiving nifedipine CR 40 mg b.i.d. and q.d., respectively. The frequency of drug-related adverse events commonly reported with nifedipine CR (headache, hot flush, palpitations, peripheral edema, hypotension, dizziness, tachycardia) was low and the results were similar between the treatment groups. In conclusion, a higher dose of nifedipine CR was associated with greater efficacy and a safety profile similar to that of the currently approved dose (40 mg q.d.) in Japanese patients with essential hypertension, and it may offer a valuable treatment choice for patients who do not achieve target BP levels with standard treatment.

Reduction in morning blood pressure is a key factor for ameliorating urinary albumin excretion in patients with morning hypertension irrespective of treatment regimen.

BACKGROUND: The Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study has shown that losartan/hydrochlorothiazide (HCTZ) combination is superior to high-dose losartan in not only reducing morning systolic blood pressure (SBP) but also ameliorating urinary albumin excretion (UAE) after 3-month treatment. The purpose of the present study was to investigate factors associated with UAE reduction in on-treatment patients with morning hypertension. METHODS AND RESULTS: A total of 95 patients registered in the MAPPY study were analyzed. Patients were treated with either a losartan/HCTZ combination regimen (n=47) or a high-dose losartan regimen (n=48). Three-month treatment significantly reduced morning SBP, evening SBP, and clinic SBP (P<0.001, P<0.05, and P<0.01, respectively). UAE and serum uric acid were significantly decreased (P<0.01 for both) without the change in estimated glomerular filtration rate. Multiple linear regression analysis indicated that %morning SBP reduction and baseline UAE were independent determinants of the UAE reduction (P=0.001 for both). After adjustments for the reduction in morning-evening SBP difference, baseline UAE, and %uric acid reduction, estimated %UAE reduction level was positively correlated with the tertiles of the increasing %morning SBP reduction level (P=0.031 for trend). Moreover, subgroup analysis showed that morning SBP reduction was an independent determinant of UAE reduction in both treatment regimens. CONCLUSIONS: Reduction in morning SBP was a key factor in UAE reduction in patients with morning hypertension, irrespective of treatment regimen.

Losartan/hydrochlorothiazide combination vs. high-dose losartan in patients with morning hypertension--a prospective, randomized, open-labeled, parallel-group, multicenter trial.

The treatment of morning hypertension has not been established. We compared the efficacy and safety of a losartan/hydrochlorothiazide (HCTZ) combination and high-dose losartan in patients with morning hypertension. A prospective, randomized, open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients with morning hypertension evaluated by home blood pressure (BP) self-measurement. Patients were randomly assigned to receive a combination therapy of 50 mg losartan and 12.5 mg HCTZ (n=109) or a high-dose therapy with 100 mg losartan (n=107), each of which were administered once every morning. Primary efficacy end points were morning systolic BP (SBP) level and target BP achievement rate after 3 months of treatment. At baseline, BP levels were similar between the two therapy groups. Morning SBP was reduced from 150.3±10.1 to 131.5±11.5 mm Hg by combination therapy (P<0.001) and from 151.0±9.3 to 142.5±13.6 mm Hg by high-dose therapy (P<0.001). The morning SBP reduction was greater in the combination therapy group than in the high-dose therapy group (P<0.001). Combination therapy decreased evening SBP from 141.6±13.3 to 125.3±13.1 mm Hg (P<0.001), and high-dose therapy decreased evening SBP from 138.9±9.9 to 131.4±13.2 mm Hg (P<0.01). Although both therapies improved target BP achievement rates in the morning and evening (P<0.001 for both), combination therapy increased the achievement rates more than high-dose therapy (P<0.001 and P<0.05, respectively). In clinic measurements, combination therapy was superior to high-dose therapy in reducing SBP and improving the achievement rate (P<0.001 and P<0.01, respectively). Combination therapy decreased urine albumin excretion (P<0.05) whereas high-dose therapy reduced serum uric acid. Both therapies indicated strong adherence and few adverse effects (P<0.001). In conclusion, losartan/HCTZ combination therapy was more effective for controlling morning hypertension and reducing urine albumin than high-dose losartan.

Habitual coffee but not green tea consumption is inversely associated with metabolic syndrome: an epidemiological study in a general Japanese population.

In Japan, metabolic syndrome used to be rare, and the level of coffee consumption was low. However, the Japanese life style has been changing rapidly, and these changes have been associated with a steady increase in the frequency of metabolic syndrome and with greater consumption of coffee. We examined the relationship between metabolic syndrome and the consumption of coffee or green tea. A total of 1902 Japanese aged over 40 years (785 men and 1117 women) received population-based health check-up in 1999. We measured components of metabolic syndrome (blood pressure, waist circumference, fasting plasma glucose, and lipid profiles). Eating and drinking patterns were evaluated by a food frequency questionnaire. Multivariate analyses were performed to clarify the association between coffee or green tea consumption and the components of metabolic syndrome. All components of metabolic syndrome except for HDL-cholesterol were significantly (p<0.01) and inversely related to coffee but not green tea consumption by multivariate analysis after adjusting for confounding factors. The larger was the number of components of metabolic syndrome, the lower was the level of coffee consumption (p<0.0001). In addition, there was a high frequency of metabolic syndrome in small coffee drinkers. Thus, coffee but not green tea consumption was inversely associated with metabolic syndrome.

Safety and efficacy of repeated sauna bathing in patients with chronic systolic heart failure: a preliminary report.

BACKGROUND: We sought to determine the safety and efficacy of repeated 60 degrees C sauna bathing in patients with chronic systolic congestive heart failure (CHF). METHODS AND RESULTS: This study included 15 hospitalized CHF patients (New York Heart Association class = 2.8 +/- 0.4) in stable clinical condition on conventional treatments. Sauna bathing was performed once per day for 4 weeks. Repeated sauna bathing was safely completed without any adverse effects in all patients. Symptoms improved in 13 of 15 patients after 4 weeks. Sauna bathing decreased systolic blood pressure without affecting heart rate, resulting in significant decrease in the rate-pressure product (6811 +/- 1323 to 6292 +/- 1093). Echocardiographic left ventricular ejection fraction was significantly increased from 30 +/- 11 to 34 +/- 11%. Sauna bathing significantly improved exercise tolerance manifested by prolonged 6-minute walking distance (388 +/- 110 to 448 +/- 118 m), increased peak respiratory oxygen uptake (13.3 +/- 1.8 to 16.3 +/- 2.1 mL/kg/min), and enhanced anaerobic threshold (9.4 +/- 1.2 to 11.5 +/- 1.9 mL/kg/min). Four-week bathing significantly reduced plasma epinephrine (40 +/- 42 to 21 +/- 23 pg/mL) and norepinephrine (633 +/- 285 to 443 +/- 292 pg/mL). Sauna bathing reduced the number of hospital admission for CHF (2.5 +/- 1.3 to 0.6 +/- 0.8 per year). CONCLUSION: Repeated 60 degrees C sauna bathing was safe and improved symptoms and exercise tolerance in chronic CHF patients. Sauna bathing may be an effective adjunctive therapy for chronic systolic CHF.

Very long chain N-3 fatty acids intake and carotid atherosclerosis: an epidemiological study evaluated by ultrasonography.

Epidemiological studies have shown an inverse relationship between intake of N-3 fatty acids and incidence of stroke. And, there is a high incidence of stroke in patients with carotid atherosclerosis. We investigated the relationship between intake of N-3 fatty acids and carotid atherosclerosis in the cross-sectional study. A total of 1920 Japanese, aged over 40 years, received a population-based health examination in 1999. They underwent B-mode carotid ultrasonography to evaluate the carotid intimal-medial thickness (IMT). Eating patterns were evaluated by a 105 items food frequency questionnaire. A complete data set was available for 1902 subjects (785 men and 1117 women). The mean eicosapentaenoic acid (EPA) intake in men was 0.32+/-0.23 g/day and in women was 0.31+/-0.20 g/day. The mean docosahexaenoic acid (DHA) intake in men was 0.52+/-0.34 g/day and in women was 0.49+/-0.29 g/day. With multiple linear regression analysis, after adjustments for age, sex, and total energy intake, intakes of EPA (P < 0.05), DHA (P < 0.05), and docosapentaenoic acid (P < 0.05) were significantly and inversely related to IMT. These data indicate that dietary N-3 fatty acid, especially very long chain N-3 fatty acids, may protect against carotid atherosclerosis.

Inhibition of platelet adherence to mononuclear cells by alpha-tocopherol: role of P-selectin.

BACKGROUND: Platelet-leukocyte interaction is an early important event for thrombogenesis, and this process is mainly mediated by P-selectin on platelets. Although alpha-tocopherol has been shown to inhibit thrombotic disorders, the effect of alpha-tocopherol on platelet P-selectin expression and platelet-leukocyte interaction is little known. METHODS AND RESULTS: We examined whether alpha-tocopherol inhibited human platelet P-selectin expression and platelet-leukocyte interaction. Alpha-tocopherol (50 to 500 microg/mL) inhibited thrombin-induced or phorbol 12-myristate 13-acetate (PMA)-induced P-selectin expression on platelets. alpha-Tocopherol suppressed platelet-mononuclear cell (MNC) interaction, platelet aggregation, and platelet protein kinase C (PKC) activity stimulated with either PMA (100 nmol/L) or thrombin. Inhibitory actions of alpha-tocopherol against the platelet functions were mimicked by staurosporine, a selective PKC inhibitor. After oral supplementation of alpha-tocopherol (300 mg/d for 3 weeks) in healthy subjects, thrombin-mediated or PMA-mediated P-selectin expression, platelet-MNC interaction, and platelet aggregation ex vivo were suppressed. CONCLUSIONS: alpha-Tocopherol inhibited P-selectin expression on human platelets and thereby attenuated platelet-MNC interactions, which were mediated at least in part by the inhibition of intraplatelet PKC activity. These actions of alpha-tocopherol on platelet functions provide new insights into the antithromboatherogenic properties of alpha-tocopherol.

Rescue of hypercholesterolemia-related impairment of angiogenesis by oral folate supplementation.

OBJECTIVES: We examined whether oral folate supplementation would rescue a hypercholesterolemia (HC)-related impairment of ischemia-induced angiogenesis. BACKGROUND: Folate protects against endothelial dysfunction, but the effect of folate supplementation on angiogenesis is little known. METHODS: Sprague-Dawley rats were divided into four groups. Control rats were fed a normal diet (n = 18); HC rats (n = 18) were fed 2% cholesterol diet; and HC + folate (HC+F) rats were fed an HC diet with oral folate (0.003% in water). The left femoral artery and vein were surgically excised, and angiogenesis in the ischemic limb was evaluated. We also examined the effects of Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on angiogenesis in the HC+F state. RESULTS: Laser Doppler blood flow (LDBF) analysis showed lower ischemic/normal LDBF ratio in the HC group than in the control group. Angiographic and histologic analyses on day 14 revealed a smaller angiographic score (p < 0.001) and capillary density (p < 0.001) in the HC group than in controls, which were associated with reduced tissue NOx and cyclic guanosine monophosphate (cGMP) levels. The LDBF ratio, angiographic score, and capillary density were significantly restored in the HC+F group (p < 0.01 vs. HC), which were associated with increased serum folate and tissue NOx and cGMP levels. Finally, L-NAME treatment abolished the beneficial action of folate on angiogenesis in the HC state. CONCLUSIONS: Ischemia-induced angiogenesis was inhibited by HC, which was rescued by oral folate supplementation, at least in part, via an NO-dependent manner.

P wave signal-averaged electrocardiography predicts recurrence of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome who underwent successful catheter ablation: a prospective study.

INTRODUCTION: Paroxysmal atrial fibrillation (PAF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. Catheter ablation of the accessory pathway eliminates PAF in some patients, but PAF frequently recurs in other patients. The present study was designed to determine prospectively whether P wave signal-averaged electrocardiography (P-SAECG) predicts the recurrence of PAF after successful ablation in patients with WPW syndrome. METHODS AND RESULTS: Forty-six patients with WPW syndrome who had episodes of PAF were prospectively followed. SAECG recording was performed on day 7 after successful ablation of the accessory pathway at study entry. Abnormal P-SAECG for the prediction of recurrence of PAF was defined as a filtered P wave duration > 130 msec. Eleven patients had an abnormal P-SAECG (group 1), whereas 35 patients (group 2) did not. The two groups did not differ in terms of gender, age, left atrial dimension, and atrial vulnerability as determined by electrophysiologic study. During follow-up (40 +/- 19 months), the recurrence of PAF was noted in 10 (91%) of 11 patients in group 1, whereas it was observed in only 2 (6%) of 35 patients in group 2. Kaplan-Meier analysis revealed that the recurrence of PAF was significantly more frequent in group 1 than in group 2 (log rank test, P < 0.0001). By multivariate analysis, filtered P wave duration >130 msec was an independent predictor of recurrence of PAF after ablation (Chi-square = 21.5, P < 0.0001). CONCLUSION: The results of this study indicate that P-SAECG may be useful for identifying patients at risk for recurrence of PAF after successful ablation of WPW syndrome.