Mean Ambulatory Blood Pressure Research Articles

The Effect of Valsartan versus Non-RAAS Treatment on Autoregulation of Cerebral Blood Flow

Background: Cerebral autoregulation (CA) is a protective mechanism which maintains the steadiness of the cerebral blood flow (CBF) through a broad range of systemic blood pressure (BP). Acute hypertension has been shown to reduce the cerebrovascular adaptation to BP variations. However, it is still unknown whether CA is impaired in chronic hypertension. This study evaluated whether a strict control of BP affects the CA in patients with chronic hypertension, and compared a valsartan-based regimen to a regimen not inhibiting the renin-angiotensin-aldosterone system (non-RAAS). Methods: Eighty untreated patients with isolated systolic hypertension were randomized to valsartan 320 mg or to a non-RAAS regimen during 6 months. The medication was upgraded to obtain BP <140/90 mm Hg. Continuous recordings of arterial BP and CBF velocity (transcranial Doppler) were performed during periods of 5 minutes, at rest, and at different levels of alveolar CO₂ pressure provided by respiratory maneuvers. The dominant frequency of CBF oscillations was determined for each patient. Dynamic CA was measured as the mean phase shift between BP and CBF by cross-spectral analysis in the medium frequency and in the dominant CBF frequency. Results: Mean ambulatory 24-hour BP fell from 144/87 to 127/79 mm Hg in the valsartan group and from 144/87 to 134/81 mm Hg in the non-RAAS group (p = 0.13). Both groups had a similar reduction in the central BP and in the carotido-femoral pulse wave velocity. The average phase shift between BP fluctuations and CBF response at rest was normal at randomization (1.82 ± 0.08 s), which is considered a preserved autoregulation and increased to 1.91 ± 0.12 s at the end of study (p = 0.45). The comparison of both treatments showed no significant difference (–0.01 ± 0.17 s vs. 0.16 ± 0.16 s, p = 0.45) for valsartan versus non-RAAS groups. The plasmatic level of glycosylated hemoglobin decreased in the valsartan arm compared to the non-RAAS arm (–0.23 ± 0.06 vs. –0.08 ± 0.07%, p = 0.07). Conclusions: In elderly hypertensive men with isolated chronic systolic hypertension, CA seems efficient at baseline and is not significantly affected by 6 months of BP-lowering treatment. This suggests that the preventive effects of BP medication against stroke are not mediated through a restoration of the CA.

Sustained decrease in blood pressure following missed doses of aliskiren or telmisartan

The AliSkiren Study of profound antihypERtensive efficacy in hyperTensIVE patients (ASSERTIVE) study was designed to assess the sustained blood pressure (BP)-lowering effect of aliskiren vs. telmisartan after a 7-day treatment withdrawal in patients with hypertension. Patients were randomized to once-daily aliskiren 150 mg (N = 414) or telmisartan 40 mg (N = 408). After 2 weeks, all patients were uptitrated to double the initial dose for 10 weeks; subsequently, all patients were treated with placebo to simulate a 7-day treatment withdrawal. At the end of active treatment (EoA), similar decreases in mean ambulatory BP were observed with aliskiren and telmisartan. From EoA to day 7 of treatment withdrawal (end of withdrawal, EoW), the least squares mean increase in 24-h mean ambulatory SBP was smaller for aliskiren (2.7 mmHg) vs. telmisartan (6.5 mmHg). Between-treatment difference was significant in favour of aliskiren (-3.8 mmHg; P < 0.0001). Similar effects were observed for the increase in 24-h mean ambulatory DBP after EoW (-2.1 mmHg; P < 0.0001). Mean sitting SBP and DBP were also significantly lower with aliskiren than telmisartan after EoW with SBP (2.0 mmHg) and DBP (1.1 mmHg) differences in favour of aliskiren, already evident on day 2 after a single 'missed dose'. Aliskiren showed a greater and more sustained BP-lowering effect than telmisartan during a 7-day treatment withdrawal. Aliskiren may provide sustained BP lowering during 1 day or more missed dose.

Comparative Efficacy of Aliskiren/Valsartan vs Valsartan in Nocturnal Dipper and Nondipper Hypertensive Patients: A Pooled Analysis

This pooled analysis of ambulatory blood pressure (BP) monitoring data from two 8-week randomized controlled trials compared the antihypertensive efficacy and safety of combination aliskiren/valsartan vs valsartan alone in hypertensive patients (nocturnal dippers or nondippers). At study end, patients were taking aliskiren/valsartan 300/320 mg or valsartan 320 mg. In dippers (n=138) and nondippers (n=132), aliskiren/valsartan provided significantly (P<.05) greater reductions from baseline to week 8 than valsartan in 24-hour, daytime, and last-4-hour mean ambulatory systolic BP (maSBP). Treatment differences were more pronounced in nondippers. Nighttime maSBP reductions with aliskiren/valsartan were significantly greater vs valsartan in nondippers (-17.0 mm Hg vs -8.9 mm Hg; P<.05) but not dippers (-7.6 mm Hg vs -4.5 mm Hg; P=.16). In all time periods, combination therapy was generally associated with BP reductions that were greater in nondippers than dippers. Conversion from nondipper to dipper status was 32% vs 22% for aliskiren/valsartan vs valsartan (P=.48). Both treatments were similarly well tolerated. Although the addition of aliskiren to valsartan did not significantly alter dipper status, our data suggest an increased contribution of the renin-angiotensin-aldosterone system to the nondipper status of hypertensive patients.

Olmesartan medoxomil combined with hydrochlorothiazide improves 24-hour blood pressure control in moderate-to-severe hypertension

Background:Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has been shown to be more reliable than conventional measurements for hypertension assessment and the associated increased risk of cardiovascular events. Olmesartan/hydrochlorothiazide combination therapy has demonstrated increased blood pressure lowering over 24 hours compared with the component monotherapies. This prespecified pooled analysis of data from two trials investigated the effects of olmesartan/hydrochlorothiazide combination therapy and olmesartan monotherapy on 24-hour blood pressure control in patients with moderate-to-severe hypertension.Methods:After 8 weeks’ open-label olmesartan 40 mg monotherapy, uncontrolled patients (mean trough seated blood pressure 90–115/140–180 mmHg and 24-hour mean ambulatory diastolic blood pressure ≥80 mmHg with ≥30% of daytime ambulatory diastolic blood pressure readings >85 mmHg) were randomised to 8 weeks’ double-blind treatment with olmesartan 40 mg or olmesartan/hydrochlorothiazide 20/12.5, 40/12.5 or 40/25 mg (Study 1) or olmesartan/hydrochlorothiazide 20/25 or 40/25 mg (Study 2). This prespecified analysis of ambulatory blood pressure was performed on patients from the full analysis set of pooled studies 1 and 2, restricted to patients who provided at least one valid ABPM measurement at baseline.Results:After 8 weeks’ double-blind treatment, reductions in 24-hour, daytime and night-time blood pressure from baseline were observed for all treatment groups. These reductions were dose-dependent, with olmesartan/hydrochlorothiazide 40/25 mg demonstrating the greatest reductions in 24-hour blood pressure from baseline to Week 16 versus olmesartan monotherapy: −14.0/−8.8 vs −2.7/−2.0 mmHg, respectively; p < 0.0001.Conclusions:Adding hydrochlorothiazide to olmesartan provides more effective 24-hour blood pressure control versus olmesartan monotherapy in patients with moderate-to-severe hypertension.Clinical trial registration:Trial registration: ClinicalTrials.gov identifier: NCT00430508.Trial registration: ClinicalTrials.gov identifier: NCT00430950.

Ambulatory and Home Blood Pressure Measurement

See related article, pp 22–28 Clinic (office) blood pressure (BP) measurement has a well-established role in medical practice and is the standard on which most of the literature is based. However, clinic BP has several important limitations, including the potential for inadequate or misleading estimates of a patient's true BP status and suboptimal prediction of cardiovascular risk. Particularly relevant is the concern that clinic BP measured with standard techniques may not provide a representative estimate of an individual's usual BP outside the medical setting. Out-of-office BP assessment takes 2 forms at the present time, self (or home) BP measurement (SBPM) and ambulatory BP monitoring (ABPM). These 2 techniques have attracted considerable attention in recent years because of the potential for better classification of hypertensive status compared with office BP. SBPM devices allow for repeated measurements outside the medical environment, and their use has been recommended by several international guidelines.1,2 ABPM is currently considered the gold standard for the correct diagnosis of hypertension on the grounds that the ambulatory BP provides extensive information on several BP parameters other than the average BP, including BP variability, the morning BP surge, BP load, and the nocturnal fall in BP.3 However, it should be noted that all of the clinical guidelines still focus on the importance of the mean ambulatory BP for clinical practice, and all of the other parameters are still considered experimental. ABPM is not widely available in primary care practice and is considered most helpful when self-measured BP is within borderline values. According to most authorities, self-BP measurement should be used as an initial step to evaluate the out-of-office BP1–3 and, thus, used as a screening procedure that should lead to an ABPM for confirmation. However, it is not well known whether this strategy …

Effects of 24-Hour Blood Pressure and Heart Rate Recorded With Ambulatory Blood Pressure Monitoring on Recovery From Acute Ischemic Stroke

This study used ambulatory blood pressure (BP) monitoring to generate BP and heart rate (HR) profiles soon after stroke onset and evaluated the association between determined values and 3-month stroke outcomes. We analyzed 24-hour ambulatory BP monitoring records from 104 patients with acute ischemic stroke. Ambulatory BP monitoring was attached at the second and eighth hospitalization days (Days 1 and 7). Both BP and HR were characterized using baseline, mean, maximum, and minimum values and coefficient of variation during 24-hour recording periods. Outcomes at 3 months were assessed as independence according to a modified Rankin Scale score of ≤2 and poor according to the score of ≥5. Sixty-six (63%) patients achieved independence and 12 (11%) had poor outcomes. Mean ambulatory BP monitoring values changed from 150.5±19.5/85.7±11.3 mm Hg on Day 1 to 139.6±19.3/80.0±11.7 mm Hg on Day 7. After multivariate adjustment, mean values of systolic BP (OR, 0.63; 95% CI, 0.45-0.85), diastolic BP (0.61; 0.37-0.98), pulse pressure (0.55; 0.33-0.85), and HR (0.61; 0.37-0.98) recorded on Day 1 as well as mean HR on Day 7 (0.47; 0.23-0.87) were inversely associated with independence and mean values of systolic BP (1.92; 1.15-3.68), diastolic BP (5.28; 1.92-22.85), and HR (4.07; 1.83-11.88) on Day 1 as well as mean HR on Day 7 (4.92; 1.36-36.99) were positively associated with a poor outcome. All of systolic BP, diastolic BP, pulse pressure, and HR on Day 1 and HR on Day 7 assessed using ambulatory BP monitoring were associated with outcomes of patients with stroke at 3 months.

Ambulatory blood pressure profile and left ventricular geometry in Nigerian hypertensives

Background:Left ventricular hypertrophy (LVH) is an independent cardiac risk factor in hypertensives and the structural classification of left ventricular (LV) geometry provides additional prognostic information. Ambulatory blood pressure (ABP) monitoring has been shown to be superior to office blood pressure (BP) in relation to hypertension LVH. We investigated ambulatory BP variables in relation to LV geometric patterns in Nigerian hypertensives.Materials and Methods:A total of 130 patients (males = 96, females = 34) with hypertension had their 24-hours ambulatory BP and trans-thoracic 2D/M- mode echocardiography. Data were analyzed with SPSS 13.0. P < 0.05 was considered statistically significant.Results:The mean age of the patients was 54.08±11.88 years. The prevalence rate of abnormal LV geometry was 48.4%. Mean ambulatory Systolic BP (day time, night time and 24-hour-average) was significantly higher in patients with LVH compared with those without LVH. Day-night systolic and diastolic BP decay (i.e. percentage nocturnal decline in BP) was also significantly lower in LVH group than in the group without LVH. Patients with eccentric LVH had abnormal day time mean ambulatory systolic BP, night time mean ambulatory systolic BP, elevated day time and night time systolic BP loads, as well as non-dipping diastolic BP pattern. Significant correlates of LV mass index in this study population were mean ambulatory systolic BP (day time: r = 0.355, P = 0.004; night time: r = 0.343, P = 0.005; 24- hour average: r = 0.358, P = 0.004) and day-night decay (systolic: r = -0.388, P = 0.007; diastolic: r = -0.290, P = 0.022) as well as 24-hour systolic BP variability.Conclusion:The presence of LVH in hypertension was associated with higher mean ambulatory systolic BP and lower percentage nocturnal decline in systolic and diastolic BP than its absence which appeared to be worse in patients with eccentric LV geometry when compared with other geometric patterns.

Comparison of the Novel Angiotensin II Receptor Blocker Azilsartan Medoxomil vs Valsartan by Ambulatory Blood Pressure Monitoring

Azilsartan medoxomil (AZL-M) is a unique angiotensin II receptor blocker (ARB) under development for the treatment of hypertension. To compare this ARB with another in the class, the authors studied the effects of AZL-M and valsartan (VAL) in 984 patients with primary hypertension in a randomized, double-blind, multicenter study using ambulatory and clinic blood pressure (BP) measurements. The primary end point was change from baseline in 24-hour mean ambulatory systolic BP following 24 weeks of treatment. Hierarchical analysis testing for noninferiority was followed by superiority testing of AZL-M (80 mg then 40 mg) vs VAL. The mean age of participants was 58 years, 52% were men, and 15% were black. Baseline 24-hour mean systolic BP was similar (approximately 145.6 mm Hg) in each group. AZL-M 40 mg and 80 mg lowered 24-hour mean systolic BP (-14.9 mm Hg and -15.3 mm Hg, respectively) more than VAL 320 mg (-11.3 mm Hg; P<.001 for 40-mg and 80-mg comparisons vs VAL). Clinic systolic BP reductions were consistent with the ambulatory results (-14.9 mm Hg for AZL-M 40 mg and -16.9 mm Hg for AZL-M 80 mg vs -11.6 mm Hg for VAL; P=.015 and P<.001, respectively). The reductions in 24-hour mean and clinic diastolic BPs were also greater with both doses of AZL-M than with VAL (P≤.001 for all comparisons). Small, reversible changes in serum creatinine occurred more often with AZL-M than with VAL; otherwise, safety and tolerability parameters were similar among the three groups. These data demonstrate that AZL-M across the effective dose range had superior efficacy to VAL at its maximal recommended dose without any meaningful increase in adverse events. These findings suggest that AZL-M could provide higher rates of hypertension control compared with other ARBs in the class.

Ghrelin and its promoter variant associated with cardiac hypertrophy

The roles of ghrelin, a peptide hormone that has a role in regulating food intake and energy homeostasis, in the cardiovascular system have not yet been unambiguously established. We evaluated the association between plasma ghrelin concentrations and -501A>C single-nucleotide polymorphism (SNP) in the ghrelin gene 5' flanking area and echocardiographic measurements in 1037 middle-aged subjects. Left ventricular mass index (LVMI) was calculated according to Devereux's method. The ambulatory blood pressure (BP) was recorded using the fully automatic SpaceLabs 90207 oscillometric unit. Results suggested that plasma ghrelin was not related to mean ambulatory BP values. However, the highest plasma ghrelin tertile was associated with increased intraventricular septum (P=0.043) and posterior ventricular wall (P=0.002) thicknesses as well as left ventricular mass (P=0.05). After adjustment for age, sex, body mass index and systolic BP, the association persisted between ghrelin tertiles and intraventricular septum (P=0.05) and posterior ventricular wall (P=0.001) thicknesses. The SNP -501A>C polymorphism was associated with LVMI after adjustments for age, sex and systolic BP. In conclusion, ghrelin and its promoter variant are associated with cardiac hypertrophy indexes independent of BP. Positive correlation between ghrelin levels and increased wall thickness parameters may reflect compensatory up-regulation of ghrelin concentrations or direct effects of ghrelin on myocardium. The effects of the SNP seem not to be mediated through its effects on ghrelin plasma levels.

Comparison of antihypertensive efficacy of carvedilol and nebivolol in mild-to-moderate primary hypertension: a randomized trial

The aim of the present study is to compare the antihypertensive effects of carvedilol and nebivolol in mild-to-moderate hypertensive patients. It is a prospective; placebo-controlled, cross-over, double-blind, randomized, single-center clinical trial. Patients (n=20) who were first diagnosed with mild to moderate systemic hypertension according to mean ambulatory blood pressure measurements > 130/85 mmHg and no previous antihypertensive therapy were prospectively enrolled into the study. After 10 days of placebo run-in period, they were randomized within the same group as cross-over design to one month carvedilol 25 mg and one month nebivolol 5 mg regimen given once daily in the morning. The primary outcome variables were systolic and diastolic blood pressures determined by 24-hour ambulatory blood pressure measurements. Mutlivariate analysis of variance for repeated measurements with 3x2 factorial design was used for statistical analysis of results. The study group consisted of 6 women and 14 men whose mean age was 42.9±12.8 years (range 19-63 years). Mean heart rate was significantly decreased after commencing both carvedilol (70.2±5.2 bpm) and nebivolol (64.9±3.9 bpm) treatments compared to placebo (78.8±5.2 bpm) (p<0.05). Both carvedilol (133.8±9/86.6±8.6 mmHg) and nebivolol (134±8.7/85.6±7.4 mmHg) significantly decreased mean systolic and diastolic blood pressures compared to placebo (143.9±8.9/94.4±9.2 mmHg), respectively (p<0.05). However, there was no significant difference in decreasing either systolic or diastolic blood pressure between nebivolol and carvedilol therapies (p>0.05). No side effects were recorded during both carvedilol and nebivolol treatments. Although both carvedilol and nebivolol effectively decreased blood pressure compared to placebo, they showed similar efficacy for lowering blood pressure.

Tolerability of the Oscar 2 ambulatory blood pressure monitor among research participants: a cross-sectional repeated measures study

BackgroundAmbulatory blood pressure monitoring (ABPM) is increasingly used to measure blood pressure (BP) in research studies. We examined ease of use, comfort, degree of disturbance, reported adverse effects, factors associated with poor tolerability, and association of poor tolerability with data acquisition of 24-hour ABPM using the Oscar 2 monitor in the research setting.MethodsSixty adults participating in a research study of people with a history of borderline clinic BP reported on their experience with ABPM on two occasions one week apart. Poor tolerability was operationalized as an overall score at or above the 75th percentile using responses to questions adapted from a previously developed questionnaire. In addition to descriptive statistics (means for responses to Likert-scaled "0 to 10" questions and proportions for Yes/No questions), we examined reproducibility of poor tolerability as well as associations with poor tolerability and whether poor tolerability was associated with removal of the monitor or inadequate number of BP measurements.ResultsThe mean ambulatory BP of participants by an initial ABPM session was 148/87 mm Hg. After wearing the monitor the first time, the degree to which the monitor was felt to be cumbersome ranged from a mean of 3.0 to 3.8, depending on whether at work, home, driving, or other times. The most bother was interference with normal sleeping pattern (mean 4.2). Wearers found the monitor straightforward to use (mean 7.5). Nearly 67% reported that the monitor woke them after falling asleep, and 8.6% removed it at some point during the night. Reported adverse effects included pain (32%), skin irritation (37%), and bruising (7%). Those categorized as having poor tolerability (kappa = 0.5 between sessions, p = 0.0003) were more likely to report being in fair/poor health (75% vs 22%, p = 0.01) and have elevated 24-hour BP average (systolic: 28% vs 17%, p = 0.56; diastolic: 30% vs 17%, p = 0.37). They were also more likely to remove the monitor and have inadequate numbers of measurements.ConclusionsThe Oscar 2 ABPM device is straightforward to use but can interfere with sleep. Commonly reported adverse effects include pain, skin irritation, and bruising. Those who tolerate the monitor poorly are more likely to report being in fair or poor health and to remove it, particularly at night.

24-Hour ambulatory blood pressure control with triple-therapy amlodipine, valsartan and hydrochlorothiazide in patients with moderate to severe hypertension

To determine the effectiveness and safety of once-daily combination therapy with amlodipine, valsartan and hydrochlorothiazide for reducing ambulatory blood pressure (ABP) in patients with moderate to severe hypertension, a multicenter, double-blind study was performed (N=2271) that included ABP monitoring in a 283-patient subset. After a single-blind, placebo run-in period, patients were randomized to receive amlodipine/valsartan/hydrochlorothiazide (10/320/25 mg), valsartan/hydrochlorothiazide (320/25 mg), amlodipine/valsartan (10/320 mg) or amlodipine/hydrochlorothiazide (10/25 mg) each morning for 8 weeks. Efficacy assessments included change from baseline in 24-h, daytime and night time mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Statistically significant and clinically relevant reductions from baseline in all these parameters occurred in all treatment groups (P<0.0001, all comparisons versus baseline). At week 8, least squares mean reductions from baseline in 24-h, daytime and night time mean ambulatory SBP/DBP were 30.3/19.7, 31.2/20.5 and 28.0/17.8 mm Hg, respectively, with amlodipine/valsartan/hydrochlorothiazide; corresponding reductions with dual therapies ranged from 18.8–24.1/11.7–15.5, 19.0–25.1/12.0–16.0 and 18.3–22.6/11.1–14.3 mm Hg (P⩽0.01, all comparisons of triple versus dual therapy). Treatment with amlodipine/valsartan/hydrochlorothiazide maintained full 24-h effectiveness, including during the morning hours; all hourly mean ambulatory SBP and mean ambulatory DBP measurements were ⩽130/85 mm Hg at end point. Amlodipine/valsartan/hydrochlorothiazide combination therapy was well tolerated. Once-daily treatment with amlodipine/valsartan/hydrochlorothiazide (10/320/25 mg) reduces ABP to a significantly greater extent than component-based dual therapy and maintains its effectiveness over the entire 24-h dosing period.

Peripheral and Central Blood Pressure Responses of Combination Aliskiren/Hydrochlorothiazide and Amlodipine Monotherapy in African American Patients With Stage 2 Hypertension: The ATLAAST Trial

Efficacy of antihypertensive agents on central blood pressure (BP) in African Americans is not well studied. The authors report on an 8-week double-blind, randomized study of African American patients with stage 2 hypertension that compared brachial and central BP responses (substudy of 53 patients) to combination aliskiren/hydrochlorthiazide (HCTZ) and amlodipine monotherapy. Following a 1- to 4-week washout, initial therapy was aliskiren/HCTZ 150/12.5 mg (n=166) or amlodipine 5 mg (n=166) for 1 week, forced-titrated to aliskiren/HCTZ 300/25 mg or amlodipine 10 mg for 7 weeks. Mean seated systolic BP reductions from baseline was similar with both treatments (-28.6 mm Hg with aliskiren/HCTZ vs -28.2 mm Hg with amlodipine). In the substudy, significantly greater reductions in central systolic BP was observed with aliskiren/HCTZ vs amlodipine (-30.1 mm Hg vs -21.2; P=.031), although 24-hour mean ambulatory BP reductions between the two groups were similar. Central pressure is considered an important risk factor in African Americans, and these findings may suggest a new treatment option for these patients.

Body mass index, leptin, and ambulatory blood pressure variability in healthy adults

ObjectiveTo investigate the association between body mass index (BMI) and 24-h ambulatory blood pressure (ABP) variability, and to assess whether leptin might act as a mediator of this association. MethodsA cross-sectional study in healthy, normotensive men and women (n=156). BMI was derived from direct height and weight measurements made on each participant. All participants underwent 24-h ABP monitoring, and two measures of ABP variability were derived – the weighted standard deviation (wSD) and the average real variability (ARV). Plasma leptin was measured using an enzyme lined immunosorbant assay. ResultsIn linear regression models adjusted for demographic factors, glucose, creatinine, lipids, and mean ABP, BMI showed positive and statistically significant associations with diastolic wSD, and systolic and diastolic ARV. For those in the low, intermediate, and high BMI groups, mean values for diastolic wSD were 7.7, 7.9, and 8.5mmHg, respectively (p=.02); mean values of systolic ARV were 8.2, 8.2, and 9.0mmHg, respectively (p=.02); and mean values of diastolic ARV were 6.7, 7.0, and 7.5mmHg, respectively (p=.01). Similarly, leptin showed positive and statistically significant associations with measures of wSD and ARV. When BMI was entered as an ordinal variable in regression models for wSD and ARV, adjustment for leptin attenuated significant ordinal BMI coefficients by as much as 60%, suggesting a mediating role for leptin. ConclusionIn healthy adults, BMI and leptin show positive associations with ABP variability, and leptin may play a mediating role in this association.

Pharmacist-Physician Comanagement of Hypertension and Reduction in 24-Hour Ambulatory Blood Pressures

Pharmacist-physician comanagement of hypertension has been shown to improve office blood pressures (BPs). We sought to describe the effect of such a model on 24-hour ambulatory BPs. We performed a prospective, cluster-randomized, controlled clinical trial, enrolling 179 patients with uncontrolled hypertension from 5 primary care clinics in Iowa City, Iowa. Patients were randomized by clinic to receive pharmacist-physician collaborative management of hypertension (intervention) or usual care (control) for a 9-month period. In the intervention group, pharmacists helped patients to identify barriers to BP control, counseled on lifestyle and dietary modifications, and adjusted antihypertensive therapy in collaboration with the patients' primary care providers. Patients were seen by pharmacists a minimum of every 2 months. Ambulatory BP was measured at baseline and at study end. Baseline and end-of-study ambulatory BP profiles were evaluated for 175 patients. Mean (SD) ambulatory systolic BPs (SBPs), reported in millimeters of mercury, were reduced more in the intervention group than in the control group: daytime change in (Δ) SBP, 15.2 (11.5) vs 5.5 (13.5) (P<.001); nighttime ΔSBP, 12.2 (14.8) vs 3.4 (13.3) (P<.001); and 24-hour ΔSBP, 14.1 (11.3) vs 5.5 (12.5) (P<.001). More patients in the intervention group than in the control group had their BP controlled at the end of the study (75.0% vs 50.7%) (P<.001), as defined by overall 24-hour ambulatory BP monitoring. Pharmacist-physician collaborative management of hypertension achieved consistent and significantly greater reduction in 24-hour BP and a high rate of BP control. Trial Registration clinicaltrials.gov Identifier: NCT00201045.

Increasing the doses of both diuretics and angiotensin receptor blockers is beneficial in subjects with uncontrolled systolic hypertension

Blood pressure (BP) control is frequently difficult to achieve in patients with predominantly elevated systolic BP. Consequently, these patients frequently require combination therapy including a thiazide diuretic such as hydrochlorothiazide (HCTZ) and an agent blocking the renin-angiotensin-aldosterone system. Current clinical practice usually limits the daily dose of HCTZ to 25 mg. This often leads to the necessity of using additional antihypertensive agents to control BP in a high proportion of patients. To compare the efficacy of two doses of losartan (LOS)⁄HCTZ combinations in patients with uncontrolled ambulatory systolic hypertension after six weeks of treatment with LOS 100 mg⁄HCTZ 25 mg (LOS100⁄HCTZ25). Following a two- to four-week washout period, subjects with a mean clinic sitting systolic BP of 160 mmHg or higher and a mean ambulatory daytime systolic BP (MDSBP) of 135 mmHg or higher on LOS100⁄HCTZ25 (n=105; 33 women and 72 men) were randomly assigned to receive LOS 150 mg⁄HCTZ 25 mg (group 1; n=53) or LOS 150 mg⁄HCTZ 37.5 mg (LOS150⁄HCTZ37.5, group 2; n=52). The primary end point was the difference in MDSBP reductions. At the end of the six-week treatment period, the respective additional decreases in MDSBP were 1.2 mmHg (P=0.335) on LOS 150 mg⁄HCTZ 25 mg and 5.6 mmHg (P<0.0001) on LOS150⁄HCTZ37.5 (difference of 4.4 mmHg; P=0.011). Daytime systolic ambulatory BP goal (lower than 130 mmHg) achievement tended to be higher (25% versus 17%; P=0.313) with LOS150⁄HCTZ37.5, while it was significantly higher (65% versus 43%; P=0.024) for mean daytime diastolic BP (lower than 80 mmHg). No deleterious metabolic changes were observed. In patients with uncontrolled systolic ambulatory hypertension receiving LOS100⁄HCTZ25, increasing both HCTZ and LOS dosages simultaneously to LOS150⁄HCTZ37.5 may be an effective strategy that does not affect metabolic parameters.

Effects of High- and Low-Sodium Diets on Ambulatory Blood Pressure in Patients With Hypertension Receiving Aliskiren

Dietary sodium reduction and, as necessary, pharmacologic treatment are recommended for hypertension management. This prospective, randomized, open-label, blinded-end point, multicenter, crossover study investigated the effect of dietary sodium intake on mean ambulatory systolic blood pressure (maSBP) in patients with hypertension receiving aliskiren 300 mg once daily. Following a 2- to 4-week washout period, patients were randomized to a high- (≥ 200 mmol/d) or low- (≤ 100 mmol/d) sodium diet and were started on aliskiren, 300 mg/d. After 4 weeks, patients were crossed over to the alternate diet for an additional 4 weeks. The primary efficacy variable was change in maSBP between diets. During treatment with aliskiren, maSBP was significantly lower with the low-sodium diet compared with the high-sodium diet (least squares mean difference, 9.4 mm Hg; 95% CI, 7.5-11.4; P < .0001). The percentage of patients achieving a maSBP response to aliskiren (<130 mm Hg or a ≥ 20-mm Hg reduction from baseline) was greater with the low- (76.5%) versus the high-sodium diet (42.6%; P < .0001). Overall, 40.9% patients had ≥ 1 adverse event and the rates were similar between groups. In this study, aliskiren was well tolerated and a low-sodium diet accentuated its antihypertensive effect.

24‐Hour Ambulatory Blood Pressure Response to Combination Valsartan/Hydrochlorothiazide and Amlodipine/Hydrochlorothiazide in Stage 2 Hypertension by Ethnicity: The EVALUATE Study

Several studies reported racial/ethnic differences in blood pressure (BP) response to antihypertensive monotherapy. In a 10-week study of stage 2 hypertension, 320/25 mg valsartan/hydrochlorothiazide (HCTZ) reduced ambulatory BP (ABP) significantly more effectively than 10/25 mg amlodipine/HCTZ. Results (post hoc analysis) are described in Caucasians (n=256), African Americans (n=79), and Hispanics (n=86). Compared with clinic-measured BP (no significant treatment-group differences in ethnic subgroups), least-squares mean reductions from baseline to week 10 in mean ambulatory systolic BP (MASBP) and mean ambulatory diastolic BP (MADBP) favored valsartan/HCTZ over amlodipine/HCTZ in Caucasians (-21.9/-12.7 mm Hg vs -17.6/-9.5 mm Hg; P=.0004/P<.0001). No treatment-group differences in MASBP/MADBP were observed in African Americans (-17.3/-10.6 vs -17.9/-9.5; P=.76/P=.40) or Hispanics (-17.9/-9.7 vs -14.2/-7.2; P=.20/P=.17). Based on ABP monitoring, valsartan/HCTZ is more effective than amlodipine/HCTZ in lowering ABP in Caucasians. In African Americans and Hispanics, both regimens are similarly effective.

Efficacy of an olmesartan medoxomil-based treatment algorithm in patients with hypertension and type 2 diabetes: analysis of diurnal blood pressure control as assessed by 24-hour ambulatory blood pressure monitoring

Secondary, prespecified analysis of a single-arm, open-label study evaluating the efficacy of olmesartan medoxomil (OM) plus hydrochlorothiazide (HCTZ) in patients with hypertension and type 2 diabetes. After placebo run-in, 192 patients received OM 20 mg/day for 3 weeks. If blood pressure (BP) remained ≥120/70 mmHg, patients were uptitrated every 3 weeks to OM 40 mg/day, OM/HCTZ 40/12.5 mg/day, and OM/HCTZ 40/25 mg/day. Efficacy was evaluated by 24-hour ambulatory BP monitoring. Secondary endpoints included changes in ambulatory systolic BP (SBP) and diastolic BP (DBP) during daytime (08:00 to 16:00) and nighttime (22:00 to 06:00), as well as achievement of prespecified ambulatory BP targets in the total cohort and subgroups based on gender, race, hypertension severity, and age (≥65 or <65 years). Dipper status (nocturnal decrease in BP ≥10% of mean daytime BP) was assessed. At baseline, mean ambulatory BP was 151.2 ± 12.7/87.6 ± 9.0 mmHg during the daytime and 140.3 ± 13.1/78.1 ± 8.6 mmHg during the nighttime. Mean daytime and nighttime ambulatory BP was reduced from baseline by 22.3 ± 13.7/12.0 ± 8.9 mmHg and 18.8 ± 12.4/ 10.2 ± 7.2 mmHg, respectively. The reduction in daytime ambulatory SBP was 24.4 ± 11.8 mmHg in Blacks, 21.7 ± 14.2 mmHg in non-Blacks, 23.6 ± 12.3 mmHg in females, 21.2 ± 14.8 mmHg in males, 23.4 ± 11.6 mmHg in patients aged ≥65 years, and 21.9 ± 14.4 mmHg in those aged <65 years. Ambulatory BP targets of <130/80, <125/75, and <120/80 mmHg were reached by 51.7%, 36.0%, and 32.6% of patients during the daytime and 69.8%, 60.5%, and 50.6% of patients during the nighttime. After 12 weeks of treatment, 36.4% of baseline nondippers converted to dippers. OM ± HCTZ effectively lowered ambulatory BP in patients with type 2 diabetes and hypertension, enabling them to achieve ambulatory BP targets during both the daytime and nighttime.

Effects of the renin inhibitor MK-8141 (ACT-077825) in patients with hypertension

The renin inhibitor MK-8141 (ACT-077825) demonstrates substantial immunoreactive active renin (ir-AR) increase (sevenfold) without a persistent plasma renin activity (PRA) decrease. The present study assessed the antihypertensive efficacy of MK-8141 in hypertensive patients. In this double-blind, placebo- and active comparator-controlled study, 195 patients with hypertension (trough sitting diastolic blood pressure ≥92 to <105 mm Hg, trough sitting systolic blood pressure <170 mm Hg, and 24-hour mean diastolic blood pressure [DBP] ≥80 mm Hg) were randomized to one of four treatments (stratified by race, black versus others): MK-8141 250 mg, MK-8141 500 mg, enalapril 20 mg, or placebo. Blood pressure was measured at trough and as 24-hour ambulatory blood pressure monitoring. The primary end point was change from baseline in 24-hour mean ambulatory DBP measured after 4 weeks. At week 4, the change from baseline in 24-hour mean (95% CI) ambulatory DBP compared with placebo was −1.6 mm Hg (−4.2, 1.1), −1.1 mm Hg (−3.9, 1.6), and −4.9 (−7.5, −2.2) for MK-8141 250 mg, MK-8141 500 mg, and enalapril 20 mg, respectively. Only mean ambulatory DBP-lowering with enalapril 20 mg was statistically significant. Enalapril, but not MK-8141, also significantly lowered 24-hour mean ambulatory systolic blood pressure (SBP) compared with placebo (−6.7 mm Hg [−10.5, −2.8]). Neither enalapril nor MK-8141 significantly lowered trough DBP and SBP compared with placebo. MK-8141 was generally well tolerated. In patients with hypertension, MK-8141 (ACT-077825) did not produce significant blood pressure–lowering efficacy despite a demonstrated effect of the drug on ir-AR, in the absence of durable PRA suppression.