Effectiveness of dietary inorganic nitrate for lowering blood pressure in hypertensive adults: a systematic review.

OBJECTIVE: The objective of this review was to evaluate the effectiveness of inorganic nitrate on blood pressure in hypertensive adults. INTRODUCTION: Hypertension is associated with increased risk of morbidity and mortality in adults. Inorganic nitrate could be beneficial for lowering blood pressure and reducing cardiovascular disease risks. Evidence related to the treatment of hypertension through sources of inorganic nitrate has been presented. INCLUSION CRITERIA: The review considered studies on adults aged 18 years and over, with blood pressure greater than 120/80 mmHg, undergoing interventions focusing on the effects of inorganic nitrate on blood pressure. Studies that included inorganic nitrate intake via dietary modification, in the form of a dietary supplement, and/or by the consumption of beetroot juice were considered. The comparator was no intervention of inorganic nitrate; different dosage, frequency, duration of inorganic nitrate; and other interventions that are administered to reduce and manage blood pressure. The primary outcomes were systolic and diastolic blood pressure effects. Experimental, quasi-experimental, analytical observational and pilot study designs were considered for inclusion. METHODS: Databases were searched for published and unpublished studies, available in English, from January 2013 to January 2018. Critical appraisal was conducted using standardized instruments from the Joanna Briggs Institute (JBI) and the methodological quality of included studies was considered to be moderate. Data were extracted using the JBI data extraction instrument. Data were presented in a narrative form due to the heterogeneity of included studies. RESULTS: Twelve papers were included in the systematic review with a total of 321 participants. Ten were randomized controlled trials and two were quasi-experimental studies. All participants had baseline blood pressures greater than 120/80 mmHg. Some studies included participants with comorbidities such as diabetes or heart failure with preserved ejection fraction. Inorganic nitrate was administered multiple ways throughout the studies including the following: beetroot juice, beetroot gel, nitric oxide lozenge, high nitrate diet, and raw and cooked beet juice. Doses and treatment intervals varied. Some studies included exercise as part of the intervention protocol.Meta-analysis was not conducted due to heterogeneity that existed within the studies. Blood pressure was measured in multiple settings by manual, digital or ambulatory means. The noted outcome patterns were as follows: no change in systolic blood pressure and diastolic blood pressure, decrease in systolic blood pressure and diastolic blood pressure, or decrease in systolic blood pressure with no change in diastolic blood pressure. Possible reasons for the diverse findings include the following: age, comorbidities, use of antihypertensives by participants; source and dose of nitrate; and intervention and follow-up time frames. CONCLUSIONS: There is insufficient evidence to support or refute the use of inorganic nitrate for any effect on blood pressure at this time. Therefore, there is no concrete base for the development of practice guidelines until stronger evidence becomes available. The gaps in the literature along with the study limitations identified necessitate the need for more research on inorganic nitrate and how it relates to blood pressure.

Quality of integrated chronic disease care in rural South Africa: user and provider perspectives.

The integrated chronic disease management (ICDM) model was introduced as a response to the dual burden of HIV/AIDS and non-communicable diseases (NCDs) in South Africa, one of the first of such efforts by an African Ministry of Health. The aim of the ICDM model is to leverage HIV programme innovations to improve the quality of chronic disease care. There is a dearth of literature on the perspectives of healthcare providers and users on the quality of care in the novel ICDM model. This paper describes the viewpoints of operational managers and patients regarding quality of care in the ICDM model. In 2013, we conducted a case study of the seven PHC facilities in the rural Agincourt sub-district in northeast South Africa. Focus group discussions (n = 8) were used to obtain data from 56 purposively selected patients ≥18 years. In-depth interviews were conducted with operational managers of each facility and the sub-district health manager. Donabedian's structure, process and outcome theory for service quality evaluation underpinned the conceptual framework in this study. Qualitative data were analysed, with MAXQDA 2 software, to identify 17 a priori dimensions of care and unanticipated themes that emerged during the analysis. The manager and patient narratives showed the inadequacies in structure (malfunctioning blood pressure machines and staff shortage); process (irregular prepacking of drugs); and outcome (long waiting times). There was discordance between managers and patients regarding reasons for long patient waiting time which managers attributed to staff shortage and missed appointments, while patients ascribed it to late arrival of managers to the clinics. Patients reported anti-hypertension drug stock-outs (structure); sub-optimal defaulter-tracing (process); rigid clinic appointment system (process). Emerging themes showed that patients reported HIV stigmatisation in the community due to defaulter-tracing activities of home-based carers, while managers reported treatment of chronic diseases by traditional healers and reduced facility-related HIV stigma because HIV and NCD patients attended the same clinic. Leveraging elements of HIV programmes for NCDs, specifically hypertension management, is yet to be achieved in the study setting in part because of malfunctioning blood pressure machines and anti-hypertension drug stock-outs. This has implications for the nationwide scale up of the ICDM model in South Africa and planning of an integrated chronic disease care in other low- and middle-income countries.

A modified device for continuous non-invasive blood pressure measurements in humans under hyperbaric and/or oxygen-enriched conditions.

BACKGROUND: It would be desirable to safely and continuously measure blood pressure noninvasively under hyperbaric and/or hyperoxic conditions, in order to explore haemodynamic responses in humans under these conditions. METHODS: A systematic analysis according to 'failure mode and effects analysis' principles of a commercially available beat-by-beat non-invasive blood pressure monitoring device was performed using specifications provided by the manufacturer. Possible failure modes related to pressure resistance and fire hazard in hyperbaric and oxygen-enriched environments were identified and the device modified accordingly to mitigate these risks. The modified device was compared to an unaltered device in five healthy volunteers under normobaric conditions. Measurements were then performed under hyperbaric conditions (243 kPa) in five healthy subjects. RESULTS: Modifications required included: 1) replacement of the carbon brush motorized pump by pressurized air connected through a balanced pressure valve; 2) modification of the 12V power supply connection in the multiplace hyperbaric chamber, and 3) replacement of gas-filled electrolytic capacitors by solid equivalents. There was concurrence between measurements under normobaric conditions, with no significant differences in blood pressure. Measurements under pressure were achieved without problems and matched intermittent measurement of brachial arterial pressure. CONCLUSION: The modified system provides safe, stable, continuous non-invasive blood pressure trends under both normobaric and hyperbaric conditions.

Telemedicine and M-Health in Hypertension Management: Technologies, Applications and Clinical Evidence.

Electronic processes and communication technologies are more and more often employed to provide healthcare services to caregivers and their patients. Such solutions are currently referred as e-health, the most popular and widely distributed being those based on telemedicine and mobile health (m-health). A specific application of telemedicine for hypertension management is blood pressure telemonitoring (BPT), which allows remote data transmission of BP and additional information on patients' health status from their living site or from a community setting to the doctor's office or the hospital. Several randomized studies have documented a significant BP reduction with regular BPT compared to usual care, particularly in high risk hypertensive patients. Additional benefits are observed when BPT is offered under the supervision of a team of healthcare professionals, including a community pharmacist. BPT may also be provided in the context of m-health solutions, which commonly include wireless diagnostic and clinical decision support tools. M-health has the potential to promote patient's self-management, as a complement to the doctor's intervention, and encourage greater participation in medical decision making. Current statistics show that half of smartphone owners gather health information through their phone and 19 % use a health app. In case of hypertensive patients the most popular apps are those with tracking function, including BPT. Thus, e-health, and in particular BPT and m-health, are progressively gaining a key role in the management of hypertensive patients, having the potential to improve the quality of the delivered care and to more effectively prevent cardiovascular consequences of high BP.

Effects of aerobic dance training on blood pressure in individuals with uncontrolled hypertension on two antihypertensive drugs: a randomized clinical trial.

There is a dearth of reports on possible additive blood pressure (BP)-reducing effect of aerobic exercise on antihypertensive drug in humans. This study investigated the additive BP-reducing effect of aerobic exercise on BP in individuals with uncontrolled hypertension. In this 12-week double-blind study, 120 new-diagnosed individuals with mild-to-moderate hypertension were randomized to receive coamilozide + 5/10 mg of amlodipine + aerobic dance or coamilozide + 5/10 mg of amlodipine alone. Forty-five and 43 participants in exercise and control groups, respectively, completed the 12-week intervention. Addition of aerobic exercise to antihypertensive drug therapy significantly reduced systolic BP (7.1 mm Hg [95% confidence interval: 5.0, 9.3]; P < .001) and diastolic BP (1.7 mm Hg [95% confidence interval: 0.4, 3.0]; P = .009) at 12 weeks. BP control rate differed significantly between exercise (53.9%) and control (35.3%) groups, P < .001. Postintervention, proportion of participants in exercise group who had their number of antihypertensive drug reduced to one (20.3%) differed from that in control group (11.1%); (χ(2) = 11.0; P = .001). Combination of aerobic dance and antihypertensive drugs reduces number of antihypertensive drugs needed to achieve BP control and enhances BP control in individuals with hypertension on two antihypertensive drugs.

Goal-Directed Fluid Therapy Guided by Cardiac Monitoring During High-Risk Abdominal Surgery in Adult Patients: Cost-Effectiveness Analysis of Esophageal Doppler and Arterial Pulse Pressure Waveform Analysis.

BACKGROUND: Several minimally invasive techniques for cardiac output monitoring such as the esophageal Doppler (ED) and arterial pulse pressure waveform analysis (APPWA) have been shown to improve surgical outcomes compared with conventional clinical assessment (CCA). OBJECTIVE: To evaluate the cost-effectiveness of these techniques in high-risk abdominal surgery from the perspective of the French public health insurance fund. METHODS: An analytical decision model was constructed to compare the cost-effectiveness of ED, APPWA, and CCA. Effectiveness data were defined from meta-analyses of randomized clinical trials. The clinical end points were avoidance of hospital mortality and avoidance of major complications. Hospital costs were estimated by the cost of corresponding diagnosis-related groups. RESULTS: Both goal-directed therapy strategies evaluated were more effective and less costly than CCA. Perioperative mortality and the rate of major complications were reduced by the use of ED and APPWA. Cost reduction was mainly due to the decrease in the rate of major complications. APPWA was dominant compared with ED in 71.6% and 27.6% and dominated in 23.8% and 20.8% of the cases when the end point considered was "major complications avoided" and "death avoided," respectively. Regarding cost per death avoided, APPWA was more likely to be cost-effective than ED in a wide range of willingness to pay. CONCLUSIONS: Cardiac output monitoring during high-risk abdominal surgery is cost-effective and is associated with a reduced rate of hospital mortality and major complications, whatever the device used. The two devices evaluated had negligible costs compared with the observed reduction in hospital costs. Our comparative studies suggest a larger effect with APPWA that needs to be confirmed by further studies.

Closed-loop control of renal perfusion pressure in physiological experiments.

This paper presents the design, experimental modeling, and control of a pump-driven renal perfusion pressure (RPP)-regulatory system to implement precise and relatively fast RPP regulation in rats. The mechatronic system is a simple, low-cost, and reliable device to automate the RPP regulation process based on flow-mediated occlusion. Hence, the regulated signal is the RPP measured in the left femoral artery of the rat, and the manipulated variable is the voltage applied to a dc motor that controls the occlusion of the aorta. The control system is implemented in a PC through the LabView software, and a data acquisition board NI USB-6210. A simple first-order linear system is proposed to approximate the dynamics in the experiment. The parameters of the model are chosen to minimize the error between the predicted and experimental output averaged from eight input/output datasets at different RPP operating conditions. A closed-loop servocontrol system based on a pole-placement PD controller plus dead-zone compensation was proposed for this purpose. First, the feedback structure was validated in simulation by considering parameter uncertainty, and constant and time-varying references. Several experimental tests were also conducted to validate in real time the closed-loop performance for stepwise and fast switching references, and the results show the effectiveness of the proposed automatic system to regulate the RPP in the rat, in a precise, accurate (mean error less than 2 mmHg) and relatively fast mode (10-15 s of response time).

Beyond conventional considerations: newer devices used in blood pressure measurement and management.

Several noninvasive devices are now available to assess blood vessel structure and function and have been shown in longitudinal cohort studies to provide additional cardiovascular event prediction over that obtained by conventional brachial blood pressure (BP) measurements. Among these newer measurements are estimates of vascular stiffness (as determined by the pulse wave velocity in the aorta) and measures of pulse wave reflection. Pulse wave velocity, in particular, has been well studied in end-stage kidney (ESKD) populations where it predicts cardiovascular events and death independently of standard BP. In addition, there are minimum 3 devices, either marketed or used in clinical trials, that are useful in some clinical situations as an adjunct to drug therapy for managing high BP. This review will focus on the roles of these new technologies in evaluating and managing high BP, emphasizing the CKD/ESKD patient where possible, although data are limited in the kidney disease population when it comes to managing BP with these novel device approaches.

Implementation of MP3 player for music therapy on hypertension.

Hypertension is a common clinical disease and a major risk to human health. Many clinical findings indicate that certain types of music can reduce blood pressure (BP), and music therapy is considered as an important part of anti-hypertension treatment. We integrate our former related research achievement into the new MP3 player, which can also detect the current BP value with a cuffless measurement method. According to the current BP value, the MP3 player selects certain types of music for playing in order to alleviate the hypertension of patients.

[The value of complior method for studying the endothelial dysfunction in hypertensive patients]. / Valoarea metodei complior in studiul disfunctiei endoteliale la pacientii hipertensivi.

OBJECTIVE: Non-invasive methods that measure the arterial stiffness and wave reflection have recently been used for assessing the endothelial dysfunction. Despite this fact, Complior method, which can study the relation between nitric oxide (NO) and pulse wave velocity as a measure of arterial stiffness, is not currently used. Our study evaluates the potential of Complior technique for a global assessing of the endothelial dysfunction. MATERIAL AND METHODS: Endothelial dysfunction was prospectively studied before and after 6 and 12 months of antihypertensive treatment in 92 hypertensive patients, strictly selected and 50 matched normotensives. The studied parameters were pulse wave velocity (PWV) and its variation under pharmacodynamic stimulation. NO-dependent/ independent vasodilatation were assessed with 400 microg Ventolin spray (deltaPWV% = BR) and 0.5 mg sublingual NTG (deltaPWV% = NR1), respectively. RESULTS: 1. The endothelial dysfunction has a large interindividual variability, irrespective the blood pressure values. 2. The endothelial dysfunction is a heterogenous condition, being more affected in peripheral arterial territory and in NO-dependent component. 3. Therapeutic effect depends on vascular structure and antihypertensive regimen. ACE inhibitors and calcium channel blockers have complementary intervention, so the combination can be useful for a better therapeutic control of the endothelial dysfunction. CONCLUSION: Complior is a very useful method for studying the complex profile of endothelial dysfunction and can complete the vascular ultrasound data for peripheral arterial site.

A cardiovascular monitoring system in conscious cynomolgus monkeys for regulatory safety pharmacology. Part 1: Non-pharmacological validation.

INTRODUCTION: This project addresses the validation study design of a test system using a telemetered non-human primate model for cardiovascular safety pharmacology evaluation. METHODS: The validation provided by the supplier evaluated installation (IQ) and operation (OQ) qualifications. This protocol was completed with tests evaluating electronic data management and accuracy and precision of transmitter (n=4) measurements for temperature and pressure criteria with a series of tested values. As part of performance qualification, physical activity (for 24 h) as well as cardiovascular, ECG (20 complexes for each animal) and systemic arterial blood pressure (SAP, 10 different measures), data were recorded simultaneously from the same animals (n=4) using certified equipment and the telemetry system. Reliability was evaluated over 60 days. RESULTS: The IQ and OQ were completed successfully. The electronic data management was performed successfully. The ex-vivo evaluation for temperature and pressure showed high correlation (R(2)>0.99) but with a slight pressure shift, as expected, with this transmitter model. For physical activity, the correlation coefficients were good to excellent with high activity counts but the comparison demonstrated a limited sensitivity of the telemetry system with animal presenting low activity levels. ECG interval measurement using the telemetry software was considered at least equivalent to manual measurement, but with some limitations in the reading of the ECG. The comparison between both methods of SAP measurement showed adequate precision (R(2)=0.969) but no accuracy. DISCUSSION: Reference monitoring methods are important to ensure proper test system validation. Monitoring with a reference methodology and the telemetry system is important in order to evaluate precision and accuracy of the test system. Computerized analysis may lack the capability to analyze ECG complexes with abnormal morphologies. This reinforces the need to have ECG evaluation prior to telemetry implantation along with visual evaluation of ECG tracing at standard speed (e.g. 50 mm/s) at all time points.

Validity of a new feedback method for the VEMP test.

CONCLUSIONS: We used a feedback method, based on a blood pressure manometer with inflatable cuff, to control the sternocleidomastoid muscle (SCM) contraction. To obtain comparable left-right VEMP responses, it is necessary (1) to determine which cuff pressures on both sides yield identical mean rectified voltage (MRV) values of the SCM contraction and (2) to apply these cuff pressures during the VEMP test. OBJECTIVE: To investigate the effect of the SCM muscle contraction variability on the VEMP variables when applying the feedback method. MATERIALS AND METHODS: Subjects pushed with their jaw against the hand-held inflated cuff to generate cuff pressures of subsequently 30, 40 and 50 mmHg during a MRV and VEMP measurement. RESULTS: When analyzing the relationship between the applied cuff pressures and the MRV values/VEMP amplitudes, we showed that (1) there was a linear relationship, (2) there was no side effect and (3) there was an interaction effect between 'side' and 'subject'. There was neither a side effect, nor an effect of the applied cuff pressure when considering the p13 latencies. As for the n23 values, there was no side effect but there was a significant difference when comparing the n23 latencies at cuff pressures of 30 vs 40 mmHg/50 mmHg.

Some pyridazinone and phthalazinone derivatives and their vasodilator activities.

In this study, 6-[(4-arylidene-2-phenyl-5-oxoimidazolin-1-yl)phenyl]-4,5-dihydro-3(2H)-pyridazinone and 4-[(4-arylidene-2-phenyl-5-oxoimidazolin-1-yl)phenyl]-1(2H)-phthalazinone derivatives were synthesized by reacting 6-(4-aminophenyl)-4,5-dihydro-3(2H)-pyridazinone or 4-(4-aminophenyl)-1(2H)-phthalazinone compound with different 4-arylidene-2-phenyl-5(4H)-oxazolone derivatives. The vasodilator activities of the compounds were examined both in vitro and in vivo. Some pyridazinone derivatives showed appreciable activity.

Modern approaches to blood pressure measurement.

BACKGROUND: Blood pressure (BP) is usually measured by conventional sphygmomanometry. Although apparently simple, this procedure is fraught with many potential sources of error. This review focuses on two alternative techniques of BP measurement: ambulatory monitoring and self measurement. REVIEW: BP values obtained by ambulatory monitoring or self measurement are characterised by high reproducibility, are not subject to digit preference or observer bias, and minimise the transient rise of the blood pressure in response to the surroundings of the clinic or the presence of the observer, the so called white coat effect. For ambulatory monitoring, the upper limits of systolic/diastolic normotension in adults include 130/80 mm Hg for the 24 hour BP and 135/85 and 120/70 mm Hg for the daytime BP and night time BP, respectively. For the the self measured BP these thresholds include 135/85 mm Hg. Automated BP measurement is most useful to identify patients with white coat hypertension. Whether or not white coat hypertension predisposes to sustained hypertension remains debated. However, outcome is better correlated with the ambulatory BP than with the conventional BP. In patients with white coat hypertension, antihypertensive drugs lower the BP in the clinic, but not the ambulatory BP, and also do not improve prognosis. Ambulatory BP monitoring is also better than conventional BP measurement in assessing the effects of treatment. Ambulatory BP monitoring is necessary to diagnose nocturnal hypertension and is especially indicated in patients with borderline hypertension, elderly patients, pregnant women, patients with treatment resistant hypertension, and also in patients with symptoms suggestive of hypotension. CONCLUSIONS: The newer techniques of BP measurement are now well established in clinical research, for diagnosis in clinical practice, and will increasingly make their appearance in occupational and environmental medicine.

Intracompartmental pressure during hyperthermic isolated limb perfusion for melanoma and sarcoma.

Side effects of isolated limb perfusion (ILP) include rhabdomyolysis, paresthesia, or nerve palsy. The increase in intracompartmental pressure during ILP is thought to be linked to neuro- and muscular toxicity, and fasciotomy is recommended for protection. In 24 patients, intracompartmental pressure was measured. A flexible 5 F probe was placed into the non-tumour-bearing compartment of the perfused limb. Interstitial fluid pressure was measured using a piezoresistant tip. Compartmental pressure values were continuously recorded during and after ILP. The drugs used were a combination of doxorubicin, cisplatinum and melphalan or rhTNF-alpha combined with melphalan. The median overall compartmental pressure prior to ILP was 13 mmHg (range: 11-21 mmHg); during the heat-up phase the median pressure rose to 28 mmHg. During therapeutic perfusion a further increase could be documented and the maximum pressure measured was 90 mmHg; the median of the pressure maxima of all patients was 34 mmHg. During wash-out, at the end of the perfusion, a clear reduction in compartment pressures could be observed and the median dropped to a value of 27 mmHg. In all patients a continuous decrease in compartmental pressure could be recorded, reaching the pre-ILP values by 48 h post-operatively. A dramatic increase in compartmental pressure during ILP can be observed by continuous monitoring. Because of our observation that during the wash-out phase elevated compartmental pressures return to normal, there is no general indication for a fasciotomy. However, for patients maintaining a peak compartmental pressure above a critical threshold of 35 to 40 mmHg fasciotomy may be indicated.

Diversity of blood pressure recording during pregnancy: implications for the hypertensive disorders.

OBJECTIVE: To determine the number and type of methods used to measure blood pressure (BP) in pregnant women. DESIGN: Questionnaires were distributed to obstetricians and midwives concerning: method of recording BP (arm used, subject position, Korotkoff sounds recorded); accuracy of recording BP (cuff size, sphygmomanometer calibration); and definitions of hypertension in pregnancy. PARTICIPANTS: Obstetricians (academic, staff and private) in Sydney; members of the New South Wales Midwives' Association. MAIN RESULTS: Responses were received from 85 obstetricians (55% of those surveyed) and 173 midwives (43%); the overall response rate was 46%. Almost 80% of respondents agreed that diastolic BP above 90 mmHg constituted hypertension during pregnancy but at least six different methods were used to obtain BP readings, with a potentially large variability in the BP so obtained. Forty-five per cent of obstetricians and 72% of midwives stated that they always used a large cuff when necessary. Few had had their sphygmomanometer calibrated within the previous two years. CONCLUSIONS: There is considerable variability in the way BP is recorded in pregnant women. Hypertension in pregnancy may therefore be over or under diagnosed according to the method employed and there is an urgent need for international consensus on how to measure BP accurately in pregnancy.

Modification of an automated vascular diagnostic system for hyperbaric use.

Modifications of an automated, noninvasive vascular diagnostic system (VASCULAB, MedaSonics, Inc.) for measuring blood pressure and plethysmographic blood flow responses to normobaric and hyperbaric oxygenation are described. The system consisted of a pump for inflating and deflating blood pressure cuffs and a microprocessor program controller (VSC21) with ultrasound Doppler, strain-gauge plethysmograph, and chart recorder. Inclusion of the VSC21 controller in the chamber was required for performance of procedures that could not be controlled from outside the chamber. All other components were outside the chamber. For fire prevention the VSC21 controller was nitrogen-purged in an acrylic case mounted on a mobile cart. Pressure-cuff tubes were attached via adapted fittings and connectors in the cart to connector ports in the controller's front panel. Electrical power cables and instrument signal wires were routed through chamber penetrations to an electrical power source and other VASCULAB components, respectively, outside the chamber. Initially, compression of the chamber to pressures in excess of 1.68 bar disabled the VSC21, requiring removal of its front membrane panel and ventilation of its pressure-sensitive keypad switches. This allowed automated assessment of blood pressure and calf blood flow at test pressures of 1.97 and 2.96 bar.