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Hypertension is recognised as a leading attributable risk factor for cardiovascular disease and premature mortality. Global initiatives towards the prevention and treatment of arterial hypertension are centred around non-pharmacological lifestyle modification. Exercise recommendations differ between professional and scientific organisations, but are generally unanimous on the primary role of traditional aerobic and dynamic resistance exercise. In recent years, isometric exercise training (IET) has emerged as an effective novel exercise intervention with consistent evidence of reductions in blood pressure (BP) superior to that reported from traditional guideline-recommended exercise modes. Despite a wealth of emerging new data and endorsement by select governing bodies, IET remains underutilised and is not widely prescribed in clinical practice. This expert-informed review critically examines the role of IET as a potential adjuvant tool in the future clinical management of BP. We explore the efficacy, prescription protocols, evidence quality and certainty, acute cardiovascular stimulus, and physiological mechanisms underpinning its anti-hypertensive effects. We end the review with take-home suggestions regarding the direction of future IET research.

Isometric exercise (IE) interventions are an effective non-medical method of reducing arterial blood pressure (BP). Current methods of prescribing and controlling isometric exercise intensity often require the use of expensive equipment and specialist knowledge. However, ratings of perceived exertion (RPE) may provide a more accessible means of monitoring exercise intensity. Therefore, the aim of this study was to assess the validity of a specific Isometric Exercise Scale (IES) during a continuous incremental IE test. Twenty-nine male participants completed four incremental isometric wall squat tests. Each test consisted of five 2-min stages of progressively increasing workload. Workload was determined by knee joint angle from 135° to 95°. The tests were continuous with no rest periods between the stages. Throughout the exercise protocol, RPE (IES and Borg’s CR-10), heart rate and blood pressure were recorded. A strong positive linear relationship was found between the IES and the CR-10 (r = 0.967). Likewise, strong positive relationships between the IES and wall squat duration (r = 0.849), HR (r = 0.819) and BP (r = 0.841) were seen. Intra-class correlation coefficients and coefficients of variations for the IES ranged from r = 0.81 to 0.91 and 4.5–54%, respectively, with greater reliability seen at the higher workloads. The IES provides valid and reliable measurements of RPE, exercise intensity, and the changes in physiological measures of exertion during continuous incremental IE; as such, the IES can be used as an accessible measure of exercise intensity during IE interventions.

No previous studies have examined the effects of isometric training intensity upon resting blood pressure (BP). The aims of this study were (a) to compare the effects of leg isometric training, performed at two intensities, upon resting systolic-SBP, diastolic-DBP and mean arterial-MAP BP; and (b) to examine selected cardiovascular variables, in an attempt to explain any changes in resting BP following training. Thirty-three participants were randomly allocated to either control, high- (HI) or low-intensity (LI) training for 8 weeks. Participants performed 4 × 2 min exercise bouts 3× weekly. Resting BP was measured at baseline, 4-weeks and post-training. SBP, DBP and MAP fell significantly in both groups after training. Changes were –5.2 ± 4.0, –2.6 ± 2.9 and –2.5 ± 2.2 mmHg [HI]; –3.7 ± 3.7, –2.5 ± 4.8 and –2.6 ± 2.5 mmHg [LI] for SBP, DBP and MAP, respectively. There were no significant changes in BP at 4 weeks. No significant changes were observed in any of the other cardiovascular variables examined. These findings suggest that isometric training causes reductions in SBP, DBP and MAP at a range of exercise intensities, when it is performed over 8 weeks. Furthermore, it is possible to reduce resting BP using a much lower isometric exercise intensity than has previously been shown.

Purpose High intensity interval training (HIIT) has been shown to improve important health parameters, including aerobic capacity, blood pressure, cardiac autonomic modulation and left ventricular (LV) mechanics. However, adaptations in left atrial (LA) mechanics and aortic stiffness remain unclear. Methods Forty-one physically inactive males and females were recruited. Participants were randomised to either a 4-week HIIT intervention ( n  = 21) or 4-week control period ( n  = 20). The HIIT protocol consisted of 3 × 30-s maximal cycle ergometer sprints with a resistance of 7.5% body weight, interspersed with 2-min of active unloaded recovery, three times per week. Speckle tracking imaging of the LA and M-Mode tracing of the aorta was performed pre and post HIIT and control period. Results Following HIIT, there was significant improvement in LA mechanics, including LA reservoir (13.9 ± 13.4%, p  = 0.033), LA conduit (8.9 ± 11.2%, p  = 0.023) and LA contractile (5 ± 4.5%, p  = 0.044) mechanics compared to the control condition. In addition, aortic distensibility (2.1 ± 2.7 cm 2  dyn −1  10 3 , p  = 0.031) and aortic stiffness index (− 2.6 ± 4.6, p  = 0.041) were improved compared to the control condition. In stepwise linear regression analysis, aortic distensibility change was significantly associated with LA stiffness change R 2 of 0.613 ( p  = 0.002). Conclusion A short-term programme of HIIT was associated with a significant improvement in LA mechanics and aortic stiffness. These adaptations may have important health implications and contribute to the improved LV diastolic and systolic mechanics, aerobic capacity and blood pressure previously documented following HIIT.

Isometric exercise (IE) training has been shown to reduce resting arterial blood pressure (ABP) in hypertensive, prehypertensive, and normotensive populations. However, the acute hemodynamic response of the heart to such exercise remains unclear. We therefore performed a comprehensive assessment of cardiac structure, function, and mechanics at rest and immediately post a single IE session in 26 male (age 44.8 ± 8.4 years) prehypertensive participants. Conventional echocardiography recorded standard and tissue Doppler measures of left ventricular (LV) structure and function. Speckle tracking echocardiography was used to measure LV global longitudinal, circumferential, and radial strain and strain rate. From this data, apical and basal rotation and rotational velocities, LV twist, systolic twist velocity, untwist velocity, and torsion were determined. IE led to a significant post exercise reduction in systolic (132.6 ± 5.6 vs. 109.4 ± 19.6 mmHg, P < 0.001) and diastolic (77.6 ± 9.4 vs. 58.8 ± 17.2 mmHg, P < 0.001) blood pressure, with no significant change in heart rate (62 ± 9.4 vs. 63 ± 7.5b·min−1, P = 0.63). There were significant reductions in LV end systolic diameter (3.4 ± 0.2 vs. 3.09 ± 0.3 cm, P = 0.002), LV posterior wall thickness (0.99 ± 0.1 vs. 0.9 ± 0.1 cm, P = 0.013), relative wall thickness (0.4 ± 0.06 vs. 0.36 ± 0.05, P = 0.027) estimated filling pressure (E/E' ratio 6.08 ± 1.87 vs. 5.01 ± 0.82, P = 0.006) and proportion of participants with LV concentric remodeling (30.8% vs. 7.8%, P = 0.035), and significant increases in LV ejection fraction (60.8 ± 3 vs. 68.3 ± 4%, P < 0.001), fractional shortening (31.6 ± 4.5 vs. 39.9 ± 5%, P < 0.001), cardiac output (4.3 ± 0.7 vs. 6.1 ± 1L·min−1, P < 0.001), and stroke volume (74.6 ± 11 vs. 96.3 ± 13.5 ml, P < 0.001). In this setting, there were significant increases in global longitudinal strain (−17.8 ± 2.4 vs. −20 ± 1.8%, P = 0.002) and strain rate (−0.88 ± 0.1 vs. −1.03 ± 0.1%, P < 0.001), basal rotation (−5 ± 3.5 vs. −7.22 ± 3.3°, P = 0.047), basal systolic rotational velocity (−51 ± 21.9 vs. −79.3 ± 41.3°·s−1, P = 0.01), basal diastolic rotational velocity (48.7 ± 18.9 vs. 62.3 ± 21.4°·s−1, P = 0.042), LV twist (10.4 ± 5.8 vs. 13.8 ± 5°, P = 0.049), systolic twist velocity (69.6 ± 27.5 vs. 98.8 ± 35.8°·s−1, P = 0.006), and untwist velocity (−64.2 ± 23 vs. −92.8 ± 38°·s−1, P = 0.007). These results suggest that IE improves LV function and mechanics acutely. This may in turn be partly responsible for the observed reductions in ABP following IE training programs and may have important implications for clinical populations. Arterial hypertension is a significant global public health problem and is associated with considerable morbidity and mortality. Isometric exercise training interventions have produced greater reductions in arterial blood pressure compared to alternative exercise training modalities; however, the hemodynamic response of the heart to such exercise remains unknown. This study demonstrated that isometric exercise produces acute favorable alterations in cardiac function and mechanics, which may be mechanistically linked to the observed reductions in arterial blood pressure following isometric exercise training programs. The improved cardiac responses may have important implications for clinical populations.

The aim of the study was to assess the reliability of sprint performance in both field and laboratory conditions. Twenty-one male (mean ± s: 19 ± 1 years, 1.79 ± 0.07 m, 77.6 ± 7.1 kg) and seventeen female team sport players (mean ± s: 21 ± 4 years, 1.68 ± 0. 07 m, 62.7 ± 4.7 kg) performed a maximal 20-metre sprint running test on eight separate occasions. Four trials were conducted on a non-motorised treadmill in the laboratory; the other four were conducted outdoors on a hard-court training surface with time recorded by single-beam photocells. Trials were conducted in random order with no familiarisation prior to testing. There was a significant difference between times recorded during outdoor field trials (OFT) and indoor laboratory trials (ILT) using a non-motorised treadmill (3.47 ± 0.53 vs. 6.06 ±1.17s; p < 0.001). The coefficient of variation (CV) for time was 2.55-4.22% for OFT and 5.1-7.2% for ILT. During ILT peak force (420.9 ± 87.7N), mean force (147.2 ± 24.7N), peak power (1376.8 ± 451.9W) and mean power (514.8 ± 164.4W), and were measured. The CV for all ILT variables was highest during trial 1-2 comparison. The CV (95% confidence interval) for the trial 3-4 comparison yielded: 9.4% (7.7-12. 1%), 7.9% (6.4-10.2%), 10.1% (8.2-13.1%) and 6.2% (5.1-8.0%) for PF, MF, PP and MP and respectively. The results indicate that reliable data can be derived for single maximal sprint measures, using fixed distance protocols. However, significant differences in time/speed over 20-m exist between field and laboratory conditions. This is primarily due to the frictional resistance in the non- motorised treadmill. Measures of force and power during ILT require at least 3 familiarisations to reduce variability in test scores. Key pointsReliable data can be derived from single maximal sprint measures in both indoor and outdoor environments using fixed distance protocols.There may be significant time differences to complete fixed distance trials between the two environments.Measures of mean force, peak force and peak power during indoor trials may require multiple trials to reduce variability in test scores.

The placebo effect, a positive outcome resulting from the belief that a beneficial treatment has been received, is widely acknowledged but little understood. It has been suggested that placebo responsiveness, the degree to which an individual will respond to a placebo, might vary in the population. The study aimed to identify placebo-responsive participants from a previously published paper that examined the effects of caffeine and placebos on cycling performance. A quantitative model of placebo responsiveness was defined. 14 male participants were subsequently classified as either placebo responsive or non-responsive. Interviews were conducted to corroborate these classifications. Secondary quantitative analyses of performance data were conducted to identify further placebo responses. Finally, the five factor model of personality was used to explore relationships between personality and placebo responsiveness. Overall, 5 of 14 participants were classified as placebo responsive. Performance data suggested that 2 participants were placebo responsive whilst 12 were not. Interview data corroborated experimental data for these participants and for 9 of the remainder, however it suggested that the remaining 3 had experienced placebo effects. Secondary quantitative analysis revealed that performance for these 3 participants, whilst no better than for non-responsive participants, was associated with substantially increased oxygen uptake in the 2 conditions in which participants believed caffeine had been administered (7.0% ± 15.1; 95% confidence intervals -2.6 to 16.7, and 6.0% ± 15.4; -3.9 to 15.9 respectively). Finally, data suggested that the personality factors of extroversion, agreeableness, openness and neuroticism may relate to placebo responding. Placebo effects such as pain tolerance and fatigue resistance might be experienced by a percentage of participants but might not always be manifest in objective measures of performance. Key pointsBeliefs can have both positive (placebo) and negative (nocebo) effectsPlacebo effects may be experienced both objectively and subjectivelyCertain personality traits may be related to placebo respondingA multi-method approach may best elucidate placebo effects in sport.

The aim of this study was to evaluate the impact of a novel crank system on laboratory time-trial cycling performance. The Rotor system makes each pedal independent from the other so that the cranks are no longer fixed at 180°. Twelve male competitive but non-elite cyclists (mean ± s: 35 ± 7 yr, Wmax = 363 ± 38 W, VO2peak = 4.5 ± 0.3 L·min(-1)) completed 6-weeks of their normal training using either a conventional (CON) or the novel Rotor (ROT) pedal system. All participants then completed two 40.23-km time-trials on an air-braked ergometer, one using CON and one using ROT. Mean performance speeds were not different between trials (CON = 41.7 km·h(-1) vs. ROT = 41.6 km·h(-1), P > 0.05). Indeed, the pedal system used during the time-trials had no impact on any of the measured variables (power output, cadence, heart rate, VO2, RER, gross efficiency). Furthermore, the ANOVA identified no significant interaction effect between main effects (Time-trial crank system*Training crank system, P > 0.05). To the authors' knowledge, this is the first study to examine the effects of the Rotor system on endurance performance rather than endurance capacity. These results suggest that the Rotor system has no measurable impact on time-trial performance. However, further studies should examine the importance of the Rotor 'regulation point' and the suggestion that the Rotor system has acute ergogenic effects if used infrequently. Key pointsThe Rotor crank system does not improve gross efficiency in well-trained cyclists.The Rotor crank system has no measurable impact on laboratory 40.23-km time-trial performance.A 6-week period of familiarisation does not increase the effectiveness of the Rotor crank system.

This study examined the therapeutic effects of an inert placebo gel on experimentally induced muscle pain in a sports therapy setting. It aimed to investigate the degree to which conditioned analgesia, coupled with an expectation of intervention, was a factor in subsequent analgesia. Participants were sixteen male and eight female sports therapy students at a UK University. With institutional ethics board approval and following informed consent procedures, each was exposed to pain stimulus in the lower leg in five conditions, ie, conditioning, prebaseline, experimental (two placebo gel applications), and postbaseline. In conditioning trials, participants identified a level of pain stimulus equivalent to a perceived pain rating of 6/10. An inert placebo gel was then applied to the site with the explicit instruction that it was an analgesic. Participants were re-exposed to the pain stimulus, the level of which, without their knowledge, had been decreased, creating the impression of an analgesic effect resulting from the gel. In experimental conditions, the placebo gel was applied and the level of pain stimulus required to elicit a pain rating of 6/10 recorded. Following application of the placebo gel, the level of pain stimulus required to elicit a pain rating of 6/10 increased by 8.2%. Application of the placebo gel significantly decreased participant's perceptions of muscle pain (P = 0.001). Subjects' experience and expectation of pain reduction may be major factors in the therapeutic process. These factors should be considered in the sports therapeutic environment.

Current Aβ-targeting therapeutics for Alzheimer’s disease (AD) only slow cognitive decline due to poor understanding of AD pathogenesis. Here we describe a mechanism of AD pathogenesis in which the histone methyltransferase G9a noncanonically regulates translation of hippocampal proteins associated with AD pathology. Correspondingly, we developed a brain-penetrant inhibitor of G9a, MS1262, which restored both age-related learning & memory and noncognitive functions in multiple AD mouse models. Further, comparison of AD pathology-correlated mouse proteomes with those of AD patients found G9a regulates pathological pathways that promote Aβ and neurofibrillary tangles. This mouse-to-human overlap of G9a regulated AD-associated pathologic proteins supports at the molecular level the efficacy of targeting G9a translational mechanism for treating AD patients. Additionally, MS1262 treatment reversed the AD-characteristic expression or phosphorylation of multiple clinically validated biomarkers of AD that have the potential to be used for early-stage AD diagnosis and companion diagnosis of individualized drug effects. The authors describe a new mechanism of AD pathogenesis in which the histone methylase G9a regulates translation of hippocampal proteins associated with AD pathology. Targeting this mechanism with a brain-penetrant inhibitor of G9a helped rescue brain pathology in AD mouse models.