Left ventricular mechanical, cardiac autonomic and metabolic responses to a single session of high intensity interval training.

High-intensity interval training (HIIT) produces significant health benefits. However, the acute physiological responses to HIIT are poorly understood. Therefore, we aimed to measure the acute cardiac autonomic, haemodynamic, metabolic and left ventricular mechanical responses to a single HIIT session. Fifty young, healthy participants completed a single HIIT session, comprising of three 30-s maximal exercise intervals on a cycle ergometer, interspersed with 2-min active recovery. Cardiac autonomics, haemodynamics and metabolic variables were measured pre-, during and post-HIIT. Conventional and speckle tracking echocardiography was used to record standard and tissue Doppler measures of left ventricular (LV) structure, function and mechanics pre- and post-HIIT. Following a single HIIT session, there was significant post-exercise systolic hypotension (126 ± 13 to 111 ± 10 mmHg, p < 0.05), parallel to a significant reduction in total peripheral resistance (1640 ± 365 to 639 ± 177 dyne⋅s⋅cm , p < 0.001) and significant increases in baroreceptor reflex sensitivity and baroreceptor effectiveness index (9.2 ± 11 to 24.8 ± 16.7 ms⋅mmHg and 41.8 ± 28 to 68.8 ± 16.2, respectively) during recovery compared to baseline. There was also a significant increase in the low- to high-frequency heart rate variability ratio in recovery (0.7 ± 0.48 to 1.7 ± 1, p < 0.001) and significant improvements in left ventricular global longitudinal strain (- 18.3 ± 1.2% to - 29.2 ± 2.3%, p < 0.001), and myocardial twist mechanics (1.27 ± 0.72 to 1.98 ± 0.72°·cm , p = 0.028) post-HIIT compared to baseline. A single HIIT session is associated with acute improvements in autonomic modulation, haemodynamic cardiovascular control and left ventricular function, structure and mechanics. The acute responses to HIIT provide crucial mechanistic information, which may have significant acute and chronic clinical implications. [Abstract copyright: © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

An evidence-based guide to the efficacy and safety of isometric resistance training in hypertension and clinical implications.

More than 30 randomized controlled trials, supported by individual patient-level and group-level meta-analyses and a Delphi analysis of expert opinion, unequivocally show isometric resistance training (IRT) elicits antihypertensive benefits in healthy people and those with chronic illness. We aim to provide efficacy and safety evidence, and a guide for IRT prescription and delivery. Recommendations are made for the use of IRT in specific patient populations and appropriate methods for IRT delivery. Published data suggest IRT consistently elicits mean blood pressure reductions of 7.4/3.3 mmHg systolic blood pressure/diastolic blood pressure, equivalent to antihypertensive medication monotherapy. Blood pressure reductions of this size are associated with an approximate 13% to 22% reduction in major cardiovascular events. Moreover, IRT is safe in a range of patient populations. We suggest that IRT has the greatest potential benefit when used as an antihypertensive therapy in individuals unwilling and/or unable to complete aerobic exercise, or who have had limited adherence or success with it; individuals with resistant or uncontrolled hypertension, already taking at least two pharmacological antihypertensive agents; and healthy or clinical populations, as an adjunct to aerobic exercise and dietary intervention in those who have not yet attained control of their hypertension. IRT is efficacious and produces clinically meaningful blood pressure reductions (systolic blood pressure, 7 mmHg; diastolic blood pressure, 3 mmHg). IRT is safe and typical program delivery requires only about 17 min weekly. IRT should be used as an adjunct to other exercise modalities, in people unable to complete other types of exercise, or in resistant hypertension. [Abstract copyright: © 2023. The Author(s).

Blood pressure and cardiac autonomic adaptations to isometric exercise training: A randomized sham‐controlled study

Isometric exercise training (IET) is increasingly cited for its role in reducing resting blood pressure (BP). Despite this, few studies have investigated a potential sham effect attributing to the success of IET, thus dictating the aim of the present study. Thirty physically inactive males (n = 15) and females (n = 15) were randomly assigned into three groups. The IET group completed a wall squat intervention at 95% peak heart rate (HR) using a prescribed knee joint angle. The sham group performed a parallel intervention, but at an intensity (<75% peak HR) previously identified to be inefficacious over a 4-week training period. No-intervention controls maintained their normal daily activities. Pre- and post-measures were taken for resting and continuous blood pressure and cardiac autonomic modulation. Resting clinic and continuous beat-to-beat systolic (−15.2 ± 9.2 and −7.3 ± 5.6 mmHg), diastolic (−4.6 ± 5 and −4.5 ± 5.1), and mean (−7 ± 4.2 and −7.5 ± 5.3) BP, respectively, all significantly decreased in the IET group compared to sham and no-intervention control. The IET group observed a significant decrease in low-frequency normalized units of heart rate variability concurrent with a significant increase in high-frequency normalized units of heart rate variability compared to both the sham and no-intervention control groups. The findings of the present study reject a nonspecific effect and further support the role of IET as an effective antihypertensive intervention. Clinical Trials ID: NCT05025202

Blood pressure and cardiac autonomic adaptations to isometric exercise training: A randomized sham-controlled study

Isometric exercise training (IET) is increasingly cited for its role in reducing resting blood pressure (BP). Despite this, few studies have investigated a potential sham effect attributing to the success of IET, thus dictating the aim of the present study. Thirty physically inactive males (n=15) and females (n=15) were randomly assigned into 3 groups. The IET group completed a wall-squat intervention at 95% peak heart rate (HR) using a prescribed knee joint angle. The sham group performed a parallel intervention, but at an intensity (<75% peak HR) previously identified to be inefficacious over a 4-week training period. No-intervention controls maintained their normal daily activities. Pre- and post-measures were taken for resting and continuous blood pressure and cardiac autonomic modulation. Resting clinic and continuous beat to beat systolic (-15.2±9.2 and -7.3±5.6 mmHg), diastolic (-4.6±5 and -4.5±5.1) and mean (-7±4.2 and -7.5±5.3) BP, respectively, all significantly decreased in the IET group compared to sham and no-intervention control. The IET group observed a significant decrease in low frequency normalised units of heart rate variability concurrent with a significant increase in high frequency normalised units of heart rate variability compared to both the sham and no-intervention control groups. The findings of the present study reject a non-specific effect and further support the role of IET as an effective anti-hypertensive intervention

An evidence-based guide to the efficacy and safety of isometric resistance training in hypertension and clinical implications

More than 30 randomized controlled trials, supported by individual patient-level and group-level meta-analyses and a Delphi analysis of expert opinion, unequivocally show isometric resistance training (IRT) elicits antihypertensive benefits in healthy people and those with chronic illness. We aim to provide efficacy and safety evidence, and a guide for IRT prescription and delivery. Recommendations are made for the use of IRT in specific patient populations and appropriate methods for IRT delivery. Published data suggest IRT consistently elicits mean blood pressure reductions of 7.4/3.3 mmHg systolic blood pressure/diastolic blood pressure, equivalent to antihypertensive medication monotherapy. Blood pressure reductions of this size are associated with an approximate 13% to 22% reduction in major cardiovascular events. Moreover, IRT is safe in a range of patient populations. We suggest that IRT has the greatest potential benefit when used as an antihypertensive therapy in individuals unwilling and/or unable to complete aerobic exercise, or who have had limited adherence or success with it; individuals with resistant or uncontrolled hypertension, already taking at least two pharmacological antihypertensive agents; and healthy or clinical populations, as an adjunct to aerobic exercise and dietary intervention in those who have not yet attained control of their hypertension. IRT is efficacious and produces clinically meaningful blood pressure reductions (systolic blood pressure, 7 mmHg; diastolic blood pressure, 3 mmHg). IRT is safe and typical program delivery requires only about 17 min weekly. IRT should be used as an adjunct to other exercise modalities, in people unable to complete other types of exercise, or in resistant hypertension

Home-based isometric exercise training induced reductions resting blood pressure

Purpose: Isometric exercise training (IET) reduces resting blood pressure (BP). Most previous protocols impose exercise barriers which undermine its effectiveness as a potential physical therapy for altering BP. An inexpensive, home-based programme would promote IET as a valuable tool in the fight against hypertension. The aims of this study were: (a) to investigate whether home-based wall squat training could successfully reduce resting BP, and (b) to explore the physiological variables that might mediate a change in resting BP. Methods: Twenty-eight healthy normotensive males were randomly assigned to a control and a 4 week home-based IET intervention using a crossover design with a 4 week ‘washout’ period in-between. Wall squat training was completed 3x weekly over 4 weeks with 48 hours between sessions. Each session comprised 4x 2 minute bouts of wall squat exercise performed at a participant-specific knee joint angle relative to a target HR of 95% HRpeak, with 2 minutes rest between bouts. Resting heart rate, BP, cardiac output, total peripheral resistance and stroke volume were taken at baseline and post each condition. Results: Resting BP (systolic = -4 ± 5, diastolic = -3 ± 3 and mean arterial = -3 ± 3 mmHg), cardiac output (-0.54 ± 0.66 L∙min-1) and heart rate (-5 ± 7 beats∙min-1) were all reduced following IET, with no change in total peripheral resistance or stroke volume compared to the control. Conclusion: These findings suggest the wall squat provides an effective method for reducing resting BP in the home resulting primarily from a reduction in resting heart rate

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale