Effect of telmisartan 80 mg once daily on 24-h blood pressure profile in patients with mild-to-moderate hypertension failing to respond to prior antihypertensive therapy

Blood pressure is not adequately controlled in almost 50% of patients with hypertension who are in receipt of antihypertensive therapy. This multicentre, prospective, open-label trial was designed to determine whether or not once-daily telmisartan 80 mg reduced blood pressure during the last 6 h of the 24-h dosing interval in patients with mild-to-moderate hypertension who were unresponsive to previous antihypertensive therapy. The study comprised 100 patients (47 males, 53 females) who had failed to respond satisfactorily to prior treatment given for a minimum of 3 months. At screening, 24-h ambulatory blood pressure monitoring (ABPM) was conducted after the patient had been treated with the currently prescribed antihypertensive medication. Following 5 weeks of telmisartan 80 mg treatment, ABPM was repeated. Telmisartan significantly reduced mean systolic blood pressure, diastolic blood pressure (DBP) and pulse pressure compared with previous antihypertensive therapy over each time interval (24-h, morning, night-time and the last 6 h of the dosing interval [2.00 a.m.-8.00 a.m.]) analysed. In addition, more than 90% of patients responded successfully (clinic DBP <90 mmHg or a >10 mmHg reduction in clinic DBP) at the end of telmisartan treatment. In conclusion, telmisartan provides effective blood pressure control throughout the 24-h dosing interval in patients with mild-to-moderate hypertension who were unresponsive to previous antihypertensive medication.     

Short Sleep Duration Is Associated With a Blood Pressure Nondipping Pattern in Type 1 Diabetes: The DIAPASOM study

OBJECTIVE

To assess whether nocturnal blood pressure dipping status in type 1 diabetes is correlated with specific sleep characteristics and differences in nocturnal glycemic profiles.

RESEARCH DESIGN AND METHODS

Twenty type 1 diabetic adult patients underwent sleep studies with simultaneous 24-h ambulatory blood pressure monitoring and continuous nocturnal glucose monitoring.

RESULTS

Altogether, 55% of patients exhibited blunted blood pressure dipping. They did not differ from the dipper group in age, BMI, or systolic (SBP) and diastolic (DBP) blood pressure. Total sleep period (TSP) was higher in the dipper group (497 ± 30 vs. 407 ± 44 min for dippers and nondippers, respectively, P < 0.001). TSP was correlated with SBP and DBP day-night differences (r = 0.44 and 0.49, respectively). Periods of nocturnal hypoglycemia (i.e., % of TSP with glycemia <70 mg/dl) were longer in the dipper group (8.1 ± 10.7 vs. 0.1 ± 0.4% for dippers and nondippers, respectively, P = 0.02).

CONCLUSIONS

Dipping status in type 1 diabetes was associated with longer sleep duration and with hypoglycemia unawareness.During sleep, ambulatory blood pressure monitoring (ABPM) demonstrates a normal decline of over 10% in blood pressure (BP), corresponding to the so-called dipping status. In type 1 diabetes, nondipping status is more prevalent (1) and is associated with increased risks for sustained hypertension, retinopathy, and nephropathy (1–3). Dipping pattern could be influenced by sleep duration and associated sleep disorders (4). In type 1 diabetes, sleep stability impacts sleep-related hypoglycemia by changing awakening responses to these episodes (5). Our hypothesis was that type 1 diabetic subjects with more stable sleep could exhibit normal BP dip and, because of higher arousal thresholds, could present an increased frequency of nocturnal hypoglycemia.     

Fixed-Dose Triple Combination of Antihypertensive Drugs Improves Blood Pressure Control: From Clinical Trials to Clinical Practice

Introduction

Blood pressure (BP) control is the main clinical goal in the management of hypertensive patients; however, BP in most of these patients remains uncontrolled, despite the widespread availability of antihypertensive drugs as free-combination therapy. This study compared the efficacy of a fixed-dose triple combination (FDTC) of antihypertensive drugs with that of a free combination of three antihypertensives in patients with uncontrolled hypertension.

Methods

Ninety-two patients (mean age 60.8 ± 12.1, 58.0% male) with uncontrolled essential hypertension (office systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg) previously treated with a renin–angiotensin–aldosterone system (RAAS) inhibitor plus hydrochlorothiazide were switched to once-daily FDTC therapy with perindopril/indapamide/amlodipine (5–10/1.25–2.5/5–10 mg). Patients were age- and sex-matched with a control group of hypertensive patients receiving free-combination therapy with three drugs including a RAAS inhibitor, a diuretic, and a calcium channel blocker. Office BP and 24-h ambulatory BP monitoring (ABPM) were evaluated at baseline and after 1 and 4 months.

Results

Significant reductions in ambulatory 24-h, daytime, and nighttime systolic BP, and pulse pressure (PP) were found in the FDTC group relative to reductions seen with free-combination therapy, after the first month only of follow-up. Target BP values (mean 24-h ambulatory systolic/diastolic BP < 130/80 mmHg) were reached by more recipients of FDTC than free-combination therapy (64.8% vs. 46.9%, p < 0.05) at month 4 of follow-up, despite reductions in 24-h ABPM values from baseline being similar in both groups at this time point.

Conclusion

FDTC of perindopril/indapamide/amlodipine was effective at reducing SBP and PP in previously treated patients with uncontrolled hypertension, and well tolerated, providing support for clinicians in choosing a fixed-dose triple combination over the free-combination of a RAAS inhibitor, a diuretic, and a calcium antagonist.

     

Short Sleep Duration Measured by Wrist Actimetry Is Associated With Deteriorated Glycemic Control in Type 1 Diabetes

OBJECTIVE

Sleep restriction has been associated with deteriorated insulin sensitivity. The effects of short sleep duration have been explored little in patients with type 1 diabetes. This study addresses the question of whether sleep curtailment affects HbA_1c levels in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS

Seventy-nine adult patients with type 1 diabetes (median age 40 years [IQR 23–49]; 47% men) were recruited to wear a wrist actimetry sensor during 3 consecutive days to assess mean sleep duration during normal daily life. A subsample of 37 patients also performed 24-h ambulatory blood pressure monitoring (ABPM). Medical history, sleep questionnaires, and diabetes-related quality of life (DQOL) were assessed.

RESULTS

Patients having shorter sleep duration—less than 6.5 h (n = 21)—had higher levels of HbA_1c (P = 0.01) than patients with longer sleep duration, above 6.5 h (n = 58). In a multivariable regression model including shorter versus longer sleep duration, diabetes duration, DQOL score, and daily activity, sleep duration was the only variable independently associated with HbA_1c (R² = 10%). In patients who performed 24-h ABPM, patients with a nondipping pattern of blood pressure exhibited shorter sleep duration than patients with a dipping pattern of blood pressure.

CONCLUSIONS

Shorter sleep duration is associated with higher HbA_1c levels in patients with type 1 diabetes, as well as with a nondipping pattern of blood pressure, anticipating a long-term deleterious impact on the risk of microvascular complications. Further studies should test whether extending the duration of sleep may improve both HbA_1c and blood pressure in type 1 diabetes.Voluntary sleep curtailment is spreading among our societies, particularly in children and adolescents (1). Such chronic sleep deprivation is also frequent among patients suffering from type 1 diabetes as well as their families (2). Several prospective cohorts in the general population demonstrate a link between short sleep duration and incident obesity (3), type 2 diabetes (4–6), and hypertension (7,8). The main weakness of these studies, which were conducted with large samples, is that sleep duration was not objectively assessed but only estimated subjectively by sleep questionnaires. Mechanisms underlying such associations seem to involve down-regulation of the satiety hormone leptin and up-regulation of the appetite-stimulating hormone ghrelin, increasing hunger and food intake (9). Sleep restriction has been associated with deterioration of insulin sensitivity (10).The effects of short sleep duration have been poorly explored in patients with type 1 diabetes. Short sleep duration has been associated with a nondipping pattern of blood pressure in patients with type 1 diabetes (11), which means that nocturnal blood pressure did not demonstrate the normal 10% decrease compared with daytime values. No study has yet addressed the question of the potential deleterious effect of sleep curtailment on HbA_1c in type 1 diabetes. Priou et al. (12) recently have shown that sleep apnea syndrome (obstructive sleep apnea [OSA]) was associated with increased levels of HbA_1c in subjects with OSA but without any diabetes, suggesting that sleep respiratory disorders could alter plasma glucose levels; however, this work did not evaluate the potential association of total sleep time with HbA_1c.Strict control of HbA_1c and blood pressure levels, including the normal dip of nocturnal blood pressure, have been clearly associated with lower incidence of microvascular complications in type 1 diabetes (13–15). Thus, this study looked for the effects of sleep duration on glycemic control and nocturnal blood pressure patterns in patients with type 1 diabetes.     

The Antihypertensive Efficacy of the Triple Fixed Combination of Perindopril,Indapamide, and Amlodipine: The Results of the PETRA Study

Introduction

The etiology of essential hypertension is multifactorial. Therefore, treatment with combinations of antihypertensive agents acting on multiple targets is necessary for successful therapy in the majority of patients. According to the experience and clinical data accumulated so far, combination therapy with three agents from different pharmacological classes is required in approx. 30% of patients in order to achieve long-term blood pressure control. The primary objective of the PETRA study was to evaluate the efficacy of blood pressure (BP) control with once daily administration of the different dosage strengths of the once-daily, triple fixed combination of perindopril, indapamide, and amlodipine. The evaluation was based on office BP readings and ambulatory blood pressure monitoring (ABPM) data gathered in routine clinical practice.

Methods

Data from 11,209 hypertensive patients (the proportion of female subjects was 47.6%) were processed and interpreted in a 3-month-long prospective, observational, non-interventional, open-label study conducted in 997 centers in Hungary.

Results

Mean baseline office BP was 156.58 ± 16.10/91.56 ± 9.33 mmHg (mean ± SD), whereas the mean duration of hypertension was 9.48 ± 7.19 years. Mean office BP decreased by 24.81 ± 15.47/11.41 ± 9.90 mmHg after switching to the triple fixed combination of perindopril, indapamide, and amlodipine (p < 0.0001). At the final visit 45.1% of patients took the 5/1.25/5 mg, 33.5% of them 10/2.5/5 mg, and 21.4% of them 10/2.5/10 mg strength of the perindopril/indapamide/amlodipine triple fixed combination. The 24-h blood pressure was obtained in 76 subjects. The mean 24-h BP decreased from 155.51 ± 17.43/85.28 ± 11.48 to 134.63 ± 12.51/77.83 ± 8.99 mmHg (p < 0.0001). Statistically significant (p < 0.0001) and clinically relevant improvement of a number of metabolic parameters—including total cholesterol (?8.6%), LDL-cholesterol (?11.4%), triglyceride (?12.1%), and fasting blood glucose (?6.6%) levels—was observed over the 3-month study period.

Conclusions

During the 3 months of the PETRA study, the outstanding 24-h antihypertensive efficacy of the triple fixed combination of perindopril, indapamide, and amlodipine was confirmed both by office BP readings and by ABPM recordings. This combination may offer a new therapeutic option for hypertensive patients who have failed to achieve the desired BP target on their previous dual combination therapy.

Funding

EGIS Pharmaceuticals PLC.

     

Disparities in antihypertensive medication adherence in persons with disabilities and without disabilities: results of a Korean population-based study

Park JH, Park JH, Lee SY, Kim SY, Shin Y, Kim SY. Disparities in antihypertensive medication adherence in persons with disabilities and without disabilities: results of a Korean population-based study.

Objective

To determine disparities in antihypertensive medication adherence between persons with disabilities and those without disabilities in South Korea.

Design

The study compared antihypertensive medication adherence between persons with disabilities and those without disabilities using medical claims data of the National Health Insurance (NHI).

Setting

We obtained data from claims submitted to the NHI, which covers almost the entire Korean population. Persons who were prescribed antihypertensive medication during the calendar year 2004 were identified.

Participants

The study comprised data from persons with disabilities (n=85,098) and persons without disabilities (n=2,368,636).

Interventions

Not applicable.

Main Outcome Measures

A cumulative medication adherence (CMA) greater than or equal to 80% was defined as an appropriate medication adherence. Multiple logistic regression was used to identify differences in antihypertensive medication adherence between persons with disabilities and without disabilities. Estimates were adjusted for demographic characteristics (sex, age), type of medical insurance, insurance contribution a month as a proxy for household income, residential area, and clinical characteristics (medication duration, comorbid conditions).

Results

People with disabilities had lower CMAs than those without (median CMA, 83.6% vs 85.7%; appropriate medication adherence, 54.5% vs 57.5%). Results of the multiple logistic regression adjusting other factors indicated that people with disabilities had decreased probabilities of appropriate adherence.

Conclusions

Medication adherence is reduced by various types of disability and impairment such as those involving mobility and communication. Much effort should be made to investigate how and why these disparities take place and develop health policies to remove these disparities if they exist.     

Insufficient Control of Blood Pressure and Incident Diabetes

OBJECTIVE

Incidence of type 2 diabetes might be associated with preexisting hypertension. There is no information on whether incident diabetes is predicted by blood pressure control. We evaluated the hazard of diabetes in relation to blood pressure control in treated hypertensive patients.

RESEARCH DESIGN AND METHODS

Nondiabetic, otherwise healthy, hypertensive patients (N = 1,754, mean ± SD age 52 ± 11 years, 43% women) participated in a network over 3.4 ± 1 years of follow-up. Blood pressure was considered uncontrolled if systolic was ≥140 mmHg and/or diastolic was ≥90 mmHg at the last outpatient visit. Diabetes was defined according to American Diabetes Association guidelines.

RESULTS

Uncontrolled blood pressure despite antihypertensive treatment was found in 712 patients (41%). At baseline, patients with uncontrolled blood pressure were slightly younger than patients with controlled blood pressure (51 ± 11 vs. 53 ± 12 years, P < 0.001), with no differences in sex distribution, BMI, duration of hypertension, baseline blood pressure, fasting glucose, serum creatinine and potassium, lipid profile, or prevalence of metabolic syndrome. During follow-up, 109 subjects developed diabetes. Incidence of diabetes was significantly higher in patients with uncontrolled (8%) than in those with controlled blood pressure (4%, odds ratio 2.08, P < 0.0001). In Cox regression analysis controlling for baseline systolic blood pressure and BMI, family history of diabetes, and physical activity, uncontrolled blood pressure doubled the risk of incident diabetes (hazard ratio [HR] 2.10, P < 0.001), independently of significant effects of age (HR 1.02 per year, P = 0.03) and baseline fasting glucose (HR 1.10 per mg/dl, P < 0.001).

CONCLUSIONS

In a large sample of treated nondiabetic hypertensive subjects, uncontrolled blood pressure is associated with twofold increased risk of incident diabetes independently of age, BMI, baseline blood pressure, or fasting glucose.Arterial hypertension is common in patients with type 2 diabetes. A survey of over 1,500 patients with diabetes, conducted between 1988 and 1994, determined that 60–80% had blood pressure higher than 130/85 mmHg or had been prescribed antihypertensive medication (1). Results from MRFIT (Multiple Risk Factor Intervention Trial) indicated that diabetes confers greater cardiovascular risk for comparable levels of other cardiovascular risk factors, suggesting that blood pressure control should be more rigorous in the presence of diabetes (2). However, there is no clearly defined temporal relationship between diabetes and hypertension.Incidence of type 2 diabetes, in fact, also increases with increased baseline blood pressure in women without prevalent diabetes, based on modified blood pressure categories from the 2007 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines (3). There is increasing evidence of a substantial interplay of metabolic factors with arterial hypertension (4,5). We have recently shown that optimal control of blood pressure is blunted by coexisting metabolic risk factors, clustering the phenotype of metabolic syndrome (4). There is no information about whether suboptimal control of blood pressure might also be associated with incident diabetes, independently of confounders. Accordingly, we tested the hypothesis that insufficient control of blood pressure is an independent risk factor for diabetes in a cohort of hypertensive patients with initial normal fasting plasma glucose.     

Deleterious Associations of Sitting Time and Television Viewing Time With Cardiometabolic Risk Biomarkers: Australian Diabetes, Obesity and Lifestyle (AusDiab) study 2004�C2005

OBJECTIVE

We examined the associations of sitting time and television (TV) viewing time with continuously measured biomarkers of cardio-metabolic risk in Australian adults.

RESEARCH DESIGN AND METHODS

Waist circumference, BMI, resting blood pressure, triglycerides, HDL cholesterol, fasting and 2-h postload plasma glucose, and fasting insulin were measured in 2,761 women and 2,103 men aged ≥30 years (mean age 54 years) without clinically diagnosed diabetes from the 2004–2005 Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Multivariate linear regression analyses examined associations of self-reported sitting time and TV viewing time (hours per day) with these biomarkers, adjusting for potential confounding variables.

RESULTS

For both women and men, sitting time was detrimentally associated with waist circumference, BMI, systolic blood pressure, fasting triglycerides, HDL cholesterol, 2-h postload plasma glucose, and fasting insulin (all P < 0.05), but not with fasting plasma glucose and diastolic blood pressure (men only). With the exception of HDL cholesterol and systolic blood pressure in women, the associations remained significant after further adjustment for waist circumference. TV viewing time was detrimentally associated with all metabolic measures in women and all except HDL cholesterol and blood pressure in men. Only fasting insulin and glucose (men only) remained deleteriously associated with TV viewing time after adjustment for waist circumference.

CONCLUSIONS

In women and men, sitting time and TV viewing time were deleteriously associated with cardio-metabolic risk biomarkers, with sitting time having more consistent associations in both sexes and being independent of central adiposity. Preventive initiatives aimed at reducing sitting time should focus on both nonleisure and leisure-time domains.Sitting is ubiquitous in adults'' daily routines: watching television (TV), using computers, performing desk-bound occupational tasks, and commuting by automobile (1). The majority of studies on the metabolic consequences of sitting time have focused on associations with leisure-time sitting, primarily TV viewing time. High levels of TV viewing are associated with elevated risk of obesity, type 2 diabetes, and abnormal glucose metabolism (2–4); additionally, detrimental associations have been observed with continuous measures of glucose and insulin in healthy adults (5) and with waist circumference and systolic blood pressure in physically active men and women (4). Associations have generally been stronger and more consistent in women than in men (2,3).Prolonged sitting time is highly prevalent in contexts other than domestic TV viewing, including occupational sitting, which has been shown to be positively associated with a higher BMI, particularly in men (6). Studies examining sitting time across the whole day (including both leisure- and nonleisure contexts) have reported significant associations with overweight and obesity and with weight gain (7,8). However, the extent to which overall sitting time is associated with biomarkers of cardiovascular and diabetes risk has not been investigated. Furthermore, the extent to which both sitting and TV viewing time influence continuous measures of metabolic risk in the same population has not been explored.We examined concurrently the associations of sitting time and TV viewing time with biomarkers of cardio-metabolic risk (waist circumference, BMI, systolic and diastolic blood pressure, fasting serum triglycerides, HDL cholesterol, fasting and 2-h postload plasma glucose, and fasting serum insulin) in a large population-based sample of Australian women and men without diagnosed diabetes.     

Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes

OBJECTIVE

We prospectively investigated in hypertensive patients with type 2 diabetes if bedtime treatment with ≥1 hypertension medications exerts better blood pressure control and cardiovascular risk reduction than conventional therapy, in which all medications are ingested in the morning.

RESEARCH DESIGN AND METHODS

We conducted a prospective, randomized, open-label, blinded end point trial on 448 hypertensive patients with type 2 diabetes, 255 men/193 women, mean ± SD age 62.5 ± 10.8 years, randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. Ambulatory blood pressure was measured for 48 h at baseline and again annually or even more frequently (quarterly) after adjustments in treatment.

RESULTS

After a median follow-up of 5.4 years, patients ingesting ≥1 hypertension medications at bedtime showed a significantly lower cardiovascular risk (adjusted by age and sex) than subjects ingesting all medications upon awakening (hazard ratio 0.33 [95% CI 0.21–0.54]; P < 0.001). The difference between groups in the adjusted risk of major events (cardiovascular death, myocardial infarction, and stroke) was also statistically significant (0.25 [0.10–0.61]; P = 0.003). Patients treated at bedtime showed significantly lower sleep time blood pressure mean and higher prevalence of controlled ambulatory blood pressure (62.5 vs. 50.9%; P = 0.013). There was a significant 12% cardiovascular risk reduction per each 5 mmHg decrease in asleep systolic blood pressure during follow-up (P < 0.001).

CONCLUSIONS

Among patients with diabetes, treatment with ≥1 hypertension medications at bedtime, compared with all medications upon waking, resulted in improved ambulatory blood pressure control and significantly reduced cardiovascular morbidity and mortality.A number of published prospective trials reviewed elsewhere (1) have reported clinically meaningful morning/evening treatment time differences in blood pressure lowering efficacy, duration of action, safety profile, and/or effects on the circadian blood pressure pattern for different classes of hypertension medications. For instance, a once-daily evening, in comparison with morning, ingestion schedule of angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) results in greater therapeutic effect on asleep blood pressure, independent of the terminal half-life of each individual medication (1).The impact of bedtime chronotherapy on sleep time blood pressure regulation might be of clinical importance. This perspective is based on the growing number of studies, all concerning ambulatory blood pressure monitoring (ABPM), that have consistently shown an association between blunted sleep time blood pressure decline and increased incidence of cardiovascular disease (CVD) events, both in subjects without (2–4) as well as with diabetes (5–7). Independent prospective studies have also found that the sleep time blood pressure mean is a better predictor of CVD risk than the daytime or 24-h blood pressure mean (3,8–12), a relevant finding also documented for patients with diabetes (13–15). Nocturnal hypertension is not only frequent but also highly predominant in patients with diabetes (6,7,13–15). A limitation of all of these previous studies on the prognostic value of nighttime blood pressure is their reliance on a single baseline ABPM profile from each participant at the time of inclusion, without accounting for changes in the blood pressure pattern or level during the years of follow-up. Thus, the potential reduction in CVD risk associated with specifically reducing sleep time blood pressure, which has been found to be much more feasible by bedtime than by upon waking dosing of conventional hypertension medications (1), is still a matter of debate.The MAPEC (Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares [Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events]) study was specifically designed to investigate prospectively whether bedtime treatment with ≥1 hypertension medications exerts significantly better blood pressure control and CVD risk reduction than conventional therapy, in which all medications are ingested upon waking (16,17). We here report results on the differential effect of blood pressure–lowering chronotherapy on CVD risk in hypertensive patients with type 2 diabetes.     

Multicenter Randomized Double-Blind Comparison of Nebivolol plus HCTZ and Irbesartan plus HCTZ in the Treatment of Isolated Systolic Hypertension in Elderly Patients: Results of the NEHIS Study

Introduction

The present study was aimed at comparing the antihypertensive efficacy, tolerability, and side effects profile of nebivolol/hydrochlorothiazide (NH) vs irbesartan/hydrochlorothiazide (IH) combination in elderly patients with isolated systolic hypertension (ISH).

Methods

124 ISH patients aged 69.1 ± 5.1 years (mean ± SD) were enrolled by 13 general practitioners in Netherlands and Belgium and randomized in a double-blind fashion to receive either NH (5/12.5 mg day, n = 62) or IH (150/12.5 mg day, n = 62) for a 12-week period. The primary efficacy endpoint of the study was the comparison of the two combinations in terms of sitting office systolic blood pressure (BP) reduction after 12 weeks of treatment. In addition ambulatory BP, 24-h BP variability, tolerability, and safety profile were also investigated.

Results

122 patients were included in the intention-to-treat analysis. After 12 weeks of treatment the reduction of systolic BP with NH was significantly greater than IH (?25.8 ± 12 vs ?21.2 ± 14 mm Hg, P < 0.03). Diastolic BP reduction was significantly greater with NH after 4 and 8 weeks of treatment but similar at the end of the study (or after 12 weeks). In contrast, the magnitude of the 24-h, daytime, and nighttime systolic and diastolic BP reduction was almost similar in the two groups, while heart rate reduction induced by NH was significantly (P < 0.001) greater during the 24-h, daytime, and nighttime period than that induced by IH. NH caused a reduction in 24-h BP variability significantly greater than IH (standard deviation ?4.4 ± 2.7 vs ?2.2 ± 5.1 mm Hg, P < 0.02, variation coefficient ?2.0 ± 2.6 vs ?0.3 ± 3.4%, P < 0.01). Both treatment regimens were well tolerated.

Conclusions

These data provide evidence that NH reduces office BP more than IH but has similar effects on 24-h BP. NH reduces 24-h systolic and diastolic BP variability more than IH, suggesting a greater protective effect on a variable known to adversely affect prognosis.

Trial Registration

EU clinical Trials Register identifier, 2010-023104-28.

Funding

Menarini International Operations Luxembourg.

     

Efficacy/Safety of Olmesartan Medoxomil Versus Losartan Potassium in Na?ve Versus Previously Treated Subjects With Hypertension

Introduction

A predefined exploratory analysis of a prospective, randomized, double-blind, forcedtitration study of olmesartan medoxomil (OM) versus losartan potassium (LOS) in subjects with hypertension not previously or previously treated with antihypertensive medication is reported.

Methods

The study included a 3?C4-week placebo run-in and an 8-week active treatment period: OM (weeks 1?C4, OM 20 mg; weeks 5?C8, OM 40 mg); placebo + OM (weeks 1?C2, placebo; weeks 3?C4, OM 20 mg; weeks 5?C8, OM 40 mg); and LOS (weeks 1?C4, LOS 50 mg; weeks 5?C8, LOS 100 mg). Analyses focused on comparison of OM and placebo + OM combined versus LOS. Efficacy endpoints were mean change from baseline in seated cuff diastolic blood pressure (SeDBP) at week 8 (primary); seated cuff systolic blood pressure (SeSBP) at weeks 4 and 8, and SeDBP at week 4 (secondary), and BP target achievement (tertiary).

Results

The randomized population (n = 941) had a mean ± SD age of 51.9 ± 9.7 years, 54.5% were male, and 20.1% were na?ve to antihypertensive medication. For treatmentna?ve subjects, baseline seated BP (SeBP) (±SD) was 157.4 (±10.9)/101.8 (±4.3) mmHg with OM and 156.3 (±10.8)/101.1 (±3.9) mmHg with LOS, while non-na?ve subjects had 158.4 (±10.2)/100.9 (±4.0) mmHg with OM and 158.8 (±10.1)/101.3 (±4.2) mmHg with LOS. OM monotherapy produced significantly greater changes in least-squares mean (±SE) SeDBP compared with LOS in both treatment-na?ve (?9.7 [1.0] vs. ?6.6 [1.0] mmHg; P = 0.0232 vs. LOS) and non-na?ve subjects (?9.6 [0.5] vs. ?7.3 [0.5] mmHg; P = 0.0013 vs. LOS). A significantly greater proportion of patients achieved the SeBP goal of <140/90 mmHg with OM compared with LOS in treatment-na?ve (34.1% vs. 19.0%, respectively; P = 0.0109) and non-na?ve subjects (31.0% vs. 19.6%; P = 0.0008).

Conclusion

Overall, OM monotherapy resulted in significantly greater SeBP reductions and greater SeBP goal achievement than LOS, irrespective of previous medication use. Both OM and LOS therapy were well tolerated.     

Evaluation of the Efficacy and Safety of a Hydrochlorothiazide to Chlorthalidone Medication Change in Veterans With Hypertension

Background

There are few data available examining the clinical impact of switching patients from hydrochlorothiazide (HCTZ) to chlorthalidone for blood pressure management.

Objectives

The goal of this study was to compare within-patient clinic blood pressure readings, serum electrolyte levels, and renal function markers before and after a medication change from HCTZ to chlorthalidone in a veteran population.

Methods

This was a retrospective, pre- and postmeasure, self-controlled study. Veterans Affairs Ann Arbor Healthcare System patients switched from HCTZ to chlorthalidone between January 1, 2001, and January 31, 2012, who had at least 1 follow-up clinic blood pressure reading recorded between 2 and 8 weeks from the date of the medication change were included in the study. Mean pre- and postmeasure values for systolic and diastolic clinic blood pressures, serum potassium, serum sodium, serum calcium, serum creatinine, and blood urea nitrogen were compared by using a 2-tailed, paired t test with a significance level (α) of 0.05.

Results

Of the 40 patients included in the study 95% were male, 65% were white, and the mean age was 64.9 (10.8) years. Both mean systolic (–15.8 mm Hg [95% CI, 8.9 to 22.6], P < 0.0001) and mean diastolic (–4.2 mm Hg [95% CI, 1.5 to 6.9], P = 0.0035) blood pressures showed statistically and clinically significant reductions after the medication change. A statistically significant decrease in mean sodium (–1.1 mmol/L [95% CI, 0.4 to 1.9], P = 0.003) and an increase in mean serum creatinine (0.06 mg/dL [95% CI, –0.09 to –0.02], P = 0.002) was observed; however, these changes may not be viewed as clinically significant by many practitioners. No statistically significant changes were observed in any of the other outcomes examined. Most patients (38 of 40) were taking at least 1 additional antihypertensive agent; 73% of patients were using ≥3 antihypertensive agents at the time of the medication change.

Conclusions

In patients with hypertension already taking HCTZ, switching to chlorthalidone seems to further reduce systolic and diastolic blood pressures without any clinically significant changes in renal function or electrolyte levels.     

Dietary salt intake and mortality in patients with type 2 diabetes

OBJECTIVE

Many guidelines recommend that patients with type 2 diabetes should aim to reduce their intake of salt. However, the precise relationship between dietary salt intake and mortality in patients with type 2 diabetes has not been previously explored.

RESEARCH DESIGN AND METHODS

Six hundred and thirty-eight patients attending a single diabetes clinic were followed in a prospective cohort study. Baseline sodium excretion was estimated from 24-h urinary collections (24hU_Na). The predictors of all-cause and cardiovascular mortality were determined by Cox regression and competing risk modeling, respectively.

RESULTS

The mean baseline 24hU_Na was 184 ± 73 mmol/24 h, which remained consistent throughout the follow-up (intraindividual coefficient of variation [CV] 23 ± 11%). Over a median of 9.9 years, there were 175 deaths, 75 (43%) of which were secondary to cardiovascular events. All-cause mortality was inversely associated with 24hU_Na, after adjusting for other baseline risk factors (P < 0.001). For every 100 mmol rise in 24hU_Na, all-cause mortality was 28% lower (95% CI 6–45%, P = 0.02). After adjusting for the competing risk of noncardiovascular death and other predictors, 24hU_Na was also significantly associated with cardiovascular mortality (sub-hazard ratio 0.65 [95% CI 0.44–0.95]; P = 0.03).

CONCLUSIONS

In patients with type 2 diabetes, lower 24-h urinary sodium excretion was paradoxically associated with increased all-cause and cardiovascular mortality. Interventional studies are necessary to determine if dietary salt has a causative role in determining adverse outcomes in patients with type 2 diabetes and the appropriateness of guidelines advocating salt restriction in this setting.In patients with type 2 diabetes, hypertension is associated with a range of adverse outcomes including cardiovascular disease (CVD) and premature mortality. Consequently, clinical guidelines recommend that patients with type 2 diabetes undertake measures to maintain a blood pressure at or below target levels. Among the interventions advocated to assist in achieving these targets, most guidelines recommend a reduced intake of salt, as dietary sodium intake is positively correlated with blood pressure levels in the general population (1). Moreover, in patients with type 2 diabetes, salt restriction confers a modest reduction in blood pressure (2), and salt supplementation reduces the antihypertensive efficacy of blood pressure–lowering agents in the short term (3). However, the precise relationship between salt intake and mortality in patients with type 2 diabetes has not been previously explored. It is widely assumed that any blood pressure lowering associated with reduced dietary salt intake may be translated into protection from end-organ damage in the context of diabetes. However, there is also evidence that reduced sodium intake is associated with activation of metabolic and neurohormonal pathways, including the sympathetic nervous system (4) and the renin-angiotensin-aldosterone system (RAAS) (4), as well as increases in total and LDL cholesterol (4) and reduced peripheral insulin sensitivity (5). In the context of type 2 diabetes, each of these factors may offset or even outweigh gains achieved from blood pressure lowering. Hence, in this study we explored the association between dietary salt intake, the best estimate of which is 24-h urine collection as ∼90% of dietary sodium intake is renally excreted (6), and all-cause and cardiovascular mortality in patients with type 2 diabetes.     

Impaired aortic distensibility and elevated central blood pressure in Turner Syndrome: a cardiovascular magnetic resonance study

Background

Women with Turner Syndrome have an increased risk for aortic dissection. Arterial stiffening is a risk factor for aortic dilatation and dissection. Here we investigate if arterial stiffening can be observed in Turner Syndrome patients and is an initial step in the development of aortic dilatation and subsequent dissection.

Methods

Fifty-seven women with Turner Syndrome (48 years [29–66]) and thirty-six age- and sex-matched controls (49 years [26–68]) were included. Distensibility, blood pressure, carotid-femoral pulse wave velocity (PWV), the augmentation index (Aix) and central blood pressure were determined using cardiovascular magnetic resonance, a 24-h blood pressure measurement and applanation tonometry. Aortic distensibility was determined at three locations: ascending aorta, transverse aortic arch, and descending aorta.

Results

Mean aortic distensibility in the descending aorta was significantly lower in Turner Syndrome compared to healthy controls (P =?0.02), however, this was due to a much lower distensibility among Turner Syndrome with coarctation, while Turner Syndrome without coarctation had similar distensibility as controls. Both the mean heart rate adjusted Aix (31.4% vs. 24.4%; P?=?0.02) and central diastolic blood pressure (78.8 mmHg vs. 73.7 mmHg; P?=?0.02) were higher in Turner Syndrome compared to controls, and these indices correlated significantly with ambulatory night-time diastolic blood pressure. The presence of aortic coarctation (r = ??0.44, P =?0.005) and a higher central systolic blood pressure (r = ??0.34, P =?0.03), age and presence of diabetes were inversely correlated with aortic distensibility in TS.

Conclusion

Aortic wall function in the descending aorta is impaired in Turner Syndrome with lower distensibility among those with coarctation of the aorta, and among all Turner Syndrome higher Aix, and elevated central diastolic blood pressure when compared to sex- and age-matched controls.

Trial registration

The study was registered at ClinicalTrials.gov (#NCT01678274) on September 3, 2012.

     

Factors associated with undiagnosed obstructive sleep apnoea in hypertensive primary care patients

Objective

In hypertensive primary care patients below 65 years of age, (i) to describe the occurrence of undiagnosed obstructive sleep apnoea (OSA), and (ii) to identify the determinants of moderate/severe OSA.

Design

Cross-sectional.

Setting

Four primary care health centres in Sweden.

Patients

411 consecutive patients (52% women), mean age 57.9 years (SD 5.9 years), with diagnosed and treated hypertension (BP >140/90).

Main outcome measures

Occurrence of OSA as measured by the apnoea hypopnoea index (AHI).

Results

Mild (AHI 5–14.9/h) and moderate/severe (AHI > 15/h) OSA were seen among 29% and 30% of the patients, respectively. Comparing those without OSA with those with mild or moderate/severe OSA, no differences were found in blood pressure, pharmacological treatment (anti-hypertensive, anti-depressive, and hypnotics), sleep, insomnia symptoms, daytime sleepiness, or depressive symptoms. Obesity (BMI > 30 kg/m2) was seen in 30% and 68% of the patients with mild and moderate/severe OSA, respectively. Male gender, BMI > 30 kg/m2, snoring, witnessed apnoeas, and sleep duration >8 hours were determinants of obstructive sleep apnoea.

Conclusion

Previously undiagnosed OSA is common among patients with hypertension in primary care. Obesity, snoring, witnessed apnoeas, long sleep duration, and male gender were the best predictors of OSA, even in the absence of daytime sleepiness and depressive symptoms.Key Words: Depression, hypertension, obstructive sleep apnoea, sleep, sleep disordered breathing, snoringCurrent awareness:

• Obstructive sleep apnoea has been linked to hypertension in sleep clinic populations, but there is a lack of knowledge regarding the occurrence in Swedish hypertensive primary care patients.

Main statements:

• Undiagnosed mild and moderate/severe obstructive sleep apnoea was seen among 29% and 30% of patients, respectively.
• Comparing subjects with mild or moderate/severe obstructive sleep apnoea with those without, no differences were found in blood pressure, self-rated sleep duration, insomnia, daytime sleepiness, or depressive symptoms.
• Male gender, BMI > 30 kg/m00B2, snoring, witnessed apnoeas, and sleep duration >8 hours were determinants of moderate/severe obstructive sleep apnoea in hypertensive primary care patients.

     

Blood Pressure Control with Angiotensin Receptor Blocker-Based Three-Drug Combinations: Key Trials

Introduction

Most hypertensive patients only achieve blood pressure (BP) control with a combination of antihypertensive drugs from different classes and many require three or more drugs. Two three-drug, fixed-dose combinations are available: (1) the angiotensin receptor blocker (ARB), valsartan (VAL), the calcium channel blocker, amlodipine (AML), and the diuretic, hydrochlorothiazide (HCTZ); (2) the ARB, olmesartan medoxomil (OLM), AML, and HCTZ.

Methods

This article reviews two clinical studies in patients with moderate-to-severe hypertension, which compared the efficacy and safety of VAL/AML/HCTZ and OLM/AML/HCTZ with the component two-drug combinations.

Results

Each triple combination produced significantly greater reductions in seated systolic/diastolic BP and higher BP control rates than the two-drug combinations. Subgroup analyses showed that BP reductions and control rates with the three-drug combinations were unaffected by age, gender, race, and hypertension severity (VAL/AML/HCTZ and OLM/AML/HCTZ), and that efficacy was maintained for up to 52 weeks (OLM/AML/HCTZ). OLM/AML/HCTZ and VAL/AML/HCTZ also produced significantly larger reductions in ambulatory systolic and diastolic BP over 24 hours, the daytime, and nighttime compared with two-drug combinations. Adverse events were mainly of mild or moderate intensity and each threedrug combination was well tolerated.

Conclusion

ARB/AML/HCTZ combinations produce BP reductions and control rates superior to two-drug combinations and may help difficult-to-treat patients to achieve BP control.     

Effectiveness of a Fixed-Dose,Single-Pill Combination of Perindopril and Amlodipine in Patients with Hypertension: A Non-Interventional Study

Introduction

We conducted a prospective, non-interventional, multicenter study to examine the effect of a fixed-dose combination of perindopril/amlodipine in patients with arterial hypertension.

Methods

Patients who were previously untreated or required a change in medication were treated with a fixed combination of perindopril/amlodipine (3.5/2.5 or 7.0/5.0 mg) for 12 weeks. Changes in office, home and ambulatory blood pressure (BP) were recorded. Adherence was assessed by the Hill-Bone medication adherence scale.

Results

Overall, 1814 patients (mean age 60.0 ± 13.4 years) were included in 614 German practices, and data of 1770 patients were analyzed. At study entry, 97.7% of patients received perindopril/amlodipine at a daily dose of 3.5 mg/2.5 mg, and 47.9% of patients remained on this dose during the study period. Treatment with perindopril/amlodipine decreased mean office BP from 163.7/95.4 to 133.6/80.3 mmHg (p < 0.0001), resulting in a hypertension control rate of 69.1%. Blood pressure control was comparable in previously untreated and treated patients (70.3 vs. 68.1%), and in younger and older patients (70.6 < 65 vs. 66.3% ≥ 65 years). Ambulatory BP measurements were available in a subgroup of patients (n = 167), and mean 24 h ambulatory BP decreased from 150.6 ± 12.6/88.9 ± 8.8 to 132.4 ± 11.9/79.4 ± 8.5 mmHg (p < 0.0001). Furthermore, the proportion of patients with severe hypertension European Society of Hypertension/European Society of Cardiology (ESH/ESC) grade II or III decreased from 64.4 to 3.9%, and patients with pre-existing isolated systolic hypertension (n = 284) converted to normal BP in 67.6% of cases. Nearly half of the patients (47.2%) were perfectly adherent during the study. In previously treated patients, the percentage of patients with perfect adherence increased from 20.6% prior to study to 43.5% at final visit (p < 0.0001). Adverse drug reactions were documented for 4.9% of patients.

Conclusion

A fixed-dose combination of perindopril/amlodipine shows significant blood pressure reduction and improvement in medication adherence in a primary care setting.

Trial Registration

ISRCTN26323538.

Funding

Servier Deutschland GmbH.

     

Does mad honey poisoning require hospital admission?

Background

The aim of this study was to describe current patterns of monitoring and treatment of mad honey intoxication to make recommendations for a more standardized approach to care of patients with mad honey poisoning.

Methods

Patients presenting to emergency departments because of honey poisoning between January and October 2007. Age, length of stay in the emergency department, pulse rate, and systolic and diastolic blood pressure are cited as mean ± SD.

Results

Forty-seven cases presenting to the 3 health institutions during 2007 were investigated. It was determined that patients had ingested “mad” honey between 0.5 and 9 hours (mean ± SD, 2.8 ± 1.8 hours) before presentation. Patients' pulse rates were 30 to 77/min (mean ± SD, 46.6 ± 12.1/min), and systolic blood pressure ranged from 50 to 140 mm Hg (mean ± SD, 46.6 ± 12.1 mm Hg). Patient rhythms on arrival were determined as 37 (7.7%) sinus bradycardia, 6 (12.8%) nodal rhythm, 3 (6.4%) normal sinus rhythm, and 1 (2.1%) complete atrioventricular block. Lengths of stay in hospital were 3.6 ± 2.2 hours in the first university hospital, 22.2 ± 3.8 hours in the second university hospital, and 3.4 ± 1.7 hours in the state hospital. A 0.5 to 2 mg of atropine was given to all patients.

Conclusions

Our study did not reveal any difference in complications or mortality between patients cared for with brief emergency department observation when compared with patients cared for with 1 day inpatient observation.     

Comparison between dexmedetomidine and midazolam for sedation of eclampsia patients in the intensive care unit

Purpose

This study compares the effectiveness of midazolam and dexmedetomidine for the sedation of eclampsia patients admitted to our intensive care unit (ICU).

Patients and Methods

Forty women with eclampsia requiring termination of pregnancy by caesarean delivery were randomized in to 2 groups of 20 to receive either midazolam or dexmedetomidine. The midazolam group received a loading dose of 0.05 mg/kg followed by an infusion of 0.1 mg kg⁻¹ h⁻¹. The dexmedetomidine group loading dose was 1 μg/kg per 20 minutes, followed by continuous infusion at 0.7 μg kg⁻¹ h⁻¹. Heart rate, blood pressure, Ramsey sedation score, antihypertensive need, convulsion fits, and duration in ICU were monitored and recorded all through the ICU stay.

Results

Dexmedetomidine markedly reduced heart rates for the first 24 hours (P < .05) compared with midazolam, but there were no differences at 48 and 72 hours. Mean arterial blood pressures were similar in the 2 groups (P > .05), although in the dexmedetomidine group, it was lower at 5, 6, 12, and 24 hours compared with the first 4 hours (P < .05). Moreover, fewer patients given dexmedetomidine required nitroglycerine and nitroprusside (P < .05). The duration of ICU stay was less in the dexmedetomidine group, 45.5 hours (range, 15-118 hours), than in the midazolam group, 83 hours (minimum-maximum, 15-312 hours).

Conclusion

Dexmedetomidine sedation in eclampsia patients is effective in reducing the demand for antihypertensive medicine and duration of ICU stay.     

The effect of clinically relevant pressure duration on sacral skin blood flow and temperature in patients after acute spinal cord injury

Sae-Sia W, Wipke-Tevis DD, Williams DA. The effect of clinically relevant pressure duration on sacral skin blood flow and temperature in patients after acute spinal cord injury.

Objective

To test the effect of clinically relevant duration of pressure loading (2h) on sacral skin blood flow (SBF) and skin temperature in subjects with spinal cord injury (SCI) within 24 to 96 hours after injury compared with subjects with acute orthopedic trauma and healthy subjects.

Design

Three-group, repeated-measures, inception cohort.

Setting

Three acute care hospitals in southern Thailand.

Participants

Convenience sample of 20 subjects with acute SCI within 24 to 96 hours after injury. Age- and sex-matched subjects with acute orthopedic trauma (n=35) and healthy subjects (n=47) served as comparison groups.

Interventions

Not applicable.

Main Outcome Measures

Sacral SBF and skin temperature were measured simultaneously by using a laser Doppler sensor and thermocouple sensor, respectively, with subjects lying in the lateral (baseline, no pressure, 30min), supine (pressure loading, 2h), and lateral position (recovery, no pressure, 90min).

Results

Baseline skin temperature was higher in subjects with acute SCI (P<.05) compared with subjects with orthopedic trauma and healthy subjects. A relative decrease in sacral SBF occurred in subjects with acute SCI (P<.01) over 2 hours of pressure loading compared with subjects with orthopedic trauma and healthy subjects. During the same time course, subjects with acute SCI had a smaller increase in sacral skin temperature compared with subjects with orthopedic trauma and healthy subjects (P<.001). During recovery, the time to the initial sacral SBF-reactive hyperemia response was shorter in subjects with acute SCI compared with subjects with orthopedic trauma (P<.001) and healthy subjects (P=.003). Additionally, the initial positive slope of the SBF reactive hyperemia response was higher in subjects with acute SCI than subjects with orthopedic trauma (P=.005) and healthy (P=.004) subjects.

Conclusions

Collectively, a negative change in SBF during pressure loading plus a shorter time to increase and greater slope for SBF after pressure release reveal microvascular dysfunction in acute SCI subjects. The clinical relevance of the protocol suggests that turning interval guidelines may require reevaluation for patients with acute SCI.