Effect of the HMG-CoA reductase inhibitors on blood pressure in patients with essential hypertension and primary hypercholesterolemia

Certain hydroxymethylglutaryl coenzyme A reductase inhibitors, ie, statins, may cause vasodilation by restoring the endothelial dysfunction that frequently accompanies hypertension and hypercholesterolemia. Several studies have found that a blood pressure reduction is associated with the use of statins, but conclusive evidence from controlled trials is lacking. After an 8-week placebo and diet run-in period, 30 persons with moderate hypercholesterolemia and untreated hypertension (total cholesterol 6.29+/-0.52 mmol/L, systolic and diastolic blood pressure 149+/-6 and 97+/-2 mm Hg) were randomized in a double-blind manner to placebo or pravastatin (20 to 40 mg/d) in a crossover design. In 25 participants who completed the 32-week trial, pravastatin decreased total and LDL cholesterol (both -1.09 mmol/L, P=0.001), systolic and diastolic blood pressure (-8 and -5 mm Hg, both P=0.001), and pulse pressure (-3 mm Hg, P=0.011) and blunted the blood pressure increase caused by the cold pressor test (-4 mm Hg, P=0.005) compared with placebo. It also reduced the level of circulating endothelin-1 (P=0.001). The blood pressure results were virtually unchanged in stratified analyses according to gender and age and in intention-to-treat analyses that included the 5 patients who dropped out of the study. When the participants were taking either placebo or pravastatin, blood pressure was not significantly correlated with total or LDL cholesterol or with circulating endothelin-1. Pravastatin decreases systolic, diastolic, and pulse pressures in persons with moderate hypercholesterolemia and hypertension. This antihypertensive effect may contribute to the documented health benefits of certain statins.     

Antihypertensive effect of sustained-release isosorbide dinitrate for isolated systolic systemic hypertension in the elderly

A double-blind, randomized trial was performed in 40 patients, mean age (+/- standard deviation) 80 +/- 4 years, with isolated systolic systemic hypertension to evaluate the antihypertensive effect of oral sustained-release isosorbide dinitrate (ISDN), 20 to 40 mg twice daily, vs placebo. After 12 weeks of treatment, supine systolic blood pressure (BP) decreased from 192 +/- 10 to 162 +/- 12 mm Hg with ISDN (p less than 0.001) and from 189 +/- 10 to 175 +/- 15 mm Hg with placebo (p less than 0.001). On the basis of variance analysis, the decrease in systolic BP was significantly lower with ISDN (27 mm Hg) than with placebo (13 mm Hg). Similar results were observed for supine and erect systolic BP measured at 8 AM and 4 PM, 8 and 12 hours after drug intake. No significant differences in diastolic BP, heart rate or side effects occurred. After the ISDN tapering off-period (2 weeks), systolic BP increased significantly but did not change with placebo. The study provided evidence that in elderly patients with systolic hypertension, sustained-release ISDN induced a selective and sustained decrease in systolic BP, antihypertensive effect was observed 8 and 12 hours after drug administration, and no tolerance phenomenon was noted.     

Combination therapy with amlodipine and captopril for resistant systemic hypertension

This study was conducted to assess the therapeutic utility of combining amlodipine with captopril in patients with moderate-to-severe hypertension. Patients had hypertension of WHO grades I–III, with initial mean sitting and standing diastolic blood pressure of 100–119 mm Hg (phase V) after 2–4 weeks on placebo, and had remained uncontrolled (diastolic blood pressure > 95 mm Hg) despite a further 4 weeks on low-dose captopril. Twenty-nine patients entered the computer-randomized, double-blind, placebocontrolled, 2-way crossover comparison of either amlodipine 10 mg once daily or matching placebo added to continued therapy with captopril 25 mg twice daily for 4 weeks. Patients then acted as their own control and received the alternative amlodipine/placebo treatment plus their continued captopril therapy for another 4 weeks. Once-daily amlodipine was shown to be effective when combined with captopril. Mean baseline supine systolic blood pressure decreased from 167 to 149 mm Hg and standing systolic blood pressure from 167 to 144 mm Hg. Mean supine diastolic blood pressure decreased from 105 to 92 mm Hg, and standing diastolic blood pressure decreased from 110 to 96 mm Hg. The placebo-corrected amlodipine differences in mean changes from captopril baseline were −18/−12.2 mm Hg for supine and −20.1/−11.9 mm Hg for standing systolic and diastolic blood pressures, respectively (p < 0.001 for all 4 measurements). The most common side effects encountered with amlodipine were flushing and pedal edema. The combination of amlodipine and captopril was well tolerated, and no patient discontinued therapy. No significant treatment-related effects on biochemical and hematologic parameters were noted.     

Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina

OBJECTIVE: We sought to study the effects of a single oral dose of sildenafil citrate (50 mg) on blood pressure (BP) in men taking the nitric oxide (NO) donor drugs isosorbide mononitrate (ISMN) or glyceryl trinitrate (GTN) for stable angina. BACKGROUND: Sildenafil, a selective phosphodiesterase type 5 inhibitor, is an orally effective treatment for erectile dysfunction. The presence of phosphodiesterases in the vasculature suggests the possibility of an interaction between sildenafil and NO donor drugs. METHODS: Two double-blind, placebo-controlled, randomized, two-way crossover trials were undertaken. Sixteen male patients received oral ISMN (20 mg twice a day) for five to seven days before their dose of sildenafil or placebo and continued receiving ISMN daily until administration of the alternate drug seven days later. For the second study, 15 male patients received sublingual GTN (500 microg) 1 h after sildenafil or placebo on each of two study days, which were seven days apart. Sitting or standing BP was measured before and for 6 h after the administration of the study drug. RESULTS: The effects of sildenafil plus ISMN on BP (standing mean maximum reductions from baseline in systolic/diastolic BP, -52/-29 mm Hg) were greater than the effects of placebo plus ISMN on BP (-25/-15 mm Hg; p < 0.001). Sildenafil plus GTN also resulted in greater sitting mean maximum reductions from baseline in systolic/diastolic BP (-36/-21 mm Hg) compared with placebo plus GTN (-26/-12 mm Hg; p < 0.01). CONCLUSIONS: Coadministration of sildenafil with ISMN or GTN produced significantly greater reductions in BP than ISMN or GTN alone. Based on these data, sildenafil should not be administered to patients taking nitrates.     

Lacidipine and blood pressure variability in diabetic hypertensive patients

The aim of our study was to assess the effects of lacidipine, a long-acting calcium antagonist, on 24-hour average blood pressure, blood pressure variability, and baroreflex sensitivity. In 10 mildly to moderately hypertensive patients with type II diabetes mellitus (aged 18 to 65 years), 24-hour ambulatory blood pressure was continuously monitored noninvasively (Portapres device) after a 3-week pretreatment with placebo and a subsequent 4-week once daily lacidipine (4 mg) or placebo treatment (double-blind crossover design). Systolic blood pressure, diastolic blood pressure, and heart rate means were computed each hour for 24 hours (day and night) at the end of each treatment period. Similar assessments were also made for blood pressure and heart rate variability (standard deviation and variation coefficient) and for 24-hour baroreflex sensitivity, which was quantified (1) in the time domain by the slope of the spontaneous sequences characterized by progressive increases or reductions of systolic blood pressure and RR interval and (2) in the frequency domain by the squared ratio of RR interval and systolic blood pressure spectral power approximately 0.1 and 0.3 Hz over the 24 hours. Compared with placebo, lacidipine reduced the 24-hour, daytime, and nighttime systolic and diastolic blood pressure (P<0.05) with no significant change in heart rate. It also reduced 24-hour, daytime, and nighttime standard deviation (-19.6%, -14.4%, and -24.0%, respectively; P<0.05) and their variation coefficient. The 24-hour average slope of all sequences (7.7+/-1.7 ms/mm Hg) seen during placebo was significantly increased by lacidipine (8.7+/-1.8 ms/mm Hg, P<0.01), with a significant increase being obtained also for the 24-hour average alpha coefficient at 0.1 Hz (from 5.7+/-1.5 to 6.4+/-1.3 ms/mm Hg, P<0.01). Thus, in diabetic hypertensive patients, lacidipine reduced not only 24-hour blood pressure means but also blood pressure variability. This reduction was accompanied by an improvement of baroreflex sensitivity. Computer analysis of beat-to-beat 24-hour noninvasive blood pressure monitoring may offer valuable information about the effects of antihypertensive drugs on hemodynamic and autonomic parameters in daily life.     

Systolic time intervals as possible predictors of pressure response to sustained beta-adrenergic blockade in arterial hypertension. A within-patient, placebo-controlled study

Systolic time intervals (STI) were recorded at rest and during isometric exercise (IHG) in 20 hypertensive outpatients, WHO Stage 1 or 2. In a double-blind crossover study, slow-release metoprolol 200 mg once daily and matched placebo were given for 4 weeks each, at the end of a 2-week placebo washout. Blood pressure and STI were taken in the last day of washout and of either crossover period. Treatment decreased blood pressure and heart rate values at rest and on peak IHG; it didn't modify preejection period index (PEPI), left ventricular ejection time index (LVETI), and their ratio at rest, but decreased the ratio between diastolic blood pressure and PEPI (DBP/PEPI ratio) at rest and on peak IHG and lengthened the PEPI at peak IHG. Resting PEPI values on placebo treatment showed a negative correlation with systolic (r = -0.72) as well as diastolic (r = -0.80) pressure reduction on slow-release metoprolol as compared with placebo treatment. The PEP/LVET ratio at rest on placebo treatment showed a negative correlation with systolic (r = -0.78) as well as diastolic (r = -0.82) pressure reduction at rest on metoprolol compared with placebo treatment. Patients with a resting PEP/LVET ratio less than 0.43 showed a reduction in both systolic and diastolic pressure approximating or exceeding 20 mm Hg, whereas patients with a PEP/LVET ratio greater than 0.47 showed a decrease in systolic and diastolic blood pressure of less than 10 mm Hg. In patients with a PEP/LVET ratio of 0.43 to 0.47 (50% of the trial population), STI didn't show any correlation with the pressure response to beta-blockade. A positive correlation was found between the DBP/PEPI ratio at rest on placebo treatment and systolic (r = 0.56) as well as diastolic (r = 0.76) pressure reduction at rest on slow-release metoprolol compared with placebo treatment. Thus, STI appeared as promising predictors of the magnitude of blood pressure response to sustained beta-blocking therapy in mild-to-moderate essential hypertension, mostly in patients with a resting PEP/LVET ratio less then 0.43 or greater then 0.47.     

Treatment of essential hypertension with PN 200-110 (isradipine)

The safety and antihypertensive efficacy of PN 200-110 (isradipine), a novel calcium antagonist, are discussed in a preliminary report of double-blind, multicenter, controlled, phase III clinical trials for essential hypertension. Patients who qualified for entry after a 3 week placebo-washout period were enrolled in 1 of 5 studies; 2 studies were placebo controlled; 3 studies evaluated PN 200-110 against 1 of 3 active controls: hydrochlorothiazide (HCTZ) propranolol or prazosin. A separate study assessing the effects of PN 200-110 in combination with HCTZ versus propranolol plus HCTZ is also discussed. Compared with placebo, PN 200-110 decreased mean supine systolic and diastolic blood pressures by 20/16 mm Hg versus 4/6 mm Hg. Compared with placebo and active control drugs, PN 200-110 normalized supine diastolic blood pressure to less than or equal to 90 mm Hg in 72% of patients, versus 13% in the placebo group, 74% in the HCTZ group, 45% in the propranolol group and 69% in the prazosin group. In the ability to decrease diastolic blood pressure by greater than or equal to 10 mm Hg, PN 200-110 compared favorably to prazosin (81% vs 81%), and was superior to HCTZ (81% vs 61%) and propranolol (81% vs 36%). In combination with HCTZ, PN 200-110 exerted as great an antihypertensive effect as propranolol plus HCTZ. Long-term therapy with PN 200-110 was also effective. Supine systolic and diastolic blood pressures decreased a mean of 15/13 mm Hg at 3 months, and 18/20 mm Hg at 12 months. PN 200-110 is well tolerated with relatively few adverse effects reported.     

Double-blind comparison of ketanserin with placebo in patients with essential hypertension

Two double-blind multicenter trials were performed to compare the antihypertensive action of ketanserin, at an oral dosage of 20 mg three times daily, with that of placebo over a period of four to six weeks. A subset of patients was treated in a crossover fashion for either four weeks (36 patients) or six weeks (24 patients). The patients had essential hypertension, with a diastolic blood pressure greater than or equal to 95 mmHg measured in sitting position at the end of a placebo run-in period of at least one week. In a first trial, 78 of 82 patients completed the four-week study period, where the mean drop of the systolic/diastolic blood pressure was -14/-12 mmHg in the ketanserin group (n = 32) versus -8/-5 mmHg in the placebo group (n = 46). This difference is statistically significant (p = 0.05/p less than 0.01). In 13 patients who after the initial ketanserin treatment were further treated with placebo in crossover for four weeks, the blood pressure rose slightly (+1/+3 mmHg). In the alternative group (n = 23), the blood pressure fell by -10/-7 mmHg after placebo and decreased further by -10/-8 mmHg after ketanserin. In a second trial, 24 patients completed a two by six week crossover treatment. In 12 patients assigned to the sequence placebo-ketanserin, there was a drop of the systolic/diastolic blood pressure by -7/-4 mmHg after placebo and an additional drop by -26/-10 mmHg after ketanserin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients

The aim of this study was to assess the effect of valsartan addition to amlodipine on ankle foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. After a 4-week placebo period, 80 grade 1-2 hypertensive patients (diastolic blood pressure (DBP)>90 mm Hg and <110 systolic blood pressure (SBP)>140 mm Hg) were randomized to amlodipine 10 mg or valsartan 160 mg or amlodipine 10 mg plus valsartan 160 mg for 6 weeks according to an open-label, blinded end point, crossover design. At the end of the placebo period and of each treatment period, blood pressure, AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed connecting the subcutaneous pretibial interstitial environment with a water manometer. Both amlodipine and valsartan monotherapy significantly reduced SBP (-16.9 and -14.5 mm Hg, respectively, P<0.01 vs baseline), and DBP (-12.9 and -10.2 mm Hg, respectively, P<0.01 vs baseline) but the reduction was greater with the combination (-22.9 mm Hg for SBP, P<0.01 vs monotherapy; -16.8 mm Hg for DBP, P<0.01 vs monotherapy). Amlodipine monotherapy significantly increased both AFV (+23%, P<0.01 vs baseline) and PSTP (+75.5%, P<0.001 vs baseline) whereas valsartan monotherapy did not influence them. As compared to amlodipine alone, the combination produced a less marked increase in AFV (+6.8%, P<0.01 vs amlodipine) and PSTP (+23.2%, P<0.001 vs amlodipine). Ankle oedema was clinically evident in 24 patients with amlodipine and in six patients with the combination. These results suggest that angiotensin receptor blockers partially counteract the microcirculatory changes responsible for calcium channel blockers induced oedema formation.     

Effect of regular phosphodiesterase type 5 inhibition in hypertension

There are no published controlled clinical trials of regular phosphodiesterase type 5 inhibitor therapy as a long-term treatment of hypertension. In a randomized, double-blind, 2-way crossover study, 25 otherwise untreated hypertensive subjects were administered 50 mg of sildenafil or matched placebo 3 times daily for 16 days, and the effects on ambulatory blood pressure (BP), clinic BP, arterial wave reflection, carotid-femoral pulse wave velocity, and brachial artery flow-mediated dilatation were assessed. Three subjects were withdrawn because of adverse effects, and the data from the remaining 22 subjects were analyzed. Sildenafil reduced ambulatory BP (mean [SE] change from baseline for average daytime BP: systolic -8 [2] mm Hg versus 2 [2] mm Hg with placebo, P<0.01; diastolic -6 [1] mm Hg versus 0 [1] mm Hg, P<0.01) and clinic BP (change from baseline to 1 hour after drug administration on day 16: systolic -5 [2] mm Hg versus 4 [2] mm Hg, P<0.01; diastolic -5 [1] mm Hg versus 2 [2] mm Hg, P<0.01). Compared with baseline, sildenafil, but not placebo, reduced arterial wave reflection both acutely and after chronic treatment, but the chronic change in arterial wave reflection was not statistically different from the chronic change with placebo. Sildenafil did not affect pulse wave velocity or flow-mediated dilatation. The main adverse effects of sildenafil, which were generally transient and rated as mild or moderate in severity, were dyspepsia, headache, and myalgia. In conclusion, regular sildenafil constitutes effective antihypertensive therapy. Further studies are warranted to evaluate the role of longer-acting phosphodiesterase type 5 inhibitors as antihypertensive agents in clinical practice.     

Pulse pressure changes with six classes of antihypertensive agents in a randomized, controlled trial

Pulse pressure has been more strongly associated with cardiovascular outcomes, especially myocardial infarction and heart failure, than has systolic, diastolic, or mean arterial pressure in a variety of populations. Little is known, however, of the comparative effects of various classes of antihypertensive agents on pulse pressure. In retrospective analyses of the Veterans Affairs Single-Drug Therapy for Hypertension Study, we compared changes in pulse pressure with 6 classes of antihypertensive agents: 1292 men with diastolic blood pressure of 95 to 109 mm Hg on placebo were randomized to receive hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, prazosin, or placebo. Drug doses were titrated to achieve a goal diastolic blood pressure of <90 mm Hg during a 4- to 8-week medication titration phase. Pulse pressure change (placebo subtracted) was assessed from baseline to the end of the 3-month titration and 1-year maintenance. Mean baseline systolic, diastolic, and pulse pressures were 152, 99, and 53 mm Hg, respectively. Reductions in pulse pressure during titration were greater (P<0.001) with clonidine (6.7 mm Hg) and hydrochlorothiazide (6.2 mm Hg) than with captopril (2.5 mm Hg), diltiazem (1.6 mm Hg), and atenolol (1.4 mm Hg); reduction with prazosin (3.9 mm Hg) was similar to all but clonidine. After 1 year, pulse pressure was reduced significantly more (P<0.001) with hydrochlorothiazide (8.6 mm Hg) than with captopril and atenolol (4.1 mm Hg with both); clonidine (6.3 mm Hg), diltiazem (5.5 mm Hg), and prazosin (5.0 mm Hg) were intermediate. These data show that classes of antihypertensive agents differ in their ability to reduce pulse pressure. Whether these differences affect rates of cardiovascular events remains to be determined.     

Effect of soy isoflavones on blood pressure: a meta-analysis of randomized controlled trials

Background and aimThe effect of soy isoflavones on blood pressure is controversial. The objective of this study was to evaluate the effect of dietary soy isoflavones on blood pressure.Methods and ResultsTrials were searched in PubMed, the Cochrane Library, Embase and references cited in related reviews and studies. A total of eleven trials were reviewed. Meta-analysis results showed a mean decrease of 2.5 mm Hg (95% CIs, ? 5.35 to 0.34 mm Hg; P = 0.08) for systolic blood pressure and 1.5 mm Hg (95% CIs, ? 3.09 to 0.17 mm Hg; P = 0.08) for diastolic blood pressure in the soy isoflavones-treated group compared to placebo. Meta-regression and subgroup analyses indicated that blood pressure status was a significant predictor of heterogeneity for the effect of soy isoflavones on blood pressure. Subgroup analysis of hypertensive subjects revealed that a greater blood pressure reduction was identified in the soy isoflavone-treated group compared to placebo (5 trials; SBP: ? 5.94, 95% CIs [? 10.55, ? 1.34] mm Hg, P = 0.01; DBP: ? 3.35, 95% CIs [- 6.52, ? 0.19] mm Hg, P = 0.04). In contrast, treatment with soy isoflavones did not lead to a significant reduction in blood pressure in normotensive subjects (6 trials; SBP: 0.29, 95% CIs [- 2.39, 2.97] mm Hg, P = 0.83; DBP: ? 0.43, 95% CIs [- 1.66, 0.81] mm Hg, P = 0.50).ConclusionSoy isoflavones had an effect of lowering blood pressure in hypertensive subjects, but not in normotensive subjects. Larger trials need to be carried out to confirm the present findings.     

Effect of endurance training on blood pressure at rest, during exercise and during 24 hours in sedentary men

The effect of 4 months of physical training on resting, exercise and 24-hour blood pressure (BP) was studied using a randomized crossover design in 26 healthy, sedentary men, with an average age of 39 +/- 10 (standard deviation) years. Peak oxygen uptake increased by 14% (p less than 0.001) and the physical working capacity at a heart rate of 130 beats/min by 25% (p less than 0.001). The heart rate was reduced by 7 beats/min at night (p less than 0.01) and by 6 beats/min during the day (p less than 0.001). Training-induced changes of BP varied according to measuring conditions. A decrease in BP at rest while sitting in the morning in the laboratory was significant for diastolic (-5 mm Hg, p less than 0.01) but not for systolic BP. During exercise, systolic BP was significantly lower after training, when measured at the same submaximal workloads. However, when workload was expressed as a percentage of peak oxygen uptake, systolic BP was not different before and after training. When measured during 24 hours, the training-induced change in BP was not significant at night either for systolic or diastolic BP. During the day the decrease in diastolic BP was significant (-5 mm Hg, p less than 0.001), but the change in systolic BP was not.     

Effect of cocoa and tea intake on blood pressure: a meta-analysis

BACKGROUND: Epidemiological evidence suggests blood pressure-lowering effects of cocoa and tea. We undertook a meta-analysis of randomized controlled trials to determine changes in systolic and diastolic blood pressure due to the intake of cocoa products or black and green tea. METHODS: MEDLINE, EMBASE, SCOPUS, Science Citation Index, and the Cochrane Controlled Trials Register were searched from 1966 until October 2006 for studies in parallel group or crossover design involving 10 or more adults in whom blood pressure was assessed before and after receiving cocoa products or black or green tea for at least 7 days. RESULTS: Five randomized controlled studies of cocoa administration involving a total of 173 subjects with a median duration of 2 weeks were included. After the cocoa diets, the pooled mean systolic and diastolic blood pressure were -4.7 mm Hg (95% confidence interval [CI], -7.6 to -1.8 mm Hg; P = .002) and -2.8 mm Hg (95% CI, -4.8 to -0.8 mm Hg; P = .006) lower, respectively, compared with the cocoa-free controls. Five studies of tea consumption involving a total of 343 subjects with a median duration of 4 weeks were selected. The tea intake had no significant effects on blood pressure. The estimated pooled changes were 0.4 mm Hg (95% CI, -1.3 to 2.2 mm Hg; P = .63) in systolic and -0.6 mm Hg (95% CI, -1.5 to 0.4 mm Hg; P = .38) in diastolic blood pressure compared with controls. CONCLUSION: Current randomized dietary studies indicate that consumption of foods rich in cocoa may reduce blood pressure, while tea intake appears to have no effect.     

Self-measurement of blood pressure at home reduces the need for antihypertensive drugs: a randomized, controlled trial

It is still uncertain whether one can safely base treatment decisions on self-measurement of blood pressure. In the present study, we investigated whether antihypertensive treatment based on self-measurement of blood pressure leads to the use of less medication without the loss of blood pressure control. We randomly assigned 430 hypertensive patients to receive treatment either on the basis of self-measured pressures (n=216) or office pressures (OPs; n=214). During 1-year follow-up, blood pressure was measured by office measurement (10 visits), ambulatory monitoring (start and end), and self-measurement (8 times, self-pressure group only). In addition, drug use, associated costs, and degree of target organ damage (echocardiography and microalbuminuria) were assessed. The self-pressure group used less medication than the OP group (1.47 versus 2.48 drug steps; P<0.001) with lower costs ($3222 versus $4420 per 100 patients per month; P<0.001) but without significant differences in systolic and diastolic OP values (1.6/1.0 mm Hg; P=0.25/0.20), in changes in left ventricular mass index (-6.5 g/m(2) versus -5.6 g/m(2); P=0.72), or in median urinary microalbumin concentration (-1.7 versus -1.5 mg per 24 hours; P=0.87). Nevertheless, 24-hour ambulatory blood pressure values at the end of the trial were higher in the self-pressure than in the OP group: 125.9 versus 123.8 mm Hg (P<0.05) for systolic and 77.2 versus 76.1 mm Hg (P<0.05) for diastolic blood pressure. These data show that self-measurement leads to less medication use than office blood pressure measurement without leading to significant differences in OP values or target organ damage. Ambulatory values, however, remain slightly elevated for the self-pressure group.     

Placebo: its hypotensive effect and influence on certain psychological parameters and dependency on dosage prescribed to patients

The main purpose of this study is to estimate the influence of taking a number of placebo tablets to obtain hypotensive effects and some psychological parameters with essential hypertension. 197 patients (102F/95M) aged between 18-80 years (average age 52.3) with essential hypertension were included in the research in two outpatients clinics. The patients who participated in research, stayed for at least seven days without any pharmacological treatment. They had a diastolic pressure (DBP) between 95-114 mm Hg and systolic pressure (SBP) up to 200 mm Hg. 92 patients had taken one tablet a day and 105 patients had taken two tablets in the morning. This was before the placebo was included and two weeks after their blood pressure had been taken by standard methods (sphygmomanometer). They were monitored daily throughout the period using traditional methods and ABPM (SpaceLabs 90121). The patients completed two psychological tests. 97 records (52F/45M) qualified for statistical analysis (80% of measurements were undertaken properly, and the time between measurements was less than two hours). Psychological questionnaires were correctly completed by 92 patients. The visible results of decreasing systolic and diastolic value of blood pressure were obtained after using one (group 1) and two (group 2) placebo tablets. They were monitored by a standard method and recorded by ABPM. In group 1 SBP decreased from 164 +/- 11.4 mm Hg to 158 +/- 8.8 mm Hg (p < 0.01, on standard method) and from 149.5 +/- 17.8 to 144.5 +/- 8.3 mm Hg daily (p < 0.05, ABPM). DBP in this examined group decreased from 106.2 +/- 2.8 to 102 +/- 3.9 mm Hg (p < 0.01, stand. method), and from 103.2 +/- 2.6 to 98.6 +/- 1.2 mm Hg daily (p < 0.05, ABPM). In the second group SBP decreased from 169 +/- 12.8 to 157.6 +/- 17.9 mm Hg (p < 0.001, stand. method), and in ABPM from 148.5 +/- 15.8 to 139.6 +/- 16.2 mm Hg (p < 0.01). In this same group, DBP decreased from 104.4 +/- 2.6 to 98 +/- 3.4 mm hG (p < 0.001, stand. method), and from 107.4 +/- 5.8 mm Hg to 95.5 +/- 4.2 mm Hg-daily (p < 0.001, ABPM). There were no differences between heart rate in all groups of patients. In both groups there were significant statistical differences in negative symptoms, physical symptoms and anexity, but a more optimistic mood was observed by group 2. More effective hypertensive treatment was observed within the group which was treated with two placebo tablets. This group was characterized by more optimistic mood compared to the group which was treated with one placebo tablet a day.     

Results of the Diet,Exercise, and Weight Loss Intervention Trial (DEW-IT)

National guidelines for the prevention and treatment of hypertension recommend sodium reduction, weight loss, the Dietary Approach to Stop Hypertension (DASH) diet, and regular aerobic exercise. However, no trial has assessed the efficacy of simultaneously implementing all of these recommendations. The objective of this study was to determine the effects on blood pressure and other cardiovascular disease risk factors of a comprehensive lifestyle intervention. We conducted a randomized controlled trial of 44 hypertensive, overweight adults on a single blood pressure medication. Participants were randomized to a lifestyle or control group. For 9 weeks, the lifestyle group was fed a hypocaloric version of the DASH diet that provided 100 mmol/d of sodium. This group also participated in a supervised, moderate-intensity exercise program 3 times per week. The control group received no intervention. Outcomes were ambulatory blood pressure, serum lipids, weight, and fitness. At the end of the intervention, mean weight loss in the lifestyle group, net of control, was 4.9 kilograms. In the lifestyle group mean net reductions in 24-hour ambulatory systolic and diastolic blood pressures were 9.5 mm Hg (P<0.001) and 5.3 mm Hg (P<0.002), respectively. Corresponding changes in daytime systolic and diastolic blood pressures were 12.1 mm Hg (P<0.001) and 6.6 mm Hg (P<0.001). The lifestyle group experienced mean reductions in total cholesterol (-25 mg/dL, P<0.001), low-density lipoprotein cholesterol (-18 mg/dL, P=0.005), high-density lipoprotein cholesterol (-5 mg/dL, P<0.001), net of control. In conclusion, among hypertensive overweight adults already on antihypertensive medication, a comprehensive lifestyle intervention can substantially lower blood pressure and improve blood pressure control.     

A meta-analysis of the effect of thiazolidinediones on blood pressure

In epidemiologic studies, insulin resistance is associated with hypertension. Thiazolidinediones (TZDs) are antidiabetic agents that decrease insulin resistance. Multiple clinical trials have evaluated the effect of TZDs on blood pressure (BP) with inconsistent results. The aim of this study was to estimate the effect of TZDs on BP. The authors searched PubMed for clinical trials published in English. A total of 37 clinical trials that reported a change in BP were included in the analysis. Trials with independent-group design and trials with pre-post design were evaluated separately. When compared with baseline, TZDs lowered systolic BP by 4.70 mm Hg (95% confidence interval, -6.13 to -3.27) and diastolic BP by 3.79 mm Hg (95% confidence interval, -5.82 to -1.77). When compared with placebo, TZDs lowered systolic BP by 3.47 mm Hg (95% confidence interval, -4.91 to -2.02) and diastolic BP by 1.84 mm Hg (95% confidence interval, -3.43 to -0.25). Thus, TZDs lower both systolic and diastolic BP, albeit the BP-lowering effect is small and may not be of clinical significance.     

Chronic dietary tyrosine supplements do not affect mild essential hypertension

The blood pressure and plasma norepinephrine response to oral tyrosine, the precursor of norepinephrine, supplementation (2.5 g t.i.d.) of regular meals was examined in 13 untreated patients with mild essential hypertension. Using a randomized double-blind crossover design, each 2-week treatment was followed by a 2-week supplement-free interval. Supine and standing blood pressure and plasma norepinephrine levels were measured at the beginning and end of each 2-week treatment. Plasma tyrosine levels increased (p less than 0.001) from 71.2 +/- 8.0 nM/ml at baseline to 152.8 +/- 17.4 nM/ml 2 hours after the tyrosine supplement. Blood pressure under control conditions was 144 +/- 3 Hg systolic, 91 +/- 2 mm Hg diastolic (109 +/- 2 mm Hg mean) after 30 minutes in the supine position and 148 +/- 4 mm Hg systolic, 102 +/- 3 mm Hg diastolic (117 +/- 3 mm Hg mean) after 5 minutes of standing. Plasma norepinephrine levels were 191 +/- 18 pg/ml in the supine subjects and 390 +/- 33 pg/ml in the standing subjects. No difference in systolic, diastolic, or mean blood pressure, heart rate, or plasma norepinephrine levels were seen between the beginning and end of each period or between groups. Individual changes in blood pressure showed no correlation with individual changes in norepinephrine levels. These results indicate that the addition of a tyrosine supplement to the usual diet of mild hypertensive subjects has no beneficial effect on blood pressure.     

Carryover effects after cessation of drug treatment: trophies or dreams?

BACKGROUND: In randomized trials of primary prevention, there has been interest in the persistence of a beneficial effect of therapy after treatment has been stopped. We investigated the impact of measurement error in the outcome on results of the trial of preventing hypertension (TROPHY), a trial of candesartan vs. placebo for preventing hypertension in prehypertensive subjects. METHODS: We simulated the TROPHY study design, assuming that candesartan reduced blood pressure by 8/6 mm Hg during treatment, but had no carryover effect after treatment stopped. We simulated individual true blood pressures in the TROPHY-eligible range of 130-140 mm Hg for systolic blood pressure and 80-90 mm Hg for diastolic blood pressure, and added individual measurement variability. As in TROPHY, incident hypertension was defined as any three occurrences of systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg. RESULTS: In the absence of any carryover effect, typical incidence curves for time to hypertension were similar to those from TROPHY. A significant difference in cumulative incidence 2 years after stopping treatment was detected in 80% simulated studies, giving a Type I error rate of 80%. CONCLUSIONS: The published data from TROPHY are consistent with a lack of carryover effect of candesartan.