Factors influencing the effects of dietary nitrate supplementation on nitric oxide biomarkers and blood pressure

Ingestion of nitrate (NO3-) from natural sources can improve indices of cardiovascular health and exercise tolerance. The aim of this thesis was to determine the impact of dietary NO3- as a therapeutic aid when consumed amongst factors that might affect its efficacy such as antibacterial mouthwash, blood donation, different food forms and co-ingestion with alcoholic beverages. Young, healthy, normotensive individuals volunteered to participate in each experiment and undergo an array of physiological assessments. Chapter 4: Mouth rinsing with chlorhexidine and non-chlorhexidine mouthwash prior to consumption of concentrated NO3--rich beetroot juice (BR), over 6 days, blunted the rise in plasma nitrite concentration ([NO2-]) by 53 % and 29 % respectively, compared with control. Chlorhexidine mouthwash also elevated systolic (SBP) and mean arterial (MAP) blood pressure (BP) during treadmill walking. Chapter 5: Short-term BR ingestion lowered the oxygen (O2) cost of moderate-intensity exercise (by ~ 4 %), better preserved muscle oxygenation and attenuated the decline in incremental exercise tolerance (by 5 %) following whole blood donation. Chapter 6: An array of different NO3--rich vehicles, including BR, beetroot flapjack (BF), non-concentrated beetroot juice (BL) and beetroot crystals (BC), elevated salivary, plasma and urinary NO3- concentration ([NO3-]) and [NO2-] when compared with baseline and control, with the largest increases in plasma [NO2-] occurring in BF and BR. BR also reduced SBP (~5 mmHg) and MAP (~ 3-4 mmHg), and BF reduced diastolic BP (DBP; ~ 4 mmHg). Chapter 7: A high NO3- salad, accompanied by polyphenol-rich (NIT-RW) and -low (NIT-A) alcoholic beverages and a water control (NIT-CON) elevated salivary, plasma and urinary [NO3-] and [NO2-] compared with control (CON). SBP was reduced 2 h post consumption of NIT-RW (-4 mmHg), NIT-A (-3 mmHg) and NIT-CON (-2 mmHg) compared with CON. DBP and MAP were also lower in NIT-A, and more so in NIT-RW, compared with NIT-CON. Overall, the findings in this thesis demonstrate the efficacy of naturally derived NO3- on NO metabolites, BP and exercise tolerance. The potential for such benefits to arise may be maximised if antibacterial mouthwash is avoided during supplementation and if NO3- is consumed as BR, BF or as a green leafy salad with or without an alcoholic beverage. It may also be suggested that NO3- ingestion can offset decrements in exercise tolerance following blood donation

Accuracy of automated blood pressure measurements in the presence of atrial fibrillation: systematic review and meta-analysis

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordAtrial fibrillation (AF) affects ~3% of the general population and is twice as common with hypertension. Validation protocols for automated sphygmomanometers exclude people with AF, raising concerns over accuracy of hypertension diagnosis or management, using out-of-office blood pressure (BP) monitoring, in the presence of AF. Some devices include algorithms to detect AF; a feature open to misinterpretation as offering accurate BP measurement with AF. We undertook this review to explore accuracy of automated devices, with or without AF detection, for measuring BP. We searched Medline and Embase to October 2018 for studies comparing automated BP measurement devices to a standard mercury sphygmomanometer contemporaneously. Data were extracted by two reviewers. Mean BP differences between devices and mercury were calculated, where not reported and compared; meta-analyses were undertaken where possible. We included 13 studies reporting 14 devices. Mean systolic and diastolic BP differences from mercury ranged from −3.1 to + 6.1/−4.6 to +9.0 mmHg. Considerable heterogeneity existed between devices (I 2 : 80 to 90%). Devices with AF detection algorithms appeared no more accurate for BP measurement with AF than other devices. A previous review concluded that oscillometric devices are accurate for systolic but not diastolic BP measurement in AF. The present findings do not support that conclusion. Due to heterogeneity between devices, they should be evaluated on individual performance. We found no evidence that devices with AF detection measure BP more accurately in AF than other devices. More home or ambulatory automated BP monitors require validation in populations with AF.National Institute for Health Research (NIHR

Prevalence of postural hypotension in primary, community and institutional care: a systematic review and meta-analysis

This is the final version. Available from MDPI via the DOI in this record. The datasets used and/or analysed during the current study are available from the corresponding authors on reasonable request.Background: Postural hypotension (PH), the reduction in blood pressure when rising from sitting or lying 0to standing, is a risk factor for falls, cognitive decline and mortality. However, it is not often tested for in primary care. PH prevalence varies according to definition, population, care setting and measurement method. The aim of this study was to determine the prevalence of PH across different care settings and disease subgroups. Methods: Systematic review, meta-analyses and meta-regression. We searched Medline and Embase to October 2019 for studies based in primary, community or institutional care settings reporting PH prevalence. Data and study level demographics were extracted independently by two reviewers. Pooled estimates for mean PH prevalence were compared between care settings and disease subgroups using random effects meta-analyses. Predictors of PH were explored using meta-regression. Quality assessment was undertaken using an adapted Newcastle-Ottawa Scale. Results: One thousand eight hundred sixteen studies were identified; 61 contributed to analyses. Pooled prevalences for PH using the consensus definition were 17% (95% CI, 14–20%; I^2=99%) for 34 community cohorts, 19% (15–25%; I^2=98%) for 23 primary care cohorts and 31% (15–50%; I^2=0%) for 3 residential care or nursing homes cohorts (P=0.16 between groups). By condition, prevalences were 20% (16–23%; I^2=98%) with hypertension (20 cohorts), 21% (16–26%; I^2=92%) with diabetes (4 cohorts), 25% (18–33%; I^2=88%) with Parkinson’s disease (7 cohorts) and 29% (25–33%, I^2=0%) with dementia (3 cohorts), compared to 14% (12–17%, I^2=99%) without these conditions (P<0.01 between groups). Multivariable meta-regression modelling identified increasing age and diabetes as predictors of PH (P<0.01, P=0.13, respectively; R^2=36%). PH prevalence was not affected by blood pressure measurement device (P=0.65) or sitting or supine resting position (P=0.24), however, when the definition of PH did not fulfil the consensus description, but fell within its parameters, prevalence was underestimated (P=0.01) irrespective of study quality (P =0.04). Conclusions: PH prevalence in populations relevant to primary care is substantial and the definition of PH used is important. Our findings emphasise the importance of considering checking for PH, particularly in vulnerable populations, to enable interventions to manage it. These data should contribute to future guidelines relevant to the detection and treatment of PH

Dietary nitrate supplementation attenuates the reduction in exercise tolerance following blood donation

PublishedJournal ArticleThis is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.We tested the hypothesis that dietary nitrate (NO3-)-rich beetroot juice (BR) supplementation could partially offset deteriorations in O2 transport and utilization and exercise tolerance after blood donation. Twenty-two healthy volunteers performed moderate-intensity and ramp incremental cycle exercise tests prior to and following withdrawal of ~450 ml of whole blood. Before donation, all subjects consumed seven 70-ml shots of NO3--depleted BR [placebo (PL)] in the 48 h preceding the exercise tests. During the 48 h after blood donation, subjects consumed seven shots of BR (each containing 6.2 mmol of NO3-, n = 11) or PL (n. = 11) before repeating the exercise tests. Hemoglobin concentration and hematocrit were reduced by ~8-9% following blood donation (P < 0.05), with no difference between the BR and PL groups. Steady-state 02 uptake during moderate-intensity exercise was ~4% lower after than before donation in the BR group (P < 0.05) but was unchanged in the PL group. The ramp test peak power decreased from predonation (341 ± 70 and 331 ± 68 W in PL and BR, respectively) to postdonation (324 ± 69 and 322 ± 66 W in PL and BR, respectively) in both groups (P < 0.05). However, the decrement in performance was significantly less in the BR than PL group (2.7% vs. 5.0%, P < 0.05). NO3 supplementation reduced the 02 cost of moderate-inten-sity exercise and attenuated the decline in ramp incremental exercise performance following blood donation. These results have implications for improving functional capacity following blood loss.We thank James White Drinks (Ipswich, UK) for donating the juices used in the study. We also thank Matthew Black, James Kelly, and Daryl Wilkerson for assistance with data processing

Time-trial performance is not impaired in either competitive athletes or untrained individuals following a prolonged cognitive task

This is the final version. Available from Springer via the DOI in this record.It has been reported that mental fatigue decreases exercise performance during high-intensity constant-work-rate exercise (CWR) and self-paced time trials (TT) in recreationally-trained individuals. The purpose of this study was to determine whether performance is impaired following a prolonged cognitive task in individuals trained for competitive sport. Ten trained competitive athletes (ATH) and ten untrained healthy men (UNT) completed a 6-min severe-intensity CWR followed by a 6-min cycling TT immediately following cognitive tasks designed to either perturb (Stroop colour-word task and N-back task; PCT) or maintain a neutral (documentary watching; CON) mental state. UNT had a higher heart rate (75 ± 9 v. 69 ± 7 bpm; P = 0.002) and a lower positive affect PANAS score (19.9 ± 7.5 v. 24.3 ± 4.6; P = 0.036) for PCT compared to CON. ATH showed no difference in heart rate, but had a higher negative affect score for PCT compared to CON (15.1 ± 3.7 v. 12.2 ± 2.7; P = 0.029). Pulmonary O 2 uptake during CWR was not different between PCT and CON for ATH or UNT. Work completed during TT was not different between PCT and CON for ATH (PCT 103 ± 12 kJ; CON 102 ± 12 kJ; P > 0.05) or UNT (PCT 75 ± 11 kJ; CON 74 ± 12 kJ; P > 0.05). Compared to CON, during PCT, UNT showed unchanged psychological stress responses, whereas ATH demonstrated increased psychological stress responses. However, regardless of this distinction, exercise performance was not affected by PCT in either competitive athletes or untrained individuals

Interventions for involving older patients with multimorbidity in decision‐making during primary care consultations

This is the final version. Available from Wiley via the DOI in this record. Background The number of older people with more than one long-term health problem is steadily increasing worldwide. Such individuals can have complicated healthcare needs. Although they frequently want to be involved in making decisions about their health care, they are less often involved than younger, healthier people. As a result, they may not be offered the same treatment options. Review question We reviewed available evidence about the effects of interventions intended to involve older people with more than one long-term health problem in decision-making about their health care during primary care consultations. Study characteristics We included research published up until August 2018. We found three relevant studies involving 1879 participants. These studies were reported from three countries. Participants were over 65 years of age with three or more long-term health problems on average. Interventions investigated included: · patient workshops and individual patient coaching; · patient coaching including cognitive-behavioural therapy; and Selection criteria We sought randomised controlled trials (RCTs), cluster-RCTs, and quasi-RCTs of interventions to involve patients in decision-making about their health care versus usual care/control/another intervention, for patients aged 65 years and older with multi-morbidity in primary care. Data collection and analysis We used standard Cochrane methodological procedures. Meta-analysis was not possible; therefore we prepared a narrative synthesis. Main results We included three studies involving 1879 participants: two RCTs and one cluster-RCT. Interventions consisted of: · patient workshop and individual coaching using behaviour change techniques; · whole-person patient review, practitioner training, and organisational changes. All studies were funded by national research bodies. Key results None of the studies reported the main outcome ‘patient involvement in decision-making about their health care’ nor whether there was less patientinvolvement as a result ofthe intervention. Interventions were notfound to increase adverse outcomes such as death, anxiety, emergency department attendance, or hospital admissions.. We are uncertain whetherinterventions forinvolving older people with more than one long-term health problem in decision-making about their health care can improve their self-rated health or healthcare engagement, or make any difference in self-efficacy (one's belief in one's ability to succeed in specific situations) or in the overall number of general practice visits. We can report that these interventions probably make little or no difference in patients' quality of life but probably increase the number of patients discussing their priorities, and are associated with more patient consultations with nurses, when compared to usual care. Interventions may be associated with more changes in the management of health conditions when considered from the patient’s perspective when compared with a control group. The quality of the evidence was limited by small studies, and by studies choosing to measure different outcomes, resulting in lack of data that could be combined in analyses. Conclusions Further research in this developing area is required before firm conclusions can be drawnNational Institute for Health Research (NIHR

Influence of dietary nitrate supplementation on physiological and muscle metabolic adaptations to sprint interval training

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this record.We hypothesized that 4 wk of dietary nitrate supplementation would enhance exercise performance and muscle metabolic adaptations to sprint interval training (SIT). Thirty-six recreationally active subjects, matched on key variables at baseline, completed a series of exercise tests before and following a 4-wk period in which they were allocated to one of the following groups: 1) SIT and NO3--depleted beetroot juice as a placebo (SIT+PL); 2) SIT and NO3--rich beetroot juice (∼13 mmol NO3-/day; SIT+BR); or 3) no training and NO3--rich beetroot juice (NT+BR). During moderate-intensity exercise, pulmonary oxygen uptake was reduced by 4% following 4 wk of SIT+BR and NT+BR (P 0.05). The relative proportion of type IIx muscle fibers in the vastus lateralis muscle was reduced in SIT+BR only (P < 0.05). These findings suggest that BR supplementation may enhance some aspects of the physiological adaptations to SIT. NEW & NOTEWORTHY We investigated the influence of nitraterich and nitrate-depleted beetroot juice on the muscle metabolic and physiological adaptations to 4 wk of sprint interval training. Compared with placebo, dietary nitrate supplementation reduced the O2 cost of submaximal exercise, resulted in greater improvement in incremental (but not severe-intensity) exercise performance, and augmented some muscle metabolic adaptations to training. Nitrate supplementation may facilitate some of the physiological responses to sprint interval training.PepsiC

Muscle metabolic and neuromuscular determinants of fatigue during cycling in different exercise intensity domains.

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.The lactate or gas exchange threshold (GET) and the critical power (CP) are closely associated with human exercise performance. We tested the hypothesis that the limit of tolerance (Tlim) during cycle exercise performed within the exercise intensity domains demarcated by GET and CP is linked to discrete muscle metabolic and neuromuscular responses. Eleven males performed a ramp incremental exercise test, 4-5 severe-intensity (SEV; >CP) constant-work-rate (CWR) tests until Tlim, a heavy-intensity (HVY; GET) CWR test until Tlim, and a moderate-intensity (MOD; 0.05) muscle metabolic milieu (i.e., low pH and [PCr] and high [lactate]) was attained at Tlim (~2-14 min) for all SEV exercise bouts. The muscle metabolic perturbation was greater at Tlim following SEV compared to HVY, and also following SEV and HVY compared to MOD (all P0.05). Neural drive to the VL increased during SEV (4±4%; P0.05). During SEV and HVY, but not MOD, the rates of change in M-wave amplitude and neural drive were correlated with changes in muscle metabolic ([PCr], [lactate]) and blood ionic/acid-base status ([lactate], [K(+)]) (P<0.05). The results of this study indicate that the metabolic and neuromuscular determinants of fatigue development differ according to the intensity domain in which the exercise is performed

Validation of the Kinetik Blood Pressure Monitor-Series 1 for use in adults at home and in clinical settings, according to the 2002 European Society of Hypertension International Protocol on the validation of blood pressure devices

The aim of this study was to assess the blood pressure (BP) measurement accuracy of the Kinetik Blood Pressure Monitor—Series 1 (BPM-1) for use in home or clinical settings according to the 2002 European Society of Hypertension International Protocol (ESH-IP). Forty-two participants were recruited to fulfil the required number of systolic and diastolic BP measurements according to the ESH-IP. Nine sequential same-arm BP readings were measured and analysed for each participant using the test device and observer mercury standard readings according to the 2002 ESH-IP. Forty one participants were used to obtain 33 sets of systolic and diastolic BP readings and were included in the analysis. Mean difference between the device measurements and the observer (mercury standard) measurements was 1.1 ± 7.2/1.1 ± 6.8 mmHg (mean ± standard deviation; systolic/diastolic). The number of systolic BP differences between the test and observer measurements that fell within 5, 10 and 15 mmHg was 65, 86 and 92. For diastolic readings, the number of test—observer measurement differences within 5, 10 and 15 mmHg was 77, 91 and 94. The number of participants with at least two out of three differences within 5 mmHg was 28 for systolic and 40 for diastolic BP readings. Three participants had no differences between the test and observer measurements within 5 mmHg in both the systolic and diastolic measurement categories. The Kinetik BPM-1 device fulfilled the requirements of the ESH-IP validation procedure and can be recommended for clinical use and self-measurement within the home

Muscle metabolic and neuromuscular determinants of fatigue during cycling in different exercise intensity domains.

Lactate or gas exchange threshold (GET) and critical power (CP) are closely associated with human exercise performance. We tested the hypothesis that the limit of tolerance (Tlim) during cycle exercise performed within the exercise intensity domains demarcated by GET and CP is linked to discrete muscle metabolic and neuromuscular responses. Eleven men performed a ramp incremental exercise test, 4-5 severe-intensity (SEV; >CP) constant-work-rate (CWR) tests until Tlim, a heavy-intensity (HVY; GET) CWR test until Tlim, and a moderate-intensity (MOD; 0.05) muscle metabolic milieu (i.e., low pH and [PCr] and high [lactate]) was attained at Tlim (approximately 2-14 min) for all SEV exercise bouts. The muscle metabolic perturbation was greater at Tlim following SEV compared with HVY, and also following SEV and HVY compared with MOD (all P 0.05). Neural drive to the VL increased during SEV (4 ± 4%; P 0.05). During SEV and HVY, but not MOD, the rates of change in M-wave amplitude and neural drive were correlated with changes in muscle metabolic ([PCr], [lactate]) and blood ionic/acid-base status ([lactate], [K(+)]) (P < 0.05). The results of this study indicate that the metabolic and neuromuscular determinants of fatigue development differ according to the intensity domain in which the exercise is performed.NEW & NOTEWORTHY The gas exchange threshold and the critical power demarcate discrete exercise intensity domains. For the first time, we show that the limit of tolerance during whole-body exercise within these domains is characterized by distinct metabolic and neuromuscular responses. Fatigue development during exercise greater than critical power is associated with the attainment of consistent "limiting" values of muscle metabolites, whereas substrate availability and limitations to muscle activation may constrain performance at lower intensities