Significant Reduction In Systolic Blood Pressure Research Articles

Nurse‐led management of uncontrolled hypertension in those with diabetes and high vascular risk

AbstractThe aim of this audit was to determine the effectiveness of a protocol driven, nurse‐led hypertension service for patients with diabetes at high risk.Data for this audit were collected prospectively on referred patients with established diabetes complications and suboptimal hypertension control. Antihypertensive agents were sequentially introduced and dose titrated according to protocol. Patients were discharged once the target systolic blood pressure (SBP) of <140mmHg was achieved or the intended sequence of drug therapy was complete.In all, 124 patients completed the full process. There were significant reductions in SBP (186±24 to 139±12mmHg, p<0.001) and diastolic blood pressure (85±13 to 67±11mmHg, p<0.001). A total of 61% achieved the target SBP of <140mmHg. There were expected increases in the number of antihypertensive agents and the number of agents used to maximum dose. Estimated coronary heart disease risk for the primary prevention group improved significantly despite non‐significant changes in lipid profiles.It was concluded that a systematic approach combining a pre‐set drug protocol itself and its timely implementation under adequate surveillance in a nurse‐led hypertension clinic led to effective outcomes. Copyright © 2007 John Wiley & Sons.

Effect of a Pharmacy Care Program on Medication Adherence and Persistence, Blood Pressure, and Low-Density Lipoprotein Cholesterol

Poor medication adherence diminishes the health benefits of pharmacotherapies. Elderly patients with coronary risk factors frequently require treatment with multiple medications, placing them at increased risk for nonadherence. To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C). A multiphase, prospective study with an observational phase and a randomized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications. The study was conducted from June 2004 to August 2006. After a 2-month run-in phase (measurement of baseline adherence, BP, and LDL-C), patients entered a 6-month intervention phase (standardized medication education, regular follow-up by pharmacists, and medications dispensed in time-specific packs). Following the intervention phase, patients were randomized to continued pharmacy care vs usual care for an additional 6 months. Primary end point of the observation phase was change in the proportion of pills taken vs baseline; secondary end points were the associated changes in BP and LDL-C. Primary end point of the randomization phase was the between-group comparison of medication persistence. A total of 200 elderly patients (77.1% men; mean [SD] age, 78 [8.3] years), taking a mean (SD) of 9 (3) chronic medications were enrolled. Coronary risk factors included drug-treated hypertension in 184 patients (91.5%) and drug-treated hyperlipidemia in 162 (80.6%). Mean (SD) baseline medication adherence was 61.2% (13.5%). After 6 months of intervention, medication adherence increased to 96.9% (5.2%; P<.001) and was associated with significant improvements in systolic BP (133.2 [14.9] to 129.9 [16.0] mm Hg; P = .02) and LDL-C (91.7 [26.1] to 86.8 [23.4] mg/dL; P = .001). Six months after randomization, the persistence of medication adherence decreased to 69.1% (16.4%) among those patients assigned to usual care, whereas it was sustained at 95.5% (7.7%) in pharmacy care (P<.001). This was associated with significant reductions in systolic BP in the pharmacy care group (-6.9 mm Hg; 95% CI, -10.7 to -3.1 mm Hg) vs the usual care group (-1.0 mm Hg; 95% CI, -5.9 to 3.9 mm Hg; P = .04), but no significant between-group differences in LDL-C levels or reductions. A pharmacy care program led to increases in medication adherence, medication persistence, and clinically meaningful reductions in BP, whereas discontinuation of the program was associated with decreased medication adherence and persistence. clinicaltrials.gov Identifier: NCT00393419

Treatment of allergic rhinitis can improve blood pressure control

Owing to high prevalence of arterial hypertension (AH) and allergic rhinitis (AR), these diseases frequently coexist. The study aimed to assess whether improvement of AR by conventional treatment can improve blood pressure (BP) control in this population. Sixty-eight subjects of both sexes aged 35-60 years with AR and AH were randomized into two groups to receive in addition to their antihypertensive medications: treatment group (n=34) Fluticasone nasal 50 microg/spray b.i.d. and Fenoxifenadine 180 mg tablets q.d., and control group (n=34) 0.9% NaCl nasal drops b.i.d. Office BP and AR severity (using the Relative Quality of Life Questionnaire (RQLQ)) and high-sensitive C-reactive protein (hs-CRP) were measured at study entry and after 8 weeks in both groups, without changing of antihypertensive medications. In Treatment group an improvement in RQLQ, significant reduction of systolic BP (SBP) (DSBP 7.4 +/- 4.3 mm Hg, P=0.006) and reduction of hs-CRP level (DCRP 2.05 +/- 1.08; P=0.028) were observed, whereas diastolic BP (DBP) remained unchanged (DDBP 0.9 +/- 1.7 mm Hg, P=0.7). There was a significant correlation between DRQLQ and DSBP (r=0.86; P=0.019) and between DCRP and DSBP (r=0.56; P=0.027). No statistically significant changes of RQLQ, BP and CRP were observed in the control group. In patients with coincidence of AH and AR, medications meant to improve AR attenuate low-grade systemic inflammation and can lower SBP, but not DBP.

Combined calcium, magnesium and potassium supplementation for the management of primary hypertension in adults

Previous research suggests that increasing dietary intakes of calcium, potassium or magnesium separately may reduce BP to a small degree over the short term. It is unclear whether increasing intakes of a combination of these minerals produces a larger reduction in BP. To evaluate the effects of combined mineral supplementation as a treatment for primary hypertension in adults. We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review. The search was unrestricted by language or publication status. Inclusion criteria were: 1) RCTs of a parallel or crossover design comparing oral supplements comprising a combination of potassium, and/or calcium, and/or magnesium with placebo, no treatment, or usual care; 2) treatment and follow-up >=8 weeks; 3) participants over 18 years old, with raised systolic blood pressure (SBP) >=140 mmHg or diastolic blood pressure (DBP) >=85 mmHg with no known primary cause; 4) SBP and DBP reported at end of follow-up. We excluded trials where participants were pregnant, or received antihypertensive medication which changed during the study. Two reviewers independently extracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted. We included three RCTs (n=277) with between 24 and 28 weeks follow-up. Three combinations of minerals were investigated: potassium & magnesium, calcium & magnesium, and calcium & potassium. One trial investigated combinations of calcium & magnesium and of calcium & potassium, and for each found a statistically non-significant increase in both SBP and DBP. All three trials investigated the combination of potassium & magnesium. None of the trials provided data on mortality or morbidity. The combination of potassium & magnesium compared to control resulted in statistically non-significant reductions in both SBP (mean difference = -4.6 mmHg, 95% CI: -9.9 to 0.7) and DBP (mean difference = -3.8 mmHg, 95% CI: -9.5 to 1.8), although the results were heterogeneous (I(2)=68% and 85% for SBP and DBP respectively).A sensitivity analysis using alternative reported values which accounted for missing data had very little effect on DBP but resulted in a larger, statistically significant reduction in SBP (mean difference = -5.8 mmHg, 95% CI: -10.5 to -1.0). The quality of the trials was not well reported. We found no robust evidence that supplements of any combination of potassium, magnesium or calcium reduce mortality, morbidity or BP in adults. More trials are needed to investigate whether the combination of potassium & magnesium is effective.

The effect of a worksite based walking programme on cardiovascular risk in previously sedentary civil servants [NCT00284479

BackgroundA significant proportion of Europeans do not meet the recommendations for 30 mins of physical activity 5 times per week. Whether lower frequency, moderate intensity exercise alters cardiovascular disease (CVD) risk has received little attention. This study examined the effects of 45 minutes self-paced walking, 2 d· wk-1 on aerobic fitness, blood pressure (BP), body composition, lipids and C-Reactive Protein (CRP) in previously sedentary civil servants.Methods37 subjects (24 women) aged 41.5 ± 9.3 years were randomly assigned to either two 45 minute walks per week (walking group) or no training (control group). Aerobic fitness, body composition, blood pressure (BP), CRP and lipoprotein variables were measured at baseline and following 8 weeks. Steps counts were measured at baseline and during weeks 4 and 8 of the intervention.ResultsCompared to the control group, the walking group showed a significant reduction in systolic BP and maintained body fat levels (P < 0.05). There were no changes other risk factors. Subjects took significantly more steps on the days when prescribed walking was performed (9303 ± 2665) compared to rest days (5803 ± 2749; P < 0.001).ConclusionThese findings suggest that walking twice per week for 45 minutes at ~ 62% HRmax, improves activity levels, reduces systolic BP and prevents an increase in body fat in previously sedentary adults. This walking prescription, however, failed to induce significant improvements in other markers of cardiovascular disease risk following eight weeks of training.

Calcium supplementation for the management of primary hypertension in adults

Metabolic studies suggest calcium may have a role in the regulation of blood pressure. Some epidemiological studies have reported that people with a higher intake of calcium tend to have lower blood pressure. Previous systematic reviews and meta-analyses have reached conflicting conclusions about whether oral calcium supplementation can reduce blood pressure. To evaluate the effects of oral calcium supplementation as a treatment for primary hypertension in adults. We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review. Inclusion criteria were: 1) RCTs comparing oral calcium supplementation with placebo, no treatment, or usual care; 2) treatment and follow-up >/=8 weeks; 3) participants over 18 years old, with raised systolic blood pressure (SBP) >/=140 mmHg or diastolic blood pressure (DBP) >/=85 mmHg; 4) SBP and DBP reported at end of follow-up. We excluded trials where: participants were pregnant; received antihypertensive medication which changed during the study; or calcium supplementation was combined with other interventions. Two reviewers independently abstracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted. We included 13 RCTs (n=485), with between eight and 15 weeks follow-up. The results of the individual trials were heterogeneous. Combining all trials, participants receiving calcium supplementation as compared to control had a statistically significant reduction in SBP (mean difference: -2.5 mmHg, 95% CI: -4.5 to -0.6, I(2 )= 42%), but not DBP (mean difference: -0.8 mmHg, 95% CI: -2.1 to 0.4, I(2) = 48%). Sub-group analyses indicated that heterogeneity between trials could not be explained by dose of calcium or baseline blood pressure. Heterogeneity was reduced when poor quality trials were excluded. The one trial reporting adequate concealment of allocation and the one trial reporting adequate blinding yielded results consistent with the primary meta-analysis. In view of the poor quality of included trials and the heterogeneity between trials, the evidence in favour of causal association between calcium supplementation and blood pressure reduction is weak and is probably due to bias. This is because poor quality studies generally tend to over-estimate the effects of treatment. Larger, longer duration and better quality double-blind placebo controlled trials are needed to assess the effect of calcium supplementation on blood pressure and cardiovascular outcomes.

Efeitos de um programa de exercício físico não-supervisionado e acompanhado a distância, via internet, sobre a pressão arterial e composição corporal em indivíduos normotensos e pré-hipertensos

To verify the effects of a six-month non-supervised physical training program followed via the Internet on blood pressure and body composition in normotensive and borderline hypertensive individuals. One hundred and thirty five individuals were divided into two groups: 1) normotensive individual (n = 57), 43 +/- 1 years of age, systolic blood pressure (SBP) < 120 and diastolic blood pressure (DBP) < 80 mmHg (GI); and 2) borderline hypertensive individual (n = 78), 46 +/- 1 years of age, SBP 120 to 139 and DBP 80 to 89 mmHg (GII). After a three and six-month physical training, GII individuals showed a significant reduction in SBP (-3.6 +/- 0.94 and -10 +/- 0.94 mmHg, p < 0.05, respectively) and PAD (-6.5 +/- 1 and -7.1 +/- 0.9 mmHg, p < 0.05, respectively), body weight (-1.12 +/- 0.26 and -1.25 +/- 0.31 kg, p < 0.05, respectively), BMI (-0.79 +/- 0.4 and -0.84 +/- 0.41 kg/m2, p < 0.05, respectively) and waist circumference (-1.12 +/- 0.53 and -1.84 +/- 0.56 cm, p < 0.05, respectively). In the GI group, the physical training led to a decrease in waist circumference at the sixth month (-1.6 +/- 0.63 cm, p < 0.05). This program decreases blood pressure, body weight, BMI, and waist circumference in borderline hypertensive individuals, and is therefore a safe and low-cost strategy in the prevention of cardiovascular diseases and improvement of health status of the population.

Effect of progressive muscle relaxation in adolescent female bronchial asthma patients: A randomized, double-blind, controlled study

Objective The aim of this study is to examine the efficacy of progressive muscle relaxation (PMR) on change in blood pressure, lung parameters and heart rate in female adolescent asthmatics. Method In a prospective, randomized, double-blind, controlled study, adolescent female asthmatics ( n=31) were tested to find out how the systolic blood pressure (SBP), forced expiratory volume in the first second (FEV 1), peak expiratory flow (PEF) and heart rate change after PMR. The control group (CG; n=30) received a placebo intervention. Results A significant reduction in SBP and a significant increase in the FEV 1 and PEF were observed after PMR. The heart rate showed a significant increase in the coefficient of variation (CV), root-mean-square of successive differences (RMSSD) and at the high frequency (HF) range, in addition to a significant reduction at the low and middle frequency (LF and MF, respectively) ranges. Conclusion PMR appears to be effective in improvement of blood pressure, lung parameter and heart rate in adolescent female asthmatics.

Reduction in Framingham cardiovascular risk with concomitant treatment of hypertension/dyslipidemia with amlodipine/atorvastatin

Although recent consensus guidelines have stressed the importance of simultaneous management of multiple cardiovascular risk factors, the actual effects of such strategies have not been adequately tested. The Respond study assessed the efficacy of concurrent treatment of concomitant hypertension/dyslipidemia. Respond is a double-blind, double-dummy, placebo-controlled trial undertaken in 15 countries, which randomized 1,660 patients with hypertension and dyslipidemia to 1 of 15 combinations of amlodipine (placebo, 5, or 10 mg) and atorvastatin (placebo, 10, 20, 40, 80 mg). The main efficacy assessment was the mean change from baseline to end point in systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C). A key secondary analysis was change from baseline to end point in Framingham risk score in patients without coronary heart disease (CHD) or a risk equivalent (n = 861). At 8 weeks, combination-treated patients experienced dose-related and statistically significant reductions in SBP, LDL-C, and Framingham risk score, resulting in 7.7–11.2 mean percentage point reductions at end point (from mean baseline levels of 15.8–18.5%) in the estimated 10-year risk of developing CHD (Table). Mean reduction in estimated 10-year Framingham CHD risk score (percentage points) Mean reduction in estimated 10-year Framingham CHD risk score (percentage points) Simultaneous treatment of concomitant hypertension/dyslipidemia with amlodipine/atorvastatin is a highly effective strategy for reducing Framingham risk score.

Role of a selective aldosterone blocker in mice with chronic heart failure

Background Spironolactone, a nonselective aldosterone blocker, has a cardioprotective effect; however, significant endocrine side effects limit its use. Eplerenone is a new selective aldosterone blocker. We investigated whether eplerenone attenuates cardiac remodeling and improves function in a mouse model of heart failure and whether coadministration of eplerenone and an angiotensin-converting enzyme inhibitor (ACEi) provides better cardioprotection than either agent alone. Methods and results C57BL/6J mice were subjected to myocardial infarction (MI) by ligating the left anterior descending coronary artery. Two weeks later, the mice were either left untreated or treated with (1) eplerenone, (2) ACEi, or (3) eplerenone plus ACEi for 12 weeks. Systolic blood pressure (SBP) was measured and echocardiography performed before MI and weekly thereafter. At the end of the study, interstitial collagen fraction (ICF) and myocyte cross-sectional area (MCSA) were examined histologically. We found that (1) eplerenone significantly improved ejection fraction and cardiac output and decreased left ventricular (LV) systolic area, LV weight, ICF, and MCSA independently of changes in SBP compared with untreated animals; (2) ACEi had similar beneficial effects, accompanied by a significant reduction in SBP; and (3) combined treatment offered limited additional benefit beyond monotherapy. Conclusions In mice with MI, eplerenone attenuates progression of heart failure comparably to ACEi, and its effect is independent of BP lowering.

2-hydroxyoleic acid: a new hypotensive molecule.

Recent studies have shown that diets rich in monounsaturated fatty acids (MUFAs) from olive oil, a natural source of oleic acid, have beneficial effects on blood pressure (BP) in hypertensive patients. With this in mind, we investigated whether a synthetic derivative of the MUFA oleic acid, 2-hydroxyoleic acid (2-OHOA), was capable of regulating the BP of Sprague-Dawley rats. Intraperitoneal and oral administration of 2-OHOA to rats induced significant and sustained decreases in BP in a time-dependent manner. Without affecting heart rate, treatments for 7 days provoked reductions in systolic BP of 20 to 26 mm Hg. At the molecular level, the density of Galpha(s), but not Galpha(i2) or Galpha(o), increased in membranes from the hearts and aortas of 2-OHOA-treated rats, whereas in heart membranes, the density of Galpha(q)/11 and protein kinase Calpha proteins was also augmented. These molecular alterations were reflected in the increase in cAMP levels after Galpha(s) protein and beta-adrenergic receptor stimulation. On the contrary, inhibitory hormones reduced adenylyl cyclase activity to the same extent in 2-OHOA-treated rats as in vehicle-treated ones. Our results indicate that cardiovascular tissues from 2-OHOA-treated rats exhibited increased cAMP production in response to Galpha(s) activation, which might be attributed to enhanced expression of Galpha(s) proteins. As a result of this change, a significant reduction in systolic BP was observed. Therefore, BP can be lowered by administration of 2-OHOA, which might represent the first member of a new family of antihypertensive drugs.

Pharmacist intervention program for control of hypertension.

Pharmaceutical care programs have been shown to improve outcomes in hypertension. However, most programs required direct access to patient medical chart and patient consultation sessions by appointment. To follow the current practice of community pharmacy, exploring the effect of an intervention program on blood pressure (BP) and factors affecting BP. Treated hypertensive patients were enrolled in a 9-month controlled study involving 9 community pharmacies. The PRECEDE-PROCEED model was used as conceptual framework to identify factors affecting BP, to incorporate those factors in an intervention program, and to evaluate the impact of the program. A computerized decision-aid tool was used by pharmacists from 4 pharmacies to provide pharmaceutical care to subjects (n = 41); pharmacists from the 5 other pharmacies performed usual care (n = 59). As there was a statistically significant interaction due to family income in describing the impact of pharmacists' intervention on BP, population was stratified by family income in the analyses. Compared with the control group, the pharmacy program resulted in significant systolic BP reduction (-7.8 vs. 0.5 mm Hg; p = 0.01) and an increase in the proportion of controlled patients only for those with high incomes. In the high-income group, the program also had a positive impact on physical activity, self-reported adherence, health concerns, and information transmitted. The low-income group did not appear to benefit from the program. Pharmacist intervention can modify factors affecting adherence, improve adherence, and reduce BP levels in patients treated with antihypertensive agents. Impact of pharmacist intervention on BP differed according to patient income status.

Recurrent orthostatic numbness with carotid stenosis and beta-blocker use

patient had a left carotid endarterectomy and remains symptom free. Unlike many of the previously reported cases, our patient illustrates that a significant reduction in systolic BP (20 mm Hg) may not be necessary to cause ischemic symptoms. A minor drop (9 mm Hg systolic in our case) may symptomatically compromise blood flow across a stenosed artery if adequate collaterals are unavailable to a particular area of the brain. Anti-hypertensive medications can uncover otherwise asymptomatic carotid disease and alter the course of patient management by precipitating surgical intervention. Conversely, one could argue that these medications should be used cautiously in patients with known high-grade stenosis even in the absence of significant orthostatic hypotension. The TIA reported here is a classical example of a perfusion failure TIA. 5 These TIAs are frequently associated with severe carotid stenosis and signify distal insufficiency. The presentation is stereotypic, as illustrated by our patient, although the exact symptoms probably depend on the individual pattern of collateral supply.

Efficacy and safety of a once daily graded-release diltiazem formulation in essential hypertension

BackgroundThe efficacy and safety of a chronotherapeutic, graded-release diltiazem HCl extended-release (GRD) 120-, 240-, 360- and 540-mg dose administered once-daily at bedtime (10 pm) were evaluated in a 7-week randomized, double-blind comparison to placebo and to GRD 360 mg administered once-daily at 8 am in 478 patients with moderate-to-severe essential hypertension. MethodsWe assessed the change from baseline to end point in trough diastolic blood pressure (DBP) at 6 pm to 10 pm and in mean DBP from 6 am to 12 noon between GRD 360 mg pm and GRD 360 mg am, measured by ambulatory BP monitoring (ABPM). ResultsBedtime doses of GRD showed dose-related mean reductions in trough DBP that were significant for GRD doses of 240 mg and higher. Bedtime GRD 360 mg was associated with a significantly greater reduction in mean DBP between 6 am and 12 noon compared to morning GRD 360 mg with a least squares mean for treatment difference of −3.3 mm Hg (P = .0004). Similar dose-related and significant reductions in systolic BP (SBP) and heart rate (HR) were obtained. Incidence of adverse events (AEs) for all GRD groups (44.5%) was less than that obtained for the placebo group (49.3%). The 540-mg group showed an incidence of AEs (43.5%) similar to that observed for the 240-mg group (42.6%). ConclusionsThe GRD dose-dependently significantly reduces BP and HR over the 24-h interval after once-daily bedtime dosing. Further greater reductions were obtained between 6 am and 12 noon, when circadian BP is highest, compared to morning administration of the same dose. The 540-mg GRD was safe, well tolerated, and offers further therapeutic option for patients with severe hypertension who required additional BP control.

Effects of the calcium channel antagonist amlodipine in cats with surgically induced hypertensive renal insufficiency.

To determine whether amlodipine besylate decreases systemic arterial blood pressure (BP) and reduces the prevalence of complications in cats with induced hypertensive renal insufficiency. 20 cats with partial nephrectomy. Following reduction in renal mass, 10 cats were administered 0.25 mg of amlodipine/kg, PO, q 24 h (group A). Ten cats served as a control group (group C). Systolic BP (SBP), diastolic BP (DBP), and mean BP (MBP), physical activity, and pulse rate were measured continuously for 36 days by use of radiotelemetric devices. Compared with values for clinically normal cats, SBP, DBP, and MBP were significantly increased in cats of group C. Cats in group A had significant reductions in SBP, DBP, and MBP, compared with values for cats in group C. Albuminuria but not urine protein-to-creatinine ratio was significantly correlated (R2 = 0.317) with SBP in hypertensive cats. Prevalence of ocular lesions attributable to systemic hypertension in group C (7 cats) was greater than that observed in group A (2). Two cats in group C were euthanatized on day 16 because of nuerologic complications attributed to systemic hypertension. One normotensive cat in group A was euthanatized because of purulent enteritis of unknown cause on day 27. Amlodipine had an antihypertensive effect in cats with coexistent systemic hypertension and renal insufficiency. Its use may improve the prognosis for cats with systemic hypertension by decreasing the risk of ocular injury or neurologic complications induced by high BP.

Candesartan cilexetil: an update of its use in essential hypertension.

Candesartan cilexetil is converted to the angiotensin II receptor antagonist candesartan during absorption from the gastrointestinal tract. The selective and competitive binding of candesartan to the angiotensin II type 1 (AT(1)) receptor prevents binding of angiotensin II, a key mediator in the renin-angiotensin system. Significant reductions in systolic BP and diastolic BP are achieved with a once-daily dosage of candesartan cilexetil 2 to 32 mg/day in patients with mild to moderate hypertension. In randomised studies, candesartan cilexetil 8 to 16 mg/day was at least as effective as therapeutic dosages of losartan or other angiotensin II receptor antagonists. At a dosage of up to 32 mg/day candesartan cilexetil demonstrated greater antihypertensive efficacy than losartan 50 or 100 mg/day. In comparative trials, candesartan cilexetil demonstrated similar or greater antihypertensive efficacy compared with enalapril or hydrochlorothiazide and equivalent efficacy compared with amlodipine. The efficacy of candesartan cilexetil is not affected by age, and the drug provided significant BP reductions in Black patients and in those with severe hypertension. Long-term clinical studies to assess the effects of treatment with candesartan cilexetil on cardiovascular morbidity and mortality are ongoing. Regression of left ventricular hypertrophy has been seen with candesartan cilexetil treatment in patients with hypertension. Furthermore, the drug has favourable effects on renal function in patients with hypertension with or without coexisting diabetes mellitus. Renal vascular resistance and albumin excretion were reduced following treatment with candesartan cilexetil. Glucose homeostasis and lipid metabolism were not affected by treatment in patients with type 2 diabetes mellitus. Candesartan cilexetil is well tolerated and is not associated with cough, a common adverse effect of angiotensin converting enzyme inhibitor treatment. A pooled analysis of clinical trials found that the tolerability profile of candesartan cilexetil is not significantly different from that of placebo. Adverse events are not dose-related and are generally of mild to moderate severity. Candesartan cilexetil is an effective antihypertensive agent with a tolerability profile similar to that of placebo. Comparative data indicate that candesartan cilexetil has antihypertensive efficacy equivalent to that of other major classes of antihypertensive agents and has a long duration of action. Therefore, candesartan cilexetil is a useful therapeutic option in the management of patients with hypertension.

Differential effect of chronic inhibition of calcium channel and angiotensin II type 1-receptor on aldosterone synthesis in spontaneously hypertensive rats

We have investigated the in vivo effect of chronic blockade of Ca 2+-channels and angiotensin II type 1 (AT 1)-receptors on aldosterone (Aldo)-synthesis in the adrenal glands of spontaneously hypertensive rats (SHR). Male SHR were administered Ca 2+-antagonist, amlodipine (10 mg/kg per day) or AT 1-receptor-antagonist, TCV-116 (1 mg/kg per day) from 7 until 11 weeks of age. Systolic blood pressure (SBP) and heart rate (HR) were significantly higher in SHR than Wistar-Kyoto (WKY) rats. Both treatments resulted in equivalent and significant reduction in SBP in SHR. Aldo-secretion in SHR, which was significantly higher than in WKY rats, was profoundly suppressed by TCV-116 compared with amlodipine. Both treatments resulted in thickening of the zona glomerulosa, which immunohistochemically contains Aldo, at the end of therapy. Competitive reverse transcription-polymerase chain reaction (RT-PCR) showed that CYP11A (P450scc) mRNA regulating the first step of Aldo-synthesis was significantly reduced from week 9 of age by amlodipine, and that CYP11B2 (P450aldo) mRNA regulating the last step of Aldo-synthesis was potently suppressed from 9 weeks of age by TCV-116. Our results indicate that chronic treatment with different antihypertensive agents directly modulates adrenocortical aldosterone synthesis in SHR in vivo via different mechanisms.

Improvement in fatty acid utilization in relation to a change in left ventricular hypertrophy in spontaneously hypertensive rats.

Although fatty acid metabolism is reportedly impaired in myocardial hypertrophy, it is unclear whether the antihypertensive drugs are associated with improved fatty acid metabolism. In order to evaluate the effects of antihypertensive drugs on fatty acid metabolism and myocardial perfusion, the simultaneous uptake of iodine-125(125I)-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and thallium-201 (Tl) were measured in 3 groups of rats: (1) spontaneously hypertensive rats (SHR) without treatment (SHR-N), (2) SHR chronically treated with captopril (SHR-C), and (3) SHR chronically treated with hydralazine (SHR-H). Captopril and hydralazine were administered to their respective groups for 3 weeks from 12 weeks of age. The hearts were removed 10 min after simultaneous intravenous injections of BMIPP and Tl and the 125I and 201Tl counts were measured to calculate the uptake ratio. The systolic blood pressure (SBP) in SHR-N was 222+/-10 mm Hg, whereas the SHR-C and SHR-H groups showed significant SBP reduction (156+/-11, and 158+/-10 mm Hg, respectively) (p<0.01 each). The heart/bodyweight ratio was significantly lower in SHR-C (2.48+/-0.09) than in SHR-N (2.74+/-0.11) (p<0.05). However, there was no significant difference in the heart/bodyweight ratio between SHR-N and SHR-H (2.65+/-0.09). The ratio of BMIPP uptake to Tl uptake (BMIPP/Tl) was significantly higher in SHR-C (0.71+/-0.13) than in SHR-N (0.50+/-0.09) (p<0.05). However, BMIPP/Tl in SHR-H (0.53+/-0.09) was similar to that in SHR-N. These results suggest that captopril improves fatty acid metabolism in the hypertrophied ventricle in SHR. The metabolic alterations may improve with left ventricular hypertrophy regression but are not effected by the reduction of blood pressure only.

Efficacy of fosinopril in the control of 24-hour blood pressure in hemodialysis patients using ambulatory blood pressure monitoring

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was used to assess the efficacy and tolerability of fosinopril, an angiotensin-converting enzyme inhibitor, in 20 hemodialysis patients (12 men, 8 women; aged 28 to 64 years [mean, 54 ± 9 years]) with mild-to-moderate hypertension. After a 4-week washout period, during which the lowest possible dry weight was achieved, patients were given fosinopril 10 mg/d orally if their preanalysis blood pressure (BP) was ≥140/90 mm Hg. If BP was not controlled, the dosage was increased every 2 weeks as needed to a maximum of 40 mg/d. Fosinopril was administered for a total duration of 12 weeks. ABPM was done at the beginning of the study and repeated after 6 and 12 weeks of treatment. Significant changes in mean 24-hour systolic and diastolic BP were seen from baseline to week 12 (from 150.3 ± 4.8 to 138.2 ± 3.1 mm Hg and from 95.0 ± 2.8 to 84.3 ± 3.1 mm Hg, respectively) ( P < 0.0001). Significant reductions in mean 24-hour systolic and diastolic BP between baseline and week 6 were noted (from 150.3 ± 4.8 to 136.1 ± 4.8 mm Hg and from 95.0 ± 2.8 to 82.6 ± 2.5 mm Hg, respectively). The smoothness of BP control was demonstrated by a trough:peak ratio of 58% for ambulatory systolic BP and 62% for diastolic BP. In addition, at 12 weeks, fosinopril induced a significant reduction in systolic BP load from 66.6 ± 20.0% to 39.2 ± 16.5% and diastolic BP load from 67.1 ± 22.8% to 31.4 ± 6.6% ( P < 0.001). Blunting of the circadian rhythm was noted in all patients at study entry. No significant adverse effects were observed. Findings from the present study suggest that fosinopril, given in the usual doses, is well tolerated and results in smooth BP control in hemodialysis patients with mild-tomoderate hypertension

Enhanced blood pressure response to mild sodium reduction in subjects with the 235T variant of the angiotensinogen gene

The relationship of high salt intake to elevated blood pressure levels has been demonstrated in most populations by cross-sectional, longitudinal, physiological, and clinical intervention studies. Variation within the angiotensinogen gene has been implicated in the genetic control of blood pressure levels and has been suggested to contribute to increased salt sensitivity. A total of 86 hypertensive men and women who had never been treated and who had participated in a 6-month randomized, placebo-controlled, clinical trial of low-sodium mineral salt (19% reduction in urinary sodium versus 12% increase in placebo group) were genotyped at the angiotensinogen M235T locus to test the hypothesis that the 235T allele is associated with a significant blood pressure response to a sodium reduction intervention whereas the 235M allele is not. After adjustment for gender and baseline blood pressure, persons with the TT and MT genotypes showed significant systolic blood pressure reductions on mineral salt compared with control subjects ( P = .02 and P = .001, respectively) but not persons with the MM genotype ( P = .10). Net adjusted diastolic blood pressure reductions also showed greater significance for persons with the TT and MT genotypes than for persons with the MM genotype ( P = .08, P = .01, and P = .83, respectively). The net adjusted systolic and diastolic blood pressure reduction was −8.6/ −3.9 mm Hg for persons with the TT genotype, −9.0/ −5.2 mm Hg for the MT genotype, and −5.3/ −1.0 mm Hg for the MM genotype. We conclude that the 235T allele of the angiotensinogen gene is associated with greater blood pressure decreases than the 235M allele after a sodium reduction intervention. The angiotensinogen gene accounts for some of the interindividual variation of the blood pressure response to sodium reduction.