Contemplative meditation reduces ambulatory blood pressure and stress-induced hypertension: a randomized pilot trial

A total of 52 pharmacologically untreated subjects with essential hypertension were randomly allocated to either 8 weeks of contemplative meditation combined with breathing techniques (CMBT) or no intervention in this observer-blind controlled pilot trial. CMBT induced clinically relevant and consistent decreases in heart rate, systolic and diastolic blood pressure if measured during office readings, 24-h ambulatory monitoring and mental stress test. Longer-term studies should evaluate CMBT as an antihypertensive strategy.     

Verapamil 240 SR versus verapamil 120 SR in arterial hypertension. A randomized double-blind,placebo-controlled study with 24-hour ambulatory blood pressure monitoring

Summary Fifteen patients (6 males, 9 females), age range 36–70 years, were enrolled in a randomized, double-blind, placebo-controlled study according to a Latin-square design, with the aim of comparing 24-hour blood pressure profiles after three 15-day treatment periods with placebo, verapamil SR 120 mg (V120 SR) given twice daily (bid), and verapamil SR 240 mg (V240 SR) given once daily (od.) All of the patients were diagnosed as mild or moderate essential hypertensives on the basis of standard casual recordings. Noninvasive 24-hour ambulatory blood pressure (BP) monitoring was performed with an ICR Spacelab 5200 automatic device. In comparison with placebo, a clinically and statistically significant reduction in both systolic and diastolic BP over 24 hours was obtained with both active treatments. Comparison of the two active treatments shows that V240 SR led to a greater reduction in systolic and diastolic BP than V120 SR. No changes in heart rate were observed. Both treatments were well tolerated. In conclusion, both verapamil regimens proved to be effective and safe in treating essential hypertensives, with V240 SR giving better 24-hour BP control.     

Transdermal clonidine in mild hypertension. A randomized, double-blind, placebo-controlled trial

In 30 patients with mild essential hypertension, clonidine hydrochloride was delivered from a skin patch reservoir designed to release medication at a constant rate for seven days. After a four-week washout period, patients were randomized (double-blind) into a clonidine- or a placebo-treated group. Clonidine or placebo was then given for five weeks, followed by a two-week washout period to assess withdrawal from treatment. Blood pressure was controlled in 11 of 15 clonidine-treated patients but in only four of 15 placebo-treated patients. The clonidine-treated group evidenced larger decreases in both systolic and diastolic blood pressures. In the clonidine-treated group, blood pressures and plasma clonidine levels were stable throughout a representative seven-day period. Besides mild skin irritation with both clonidine and placebo patches, few side effects were observed. After discontinuation of clonidine administration, plasma levels declined in a non-log linear manner. There was no rebound hypertension. The results suggest that clonidine delivered transdermally is safe and effective for control of mild essential hypertension.     

Low-dose flunitrazepam for conscious sedation for EGD: a randomized double-blind placebo-controlled study

BACKGROUND: EGD with conscious sedation is a safe procedure, but complications such as hypoxia can occur. The efficacy and safety of low-dose flunitrazepam (0.25 mg) was compared with a standard dose of flunitrazepam (0.5 mg) for moderate sedation during EGD. METHODS: In a randomized, double-blind, placebo-controlled trial, 75 outpatients (40 men, 35 women, mean age 45 [11] years) undergoing screening EGD were randomly assigned to one of 3 treatment arms: 0.25 mg of flunitrazepam (F0.25 group), 0.5 mg of flunitrazepam (F0.5 group), or placebo (normal saline solution), each administered intravenously. Patient tolerance was scored by using self-assessment questionnaires with visual analogue scales. Cardiopulmonary complications were assessed by monitoring blood pressure, heart rate, oxygen saturation, and the electrocardiogram during the procedure. RESULTS: The patient tolerance scores in the F0.25 and F0.5 groups, respectively 2.1 (2.1) and 2.3 (2.5), were significantly lower than that for the placebo group (6.5 [3.0]); there was no significant difference between F0.25 and F0.5. Cardiopulmonary complications in the F0.25 group were significantly lower than in the F0.5 group. Oxygen desaturation (oxygen saturation < 90%) was noted in two of 25 patients in the F0.5 group. Post-procedure drowsiness was observed in two of 24 (8.3%) patients in the F0.25 group and 3 of 21 (14.3%) in the F0.5 group (p = 0.2438). CONCLUSIONS: Patient tolerance of EGD with low-dose flunitrazepam (0.25 mg intravenously) was similar to that with a standard dose (0.5 mg intravenously) and significantly better than in the placebo group. Oxygen desaturation was observed only in the group that received the standard dose, suggesting that sedation with low-dose flunitrazepam is efficacious and safe for EGD.     

Melatonin reduces lung oxidative stress in patients with chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled study

Abstract: Chronic obstructive pulmonary disease (COPD), a major cause of death and disability, is attributed to an abnormal inflammatory response by the lungs to noxious substances, primarily from cigarette smoke. Although oxidative stress is regarded as central to the pathogenesis of COPD, very few studies have examined the effects of antioxidants in this condition. This was a randomized, double‐blind, placebo‐controlled study on the effects of melatonin in COPD. Thirty‐six consecutive patients with clinically stable moderate to very severe COPD (30 men; mean ± S.D. = 66.6 ± 7.8 yr) were randomized to receive 3 mg melatonin (N = 18) or placebo for 3 months. Oxidative stress was evaluated by 8‐isoprostane levels in exhaled breath condensate at baseline (T0) and after one (T1), two (T2), and three months (T3) of treatment. Additionally, exhaled breath condensate levels of IL‐8, dyspnea severity (Medical Research Council scale), lung function (spirometry), and functional exercise capacity (six min walk test) were compared at baseline and after treatment. Patients receiving melatonin showed a decrease in 8‐isoprostane (T0: mean ± S.E.M. = 20.41 ± 2.92 pg/mL; T1: 18.56 ± 2.68 pg/mL; T2: 12.68 ± 2.04 pg/mL; T3: 12.70 ± 2.18 pg/mL; P = 0.04; repeated measures ANOVA) with significant differences from baseline after 2 (P = 0.03) and 3 months (P = 0.01). Dyspnea was improved by melatonin (P = 0.01), despite no significant changes in lung function or exercise capacity. Placebo‐treated patients, but not those who were given melatonin, showed an increase in IL‐8 (P = 0.03). In summary, melatonin administration reduced oxidative stress and improved dyspnea in COPD. Further studies are necessary to determine the potential role for melatonin in the long‐term management of these patients.     

A placebo-controlled,randomized, double-blind study of OPC-8212 in patients with mild chronic heart failure

Summary OPC-8212 is a newly synthesized, orally effective inotropic agent. Previous studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure. However, the long-term efficacy of this agent remains to be established. Eighty-three patients with chronic heart failure were randomly assigned to treatment with either OPC-8212 (n=45) or matching placebo (n-38).Of the placebo-treated patients, two patients died and another six patients were withdrawn from the study because of a deterioration of heart failure, while only 1 out of 45 OPC-8212-treated patients were withdrawn because of increased congestive symptoms.After 12 weeks of treatment, the OPC-8212 group showed a significant improvement in their numerical scores in sense of well-being as judged by the patients' subscale A (p<0.01) and their physician's general impression of the patients' status (p<0.01). The ejection fraction obtained from echocardiography increased from a mean (±SEM) baseline value of 42.8±2.6% to 46.6±2.9% (p<0.05) in the OPC-8212 group and 44.4±3.7% to 45.5±4.1% in the placebo group. These effects were not associated with an increase in the heart rate. The treatment was well tolerated without any limiting side effects.Thus, OPC-8212 is effective in patients with chronic heart failure, providing significant hemodynamic and symptomatic benefit in chronic treatment, together with a possible improvement of the prognosis of patients with heart failure.     

Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study

A number of studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure treated with angiotensin converting-enzyme inhibitors. The long-term efficacy of the oral long-acting converting-enzyme inhibitor enalapril remains to be established in controlled studies. We evaluated this drug in 36 patients with New York Heart Association functional class II to III heart failure who were clinically stable on digoxin and diuretic therapy. After baseline assessment of symptoms, exercise capacity, and results of echocardiographic examination and right heart catheterization, patients were randomly assigned to treatment with 5 mg enalapril twice daily (n = 18) or placebo (n = 18) in a double-blind fashion. The two groups had similar clinical, echocardiographic, and hemodynamic characteristics before treatment. After 3 months of treatment, the enalapril group showed a significant improvement as judged by subjective patient impression, functional class, and exercise duration (9.3 +/- 5.7 vs 17.6 +/- 5.6 min; p less than .001). Diuretic dosage was reduced in six patients and increased in one patient, one patient had died and another had been withdrawn from the study. In the placebo group there was no significant change with respect to patient impression, functional class, or exercise duration; diuretic dosage was increased in seven patients and four patients had died. Echocardiographic left ventricular dimensions were significantly reduced and left ventricular shortening fraction significantly increased in the enalapril group but were unchanged in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy and safety of darusentan in patients with resistant hypertension: results from a randomized, double-blind, placebo-controlled dose-ranging study

In this phase 2, randomized, double-blind, placebo-controlled forced dose-titration study, 115 patients with resistant hypertension, receiving background therapy with ≥3 antihypertensive medications including a diuretic at full doses, were randomized 2:1 to increasing doses of darusentan (10, 50, 100, 150, and 300 mg), a selective endothelin receptor antagonist, or matching placebo once daily for 10 weeks. Darusentan treatment decreased mean systolic and diastolic blood pressure levels in a dose-dependent fashion compared with placebo; the largest reductions were observed at week 10 (300-mg dose) (systolic, −11.5±3.1 mm Hg [ P =.015]; diastolic, −6.3±2.0 mm Hg [ P =.002]). Darusentan (300 mg) also decreased mean 24-hour, daytime, and nighttime ambulatory blood pressures from baseline to week 10. Darusentan was generally well tolerated; mild to moderate edema and headache were the most common adverse events. This study demonstrates a clinical benefit from a new class of antihypertensive agent in patients classified as resistant by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines.     

Effects of anthocyanins on blood pressure and stress reactivity: a double-blind randomized placebo-controlled crossover study

High intakes of flavonoids are associated with reduced cardiovascular risk, and flavonoids such as cocoa and soy protein isolate have shown beneficial effects on blood pressure (BP). Anthocyanins constitute a flavonoid subgroup consumed in regular diets, but few studies have assessed the antihypertensive potential of anthocyanins. We aimed to assess whether high concentrations of relatively pure anthocyanins reduce BP and alter cardiovascular and catecholamine reactivity to stress. A total of 31 healthy men between 35-51 years of age with screening BP >140/90 mm Hg, not on antihypertensive or lipid-lowering medication, were randomised in a double-blind crossover study to placebo versus 320-mg anthoycanins twice daily. Treatment duration was 4 weeks, with a 4-week washout. Sitting and supine BP measurements, ambulatory BP recording and stress reactivity were assessed and analyzed by a paired sample t-test. In all, 27 patients completed all visits. Sitting systolic BP (primary endpoint) was 133 mm Hg after placebo versus 135 mm Hg after anthocyanin treatment (P=0.25). Anthocyanins did neither affect semiautomatic oscillometric BP measurements in the sitting or supine position nor 24-h ambulatory BP. No significant differences in stress reactivity were found across treatment periods. Overall, we conclude that high concentrations of these relatively pure anthocyanins do not reduce BP in healthy men with a high normal BP.     

Differences in ambulatory blood pressure between men and women with mild hypertension

Non-invasive ambulatory blood pressure monitoring was performed in a consecutive series of 87 subjects with recently detected mild uncomplicated hypertension. Obese subjects, diabetics and those with secondary hypertension were excluded. Ambulatory pressures were recorded on a day of usual activity. Average ambulatory systolic and diastolic pressures were significantly lower than referral pressures determined in clinics or screening sites and initial pressures taken by the monitors. Whereas men (57) and women (30) had similar referral and initial pressures, average ambulatory systolic pressure was significantly higher in men; diastolic pressure was not different. Men also had a significantly higher fraction of ambulatory systolic pressures greater than 140 mmHg compared to women. Fifty-six percent of the men and 80% of the women had average ambulatory systolic pressures less than 140 mmHg and diastolic pressures less than 90 mmHg; the difference between the sexes was significant (chi 2 = 6.99, P less than 0.01). Thus, in mild hypertension, women have lower average systolic pressure than men during ordinary daily activity. These results may account for lower long-term cardiovascular morbidity in hypertensive women compared with men.     

The application of nebivolol in essential hypertension: a double-blind, randomized, placebo-controlled study.

This randomized, double-blind, placebo-controlled study investigated the effects of nebivolol on blood pressure, plasma renin and vasoactive hormones (aldosterone and atrial natriuretic peptide) and the heart (arrhythmias, left ventricular mass and ejection fraction) in 32 hypertensive Chinese patients aged 25-65 years. Patients received either placebo (3 men, 11 women) or nebivolol 5 mg (5 men, 13 women) once daily for 4 weeks. In the nebivolol group, a significant decrease in blood pressures (P less than 0.001) and heart rate (P less than 0.01) was seen. Nebivolol therapy also suppressed plasma renin and aldosterone concentration (P less than 0.02) but increased plasma atrial natriuretic peptide levels (P less than 0.03). No significant changes in routine blood biochemistry were demonstrated in either group. There was a tendency for left ventricular mass to decline, and left ventricular ejection fraction to rise during nebivolol therapy, but these changes did not reach statistical significance. There was no significant change in ectopic activity. None of the 32 subjects had adverse experiences requiring cessation of therapy. In conclusion, nebivolol in a dose of 5 mg daily is effective and well tolerated in patients with essential hypertension. It suppresses plasma renin and aldosterone and stimulates plasma atrial natriuretic peptide.     

轻中度高血压患者血压达标后动态血压及血压节律的变化特点

目的探讨轻中度高血压患者血压达标后动态血压及血压节律的变化特点。方法选择124名轻中度高血压患者,给予口服厄贝沙坦/氢氯噻嗪复方制剂（每片含厄贝沙坦150mg及氢氯噻嗪12.5mg）控制血压,目标血压值为〈130/85mmHg（1mmHg=0.133kPa）,根据血压达标情况增加药物剂量,观察时间为14～16d。记录血压达标患者治疗前后动态血压参数及血压达标所需时间。结果治疗后共70例患者血压达标,血压达标患者24h收缩压（SBP）,24h舒张压（DBP）,昼间平均SBP,昼间平均DBP,夜间平均SBP,夜间平均DBP及脉压在治疗前后差异均有统计学意义（P均〈0.05）。治疗后血压达标患者的血压节律构成比发生变化,正常血压节律患者的比例由治疗前52.8%增加至治疗后的81.4%,治疗前后血压节律构成比的差异有统计学意义（P〈0.05）。血压达标患者中血压节律正常者与血压节律异常者血压达标所需天数分别为[（7.70±2.20）dvs.（9.21±2.63）d],差异有统计学意义（P〈0.05）。结论厄贝沙坦/氢氯噻嗪复方制剂降低轻中度高血压患者血压的同时,改善了血压达标患者的昼夜血压节律。     

Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind,placebo-controlled study

Hypertension is often associated with insulin resistance, dyslipidemia and obesity, which indicate a prediabetic state and increased risk of cardiovascular disease. Pioglitazone treatment of patients with type 2 diabetes reduces insulin resistance and improves lipid profiles. The present double-blind placebo-controlled study is the first study to report effects of pioglitazone in non-diabetic patients with arterial hypertension. Following a one week run-in, 60 patients were randomized to receive either pioglitazone (45 mg/day) or placebo for 16 weeks. Insulin sensitivity (M-value) increased by 1.2 +/- 1.7 mg/min/kg with pioglitazone compared with 0.4 +/- 1.4 mg/min/kg (P = 0.022) with placebo. HOMA index was decreased (-22.5 +/- 45.8) by pioglitazone but not by placebo (+0.8 +/- 26.5; P < 0.001). Decreases in fasting insulin and glucose were significantly (P = 0.002 and P = 0.004, respectively) greater with pioglitazone than placebo. Body weight did not change significantly with either treatment. HDL-cholesterol was increased and apolipoprotein B was decreased to a significantly greater extent with pioglitazone. There was a significantly (P = 0.016) greater decrease from baseline in diastolic blood pressure with pioglitazone. These changes would suggest improved glucose metabolism and a possible reduction in risk of cardiovascular disease with pioglitazone treatment of non-diabetic patients with arterial hypertension.     

A randomized, double-blind, placebo-controlled parallel-group study to assess the efficacy and safety of nebivolol, a novel beta-blocker, in patients with mild to moderate hypertension

This double-blind, multicenter, randomized placebo-controlled study evaluated the antihypertensive efficacy and safety of nebivolol, a selective beta1-adrenoreceptor blocker with vasodilating effects, in patients with mild to moderate hypertension (sitting diastolic blood pressure [SiDBP] > or =95 mm Hg and < or =109 mm Hg). A total of 909 patients were randomized to receive placebo or nebivolol 1.25, 2.5, 5, 10, 20, or 40 mg once daily for up to 84 days. The primary end point was the change in trough SiDBP from baseline to study end. Nebivolol significantly reduced trough SiDBP (8.0-11.2 mm Hg compared with 2.9 mm Hg with placebo; P<.001) and trough sitting systolic blood pressure (a 4.4-9.5-mm Hg decrease compared with a 2.2-mm Hg increase [corrected] with placebo; P< or =.002). The overall adverse event experience was similar in the nebivolol (46.1%) and placebo (40.7%) groups (P=.273). Once-daily nebivolol is an effective antihypertensive in mild to moderate hypertensive patients.     

Effect of dietary fiber intake on blood pressure: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To examine the effect of dietary fiber intake on blood pressure (BP). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING AND PARTICIPANTS: A total of 110 trial participants aged 30 to 65 years who had untreated, but higher than optimal BP or stage-1 hypertension were recruited from the community in New Orleans, Louisiana, USA. INTERVENTIONS: Study participants were randomly assigned to receive 8 g/day of water-soluble fiber from oat bran or a control intervention. MAIN OUTCOME MEASURES: Nine BP measurements were obtained by trained observers using random-zero sphygmomanometers, over three clinical visits, at the baseline and termination visits of the trial. An average of the nine measurements was used to determine mean BP at the baseline and termination visits. RESULTS: The net changes [95% confidence interval, (CI)] in systolic blood pressure were -1.8 mmHg (-4.3 to 0.8, P = 0.17) following 12 weeks, -2.2 mmHg (-5.3 to 1.0, P = 0.18) following 6 weeks, and -2.0 mmHg (-4.4 to 0.3, P = 0.09) for an average of the 6- and 12-week visits. The corresponding net changes (95% CI) in diastolic blood pressure were -1.2 mmHg (-3.0 to 0.5, P = 0.17) following 12 weeks, -0.8 mmHg (-3.1 to 1.4, P = 0.47) following 6 weeks, and -1.0 mmHg (-2.6 to 0.5, P = 0.19) for an average of the 6- and 12-week visits. CONCLUSIONS: Our findings suggest that a diet rich in fiber may have a moderate BP-lowering effect and indicate the need for further investigation of this important question.