Toward a Definition of Masked Hypertension and White-Coat Hypertension among Hemodialysis Patients

Summary

Background and objectives

Among people with essential hypertension, ambulatory BP measurement is superior to BP obtained in the clinic in predicting cardiovascular outcomes. In part, this is because it can detect white-coat hypertension and masked hypertension. Whether the same is true for hemodialysis patients is not known.

Design, setting, participants, & measurements

Using a threshold of 140/80 mmHg for median midweek dialysis-unit BP and 135/85 mmHg for 44-hour ambulatory BP, we defined four categories of BP: sustained normotension (SN), white-coat hypertension (WCH), masked hypertension (MHTN), and sustained hypertension (SHTN).

Results

Among 355 long-term hemodialysis patients, the prevalence of SN was 35%, WCH 15%, MHTN 15%, and SHTN 35%. Over a mean follow-up of 29.6 (SD 21.7) months, 102 patients died (29%), yielding a crude mortality rate of 121/1000 patient-years. Unadjusted and multivariate-adjusted analyses showed increasing all-cause mortality with increasing severity of hypertension (unadjusted hazard ratios from SN, WCH, MHTN, SHTN: 1, 1.12, 1.70, 1.80, respectively [P for trend < 0.01]; adjusted hazard ratios: 1, 1.30, 1.36, 1.87, respectively [P for trend 0.02]). When a predialysis BP threshold of 140/90 mmHg was used to classify patients into BP categories, the prevalence of SN was 24%, WCH 26%, MHTN 4%, and SHTN 47%. Hazard ratios for mortality were similar when compared with median midweek dialysis-unit BP.

Conclusions

As in the essential hypertension population, MHTN and WCH have prognostic significance. The prognostic value of BP obtained in the dialysis unit can be refined with ambulatory BP monitoring.     

Intradialytic Hypertension and the Association with Interdialytic Ambulatory Blood Pressure

Summary

Background and objectives

Increasing BP during maintenance hemodialysis or intradialytic hypertension is associated with increased morbidity and mortality. In hemodialysis patients, ambulatory BP measurements predict adverse cardiovascular outcomes better than in-center measurements. We hypothesized that patients with intradialytic hypertension have higher interdialytic ambulatory systolic BP than those without intradialytic hypertension.

Design, setting, participants, & measurements

We performed a case-control study in adult hemodialysis patients. Cases consisted of subjects with intradialytic-hypertension (systolic BP increase ≥10 mmHg from pre- to posthemodialysis in at least four of six treatments), and controls were subjects with ≥10 mmHg decreases from pre- to posthemodialysis in at least four of six treatments. The primary outcome was mean interdialytic 44-hour systolic ambulatory BP.

Results

Fifty subjects with a mean age of 54.5 years were enrolled (25 per group) among whom 80% were men, 86% diabetic, 62% Hispanic, and 38% African American. The mean prehemodialysis systolic BP for the intradialytic-hypertension and control groups were 144.0 and 155.5 mmHg, respectively. Mean posthemodialysis systolic BP was 159.0 and 128.1 mmHg, for the intradialytic-hypertension and control groups, respectively. The mean systolic ambulatory BP was 155.4 and 142.4 mmHg for the intradialytic-hypertension and control groups, respectively (P = 0.005). Both daytime and nocturnal systolic BP were higher among those with intradialytic hypertension as compared with controls. There was no difference in interdialytic weight gain between groups.

Conclusions

Time-integrated BP burden as measured by 44-hour ambulatory BP is higher in hemodialysis patients with intradialytic hypertension than those without intradialytic hypertension.     

Empowering family physicians to impart proper inhaler teaching to patients with chronic obstructive pulmonary disease and asthma

BACKGROUND:

Patients with chronic obstructive pulmonary disease (COPD) and asthma depend on inhalers for management, but critical errors committed during inhaler use can limit drug effectiveness. Outpatient education in inhaler technique remains inconsistent due to limited resources and inadequate provider knowledge.

OBJECTIVE:

To determine whether a simple, two-session inhaler education program can improve physician attitudes toward inhaler teaching in primary care practice.

METHODS:

An inhaler education program with small-group hands-on device training was instituted for family physicians (FP) in British Columbia and Alberta. Sessions were spaced one to three months apart. All critical errors were corrected in the first session. Questionnaires surveying current inhaler teaching practices and attitudes toward inhaler teaching were distributed to physicians before and after the program.

RESULTS:

Forty-one (60%) of a total 68 participating FPs completed both before and after program questionnaires. Before the program, only 20 (49%) reported providing some form of inhaler teaching in their practices, and only four (10%) felt fully competent to teach patients inhaler technique. After the program, 40 (98%) rated their inhaler teaching as good to excellent. Thirty-four (83%) reported providing inhaler teaching in their practices, either by themselves or by an allied health care professional they had personally trained. All stated they could teach inhaler technique within 5 min. Observation of FPs during the second session by certified respiratory educators found that none made critical errors and all had excellent technique.

CONCLUSION:

A physician inhaler education program can improve attitudes toward inhaler teaching and facilitate implementation in clinical practices.     

Time response of alcohol-induced alterations in blood pressure, nitric oxide and oxidant to antioxidant balance in the plasma of rats

BACKGROUND:

Low to moderate alcohol consumption is known to reduce the risk of cardiovascular diseases; however, chronic high-dose alcohol ingestion causes cardiovascular injuries such as hypertension. The time response of alcohol-induced hypertension and associated tissue oxidative stress response has not been fully explored.

OBJECTIVES:

To investigate the time response of high-dose alcohol ingestion on blood pressure (BP) and to correlate the alterations in plasma nitric oxide (NO) levels and oxidative stress parameters in rats.

METHODS:

Male Fisher rats (200 g to 250 g) were divided into two groups of 30 animals each and treated as follows: control (5% sucrose, orally) and 20% ethanol (4 g/kg, orally) daily for 12 weeks. The BP (systolic, diastolic and mean) was recorded every week using the tail-cuff method. Six animals from each group were sacrificed at six, eight, 10 and 12 weeks after treatment, and blood was collected and analyzed.

RESULTS:

Systolic and mean BP were significantly elevated after six weeks, whereas diastolic BP was elevated after eight weeks of daily ethanol ingestion. BP elevation was related to a significant increase in plasma malondialdehyde and protein carbonyls, and a significant decrease in plasma NO, ratio of reduced to oxidized glutathione and the CuZn-superoxide dismutase and Mn-superoxide dismutase, catalase and glutathione peroxidase antioxidant enzyme activities in a time-dependent manner.

CONCLUSIONS:

The duration of alcohol ingestion is important in the induction of hypertension and the associated NO and antioxidant depletion, and oxidative tissue injury.     

2006 Ontario Survey on the Prevalence and Control of Hypertension (ON-BP): rationale and design of a community-based cross-sectional survey

BACKGROUND:

The presently available Canadian data, based on direct measurements of blood pressure (BP) from the Canadian Heart Health Surveys, are more than 15 years old. In view of major changes in the demographics and health status of the Ontario population, there is an urgent need to update this information. On the initiative of the Heart and Stroke Foundation of Ontario, the University of Ottawa Heart Institute, jointly with Statistics Canada, designed and implemented a population-based cross-sectional survey of hypertension in the Province of Ontario: the 2006 Ontario Survey on the Prevalence and Control of Hypertension (ON-BP).

OBJECTIVES:

To establish the prevalence of hypertension in the Ontario adult population between the ages of 20 and 79 years; to assess the awareness, current status and management of hypertension; and to gather respondent information about sex, age, physical measurements, personal health practices, socioeconomic measures, ethnicity and comorbidities.

METHODS:

The present paper describes the background history and the successive steps undertaken during the implementation of this project.

CONCLUSIONS:

The authors’ experiences from the ON-BP indicate that close co-operation between research scientists, statisticians, governmental and nongovernmental organizations – in the present case, the Heart and Stroke Foundation of Ontario – is essential to conduct a successful, large-scale survey of BP distribution.     

Aerobic Interval Exercise Training Induces Greater Reduction in Cardiac Workload in the Recovery Period in Rats

Background

Aerobic interval exercise training has greater benefits on cardiovascular function as compared with aerobic continuous exercise training.

Objective

The present study aimed at analyzing the effects of both exercise modalities on acute and subacute hemodynamic responses of healthy rats.

Methods

Thirty male rats were randomly assigned into three groups as follows: continuous exercise (CE, n = 10); interval exercise (IE, n = 10); and control (C, n = 10). Both IE and CE groups performed a 30-minute exercise session. The IE group session consisted of three successive 4-minute periods at 60% of maximal velocity (Max Vel), with 4-minute recovery intervals at 40% of Max Vel. The CE group ran continuously at 50% of Max Vel. Heart rate (HR), blood pressure(BP), and rate pressure product (RPP) were measured before, during and after the exercise session.

Results

The CE and IE groups showed an increase in systolic BP and RPP during exercise as compared with the baseline values. After the end of exercise, the CE group showed a lower response of systolic BP and RPP as compared with the baseline values, while the IE group showed lower systolic BP and mean BP values. However, only the IE group had a lower response of HR and RPP during recovery.

Conclusion

In healthy rats, one interval exercise session, as compared with continuous exercise, induced similar hemodynamic responses during exercise. However, during recovery, the interval exercise caused greater reductions in cardiac workload than the continuous exercise.     

Relationship between epistaxis and hypertension: A cause and effect or coincidence?

Introduction

Epistaxis is the most common otorhinolaryngological emergency. Whether there is an association or cause and effect relationship between epistaxis and hypertension is a subject of longstanding controversy.

Objective

The aim of our study is to evaluate the relationship between epistaxis and hypertension.

Materials and methods

This study was conducted at Olaya Medical Center (Riyadh) during the period between May 2013 and June 2014. A total of 80 patients were divided into two groups: Group A consisted of 40 patients who presented with epistaxis, and Group B consisted of 40 patients who served as a control group. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed for all patients. Patients were followed up for a period of three months.

Results

Readings of blood pressure (BP) were similar between the two groups regarding BP at presentation, ABPM, and BP at three months. There was a higher number of attacks in patients with history of hypertension. There was highly significant positive correlation between number of attacks of epistaxis and BP readings. Systolic BP at presentation was higher in patients who needed more complex interventions such as pack, balloon or cautery than those managed by first aid.

Conclusion

We found no definite association between epistaxis and hypertension. Epistaxis was not initiated by high BP but was more difficult to control in hypertensive patients.     

Prevalence,Awareness, and Management of CKD and Cardiovascular Risk Factors in Publicly Funded Health Care

Background and objectives

It is uncertain how many patients with CKD and cardiovascular risk factors in publicly funded universal health care systems are aware of their disease and how to achieve their treatment targets.

Design, setting, participants, & measurements

The CARTaGENE study evaluated BP, lipid, and diabetes profiles as well as corresponding treatments in 20,004 random individuals between 40 and 69 years of age. Participants had free access to health care and were recruited from four regions within the province of Quebec, Canada in 2009 and 2010.

Results

CKD (Chronic Kidney Disease Epidemiology Collaboration equation; <60 ml/min per 1.73 m²) was present in 4.0% of the respondents, and hypertension, diabetes, and hypercholesterolemia were reported by 25%, 7.4%, and 28% of participants, respectively. Self-awareness was low: 8% for CKD, 73% for diabetes, and 45% for hypercholesterolemia. Overall, 31% of patients with hypertension did not meet BP goals, and many received fewer antihypertensive drugs than appropriately controlled individuals; 41% of patients with diabetes failed to meet treatment targets. Among those patients with a moderate or high Framingham risk score, 53% of patients had LDL levels above the recommended levels, and many patients were not receiving a statin. Physician checkups were not associated with greater awareness but did increase the achievement of targets.

Conclusion

In this population with access to publicly funded health care, CKD and cardiovascular risk factors are common, and self-awareness of these conditions is low. Recommended targets were frequently not achieved, and treatments were less intensive in those patients who failed to reach goals. New strategies to enhance public awareness and reach guideline targets should be developed.     

Treatment and blood pressure control in 47,964 people with diabetes and hypertension: a systematic review of observational studies

BACKGROUND

Many patients with diabetes also have hypertension, greatly increasing their risk for cardiovascular disease. It has been suggested that hypertension is poorly treated in those with diabetes.

OBJECTIVE

To examine treatment and control of hypertension in people with diabetes.

DATA SOURCES

Data sources included MEDLINE, EMBASE, HealthSTAR, CINAHL, Web of Science, clinical evidence and government health and statistical Web sites.

METHOD

Databases were systematically reviewed and hand searches of the bibliographies of relevant studies (1990 to 2004) were conducted. Two investigators selected studies and extracted the data independently.

RESULTS

A total of 44 studies (77,649 subjects with diabetes, 47,964 [62%] of whom also had hypertension) were included. While 83% (range 32% to 100%) of patients with hypertension received drug therapy, only 12% (range 6% to 30%) had their blood pressure (BP) controlled to 130/85 mmHg or less. While BP control rates differed by definition of control (those studies with the least stringent definitions for BP control – 160/90 mmHg or less – reported mean control rates of 37%), treatment and control rates did not differ appreciably between countries or health care settings.

CONCLUSIONS

Fewer than one in eight people with diabetes and hypertension have adequately controlled BP, with remarkable uniformity across studies conducted in a variety of settings. There is an urgent need for multidisciplinary, community-based approaches to manage these high-risk patients.     

Blood Pressure Control and Left Ventricular Mass in Children with Chronic Kidney Disease

Summary

Background and objectives

Heart disease is a major cause of death in young adults with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) is common and is associated with hypertension. The aims of this study were to evaluate whether there is a relationship between LVH and BP in children with CKD and whether current targets for BP control are appropriate.

Design, setting, participants, & measurements

In this single-center cross-sectional study, 49 nonhypertensive children, (12.6 ± 3.0 years, mean GFR 26.1 ± 12.9 ml/min per 1.73 m²) underwent echocardiographic evaluation and clinic and 24-hour ambulatory BP monitoring. LVH was defined using age-specific reference intervals for left ventricular mass index (LVMI). Biochemical data and clinic BP for 18 months preceding study entry were also analyzed.

Results

The mean LVMI was 37.8 ± 9.1 g/m^2.7, with 24 children (49%) exhibiting LVH. Clinic BP values were stable over the 18 months preceding echocardiography. Patients with LVH had consistently higher BP values than those without, although none were overtly hypertensive (>95th percentile). Multiple linear regression demonstrated a strong relationship between systolic BP and LVMI. Clinic systolic BP showed a stronger relationship than ambulatory measures. Of the confounders evaluated, only elemental calcium intake yielded a consistent, positive relationship with LVMI.

Conclusions

LVMI was associated with systolic BP in the absence of overt hypertension, suggesting that current targets for BP control should be re-evaluated. The association of LVMI with elemental calcium intake questions the appropriateness of calcium-based phosphate binders in this population.     

Blood Pressure Monitoring Technique Impacts Hypertension Treatment

BACKGROUND

In 2005 the American Heart Association (AHA) released updated recommendations for blood pressure (BP) monitoring in order to ensure accurate BP measurements.

OBJECTIVE

To determine if current methods of BP assessment in an ambulatory clinic result in significantly different BP measurements than those obtained by following the AHA recommendations and if these BP differences impact treatment decisions.

RESEARCH DESIGN

Randomized prospective analysis.

SETTING

University of New Mexico Hospital Adult Internal Medicine clinic.

PATIENTS

Forty adults with hypertension

METHODS

Patient BPs were measured using both the traditional triage method and the AHA-recommended method in cross-over fashion in random order. Two complete medical profile summaries were then constructed for each patient: one for each BP measurement obtained by each technique. These profiles were then reviewed by a panel of providers who provided hypothetical hypertension treatment recommendations.

RESULTS

Individual BP results varied greatly between the two methods. SBP readings differed by ≥5 mmHg in either direction for 68% of patients while 78% of patient’s DBP readings differed by ≥2 mmHg in either direction. Overall, 93% of patients had a BP difference of either ≥5 mmHg systolic or ≥2 mmHg diastolic. Five patients were determined to be at goal with the triage method, but were higher than their goal BP with the AHA method Significant differences were also seen in treatment recommendations for a given patient based on the differences seen between the two obtained BP readings. The number of patients with treatment variations between their two profiles ranged from 13% to 23% depending on the reviewing provider (p < 0.01 for all providers).

CONCLUSION

Inaccurate BP assessment is common and may impact hypertension treatment decisions.KEY WORDS: blood pressure measurement, hypertension     

Effect of Exercise on Blood Pressure in Type 2 Diabetes: A Randomized Controlled Trial

BACKGROUND

Increased blood pressure (BP) in type 2 diabetes (T2DM) markedly increases cardiovascular disease morbidity and mortality risk compared to having increased BP alone.

OBJECTIVE

To investigate whether exercise reduces suboptimal levels of untreated suboptimal BP or treated hypertension.

DESIGN

Prospective, randomized controlled trial for 6 months.

SETTING

Single center in Baltimore, MD, USA.

PATIENTS

140 participants with T2DM not requiring insulin and untreated SBP of 120–159 or DBP of 85–99 mmHg, or, if being treated for hypertension, any SBP <159 mmHg or DBP < 99 mmHg; 114 completed the study.

INTERVENTION

Supervised exercise, 3 times per week for 6 months compared with general advice about physical activity.

MEASUREMENTS

Resting SBP and DBP (primary outcome); diabetes status, arterial stiffness assessed as carotid-femoral pulse-wave velocity (PWV), body composition and fitness (secondary outcomes).

RESULTS

Overall baseline BP was 126.8 ± 13.5 / 71.7 ± 9.0 mmHg, with no group differences. At 6 months, BP was unchanged from baseline in either group, BP 125.8 ± 13.2 / 70.7 ± 8.8 mmHg in controls; and 126.0 ± 14.2 / 70.3 ± 9.0 mmHg in exercisers, despite attaining a training effects as evidenced by increased aerobic and strength fitness and lean mass and reduced fat mass (all p < 0.05), Overall baseline PWV was 959.9 ± 333.1 cm/s, with no group difference. At 6-months, PWV did not change and was not different between group; exercisers, 923.7 ± 319.8 cm/s, 905.5 ± 344.7, controls.

LIMITATIONS

A completion rate of 81 %.

CONCLUSIONS

Though exercisers improve fitness and body composition, there were no reductions in BP. The lack of change in arterial stiffness suggests a resistance to exercise-induced BP reduction in persons with T2DM.KEY WORDS: exercise training, diabetes, high blood pressure, randomized trial     

Relationship between blood pressure and incident chronic kidney disease in hypertensive patients

Summary

Background and objectives

Hypertension is an important cause of chronic kidney disease (CKD). Identifying risk factors for progression to CKD in patients with normal kidney function and hypertension may help target therapies to slow or prevent decline of kidney function. Our objective was to identify risk factors for development of incident CKD and decline in estimated GFR (eGFR) in hypertensive patients.

Design, setting, participants, & measurements

Cox proportional hazards models were used to assess the relationship between incident CKD (defined as eGFR <60 ml/min per 1.73 m²) and potential risk factors for CKD from a registry of hypertensive patients.

Results

Of 43,305 patients meeting the inclusion criteria, 12.1% (5236 patients) developed incident CKD. Diabetes was the strongest predictor of incident CKD (hazard ratio, 1.96; 95% confidence interval, 1.84 to 2.09) and was associated with the greatest rate of decline in eGFR (−2.2 ml/min per 1.73 m² per year). Time-varying systolic BP was associated with incident CKD with risk increasing above 120 mmHg; each 10-mmHg increase in baseline and time-varying systolic BP was associated with a 6% increase in the risk of developing CKD (hazard ratio, 1.06; 95% confidence interval, 1.04 to 1.08 for both). Time-weighted systolic BP was associated with a more rapid decline in eGFR of an additional 0.2 ml/min per 1.73 m² per year decline for every 10-mmHg increase in systolic BP.

Conclusions

We found that time-varying systolic BP was associated with incident CKD, with an increase in risk above a systolic BP of 120 mmHg among individuals with hypertension.     

Masked Hypertension and Elevated Nighttime Blood Pressure in CKD: Prevalence and Association with Target Organ Damage

Background and objectives

Masked hypertension and elevated nighttime BP are associated with increased risk of hypertensive target organ damage and adverse cardiovascular and renal outcomes in patients with normal kidney function. The significance of masked hypertension for these risks in patients with CKD is less well defined. The objective of this study was to evaluate the association between masked hypertension and kidney function and markers of cardiovascular target organ damage, and to determine whether this relationship was consistent among those with and without elevated nighttime BP.

Design, setting, participants, & measurements

This was a cross-sectional study. We performed 24-hour ambulatory BP in 1492 men and women with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. We categorized participants into controlled BP, white-coat, masked, and sustained hypertension on the basis of clinic and 24-hour ambulatory BP. We obtained echocardiograms and measured pulse wave velocity in 1278 and 1394 participants, respectively.

Results

The percentages of participants with controlled BP, white-coat, masked, and sustained hypertension were 49.3%, 4.1%, 27.8%, and 18.8%, respectively. Compared with controlled BP, masked hypertension independently associated with low eGFR (−3.2 ml/min per 1.73 m²; 95% confidence interval, −5.5 to −0.9), higher proteinuria (+0.9 unit higher in log₂ urine protein; 95% confidence interval, 0.7 to 1.1), and higher left ventricular mass index (+2.52 g/m^2.7; 95% confidence interval, 0.9 to 4.1), and pulse wave velocity (+0.92 m/s; 95% confidence interval, 0.5 to 1.3). Participants with masked hypertension had lower eGFR only in the presence of elevated nighttime BP (−3.6 ml/min per 1.73 m²; 95% confidence interval, −6.1 to −1.1; versus −1.4 ml/min per 1.73 m²; 95% confidence interval, −6.9 to 4.0, among those with nighttime BP <120/70 mmHg; P value for interaction with nighttime systolic BP 0.002).

Conclusions

Masked hypertension is common in patients with CKD and associated with lower eGFR, proteinuria, and cardiovascular target organ damage. In patients with CKD, ambulatory BP characterizes the relationship between BP and target organ damage better than BP measured in the clinic alone.     

Asymmetric and Symmetric Dimethylarginine and Sympathetic Nerve Traffic after Renal Denervation in Patients with Resistant Hypertension

Background and objectives

The plasma concentration of the endogenous inhibitor of nitric oxide synthase asymmetric dimethylarginine (ADMA) associates with sympathetic activity in patients with CKD, but the driver of this association is unknown.

Design, setting, participants, & measurements

In this longitudinal study (follow-up: 2 weeks–6 months), repeated measurements over time of muscle sympathetic nerve activity corrected (MSNAC), plasma levels of ADMA and symmetric dimethylarginine (SDMA), and BP and heart rate were performed in 14 patients with drug-resistant hypertension who underwent bilateral renal denervation (enrolled in 2013 and followed-up until February 2014). Stability of ADMA, SDMA, BP, and MSNAC over time (6 months) was assessed in two historical control groups of patients maintained on stable antihypertensive treatment.

Results

Time-integrated changes in MSNAC after renal denervation ranged from –40.6% to 10% (average, –15.1%), and these changes were strongly associated with the corresponding changes in plasma ADMA (r= 0.62, P=0.02) and SDMA (r=0.72, P=0.004). Changes in MSNAC went along with simultaneous changes in standardized systolic (r=0.65, P=0.01) and diastolic BP (r=0.61, P=0.02). In the historical control groups, no change in ADMA, SDMA, BP, and MSNAC levels was recorded during a 6-month follow-up.

Conclusions

In patients with resistant hypertension, changes in sympathetic activity after renal denervation associate with simultaneous changes in plasma levels of the two major endogenous methylarginines, ADMA and SDMA. These observations are compatible with the hypothesis that the sympathetic nervous system exerts an important role in modulating circulating levels of ADMA and SDMA in this condition.     

Intradialytic Hypertension and its Association with Endothelial Cell Dysfunction

Summary

Background and objectives

Intradialytic hypertension is associated with adverse outcomes, yet the mechanism is uncertain. Patients with intradialytic hypertension exhibit imbalances in endothelial-derived vasoregulators nitric oxide and endothelin-1, indirectly suggesting endothelial cell dysfunction. We hypothesized that intradialytic hypertension is associated in vivo with endothelial cell dysfunction, a novel predictor of adverse cardiovascular outcomes.

Design, settings, participants, & measurements

We performed a case-control cohort study including 25 hemodialysis (HD) subjects without (controls) and 25 with intradialytic hypertension (an increase in systolic BP pre- to postdialysis ≥10 mmHg ≥4/6 consecutive HD sessions). The primary outcome was peripheral blood endothelial progenitor cells (EPCs) assessed by aldehyde dehydrogenase activity (ALDH^br) and cell surface marker expression (CD34⁺CD133⁺). We also assessed endothelial function by ultrasonographic measurement of brachial artery flow-mediated vasodilation (FMD) normalized for shear stress. Parametric and nonparametric t tests were used to compare EPCs, FMD, and BP.

Results

Baseline characteristics and comorbidities were similar between groups. Compared with controls, 2-week average predialysis systolic BP was lower among subjects with intradialytic hypertension (144.0 versus 155.5 mmHg), but postdialysis systolic BP was significantly higher (159.0 versus 128.1 mmHg). Endothelial cell function was impaired among subjects with intradialytic hypertension as measured by decreased median ALDH^br cells and decreased CD34⁺CD133⁺ cells (ALDH^br, 0.034% versus 0.053%; CD34⁺CD133⁺, 0.033% versus 0.059%). FMD was lower among subjects with intradialytic hypertension (1.03% versus 1.67%).

Conclusions

Intradialytic hypertension is associated with endothelial cell dysfunction. We propose that endothelial cell dysfunction may partially explain the higher event rates observed in these patients.     

A Successful Multifaceted Trial to Improve Hypertension Control in Primary Care: Why Did it Work?

Background

It is important to understand which components of successful multifaceted interventions are responsible for study outcomes, since some components may be more important contributors to the intervention effect than others.

Objective

We conducted a mediation analysis to determine which of seven factors had the greatest effect on change in systolic blood pressure (BP) after 6 months in a trial to improve hypertension control.

Design

The study was a preplanned secondary analysis of a cluster-randomized clinical trial. Eight clinics in an integrated health system were randomized to provide usual care to their patients (n = 222), and eight were randomized to provide a telemonitoring intervention (n = 228).

Participants

Four hundred three of 450 trial participants completing the 6-month follow-up visit were included.

Interventions

Intervention group participants received home BP telemonitors and transmitted measurements to pharmacists, who adjusted medications and provided advice to improve adherence to medications and lifestyle modification via telephone visits.

Main measures

Path analytic models estimated indirect effects of the seven potential mediators of intervention effect (defined as the difference between the intervention and usual care groups in change in systolic BP from baseline to 6 months). The potential mediators were change in home BP monitor use, number of BP medication classes, adherence to BP medications, physical activity, salt intake, alcohol use, and weight.

Key Results

The difference in change in systolic BP was 11.3 mmHg. The multivariable mediation model explained 47 % (5.3 mmHg) of the intervention effect. Nearly all of this was mediated by two factors: an increase in medication treatment intensity (24 %) and increased home BP monitor use (19 %). The other five factors were not significant mediators, although medication adherence and salt intake improved more in the intervention group than in the usual care group.

Conclusions

Most of the explained intervention effect was attributable to the combination of self-monitoring and medication intensification. High adherence at baseline and the relatively low intensity of resources directed toward lifestyle change may explain why these factors did not contribute to the improvement in BP.KEY WORDS: Blood pressure, Hypertension, Randomized trial, Mediation, Telemonitoring, Case management     

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

BACKGROUND:

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.

OBJECTIVES:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.