scholarly journals Directions for Exercise Treatment Response Heterogeneity and Individual Response Research

2021 ◽  
Author(s):  
Travis J. Hrubeniuk ◽  
Jacob T. Bonafiglia ◽  
Danielle R. Bouchard ◽  
Brendon J. Gurd ◽  
Martin Sénéchal
Keyword(s):  
Personalized Medicine ◽  
Exercise Training ◽  
Treatment Response ◽  
Study Design ◽  
Analytical Approach ◽  
Individual Response ◽  
Comprehensive Understanding ◽  
Response Variation ◽  
Response To Exercise ◽  
The Impact

AbstractTreatment response heterogeneity and individual responses following exercise training are topics of interest for personalized medicine. Proposed methods to determine the contribution of exercise to the magnitude of treatment response heterogeneity and categorizing participants have expanded and evolved. Setting clear research objectives and having a comprehensive understanding of the strengths and weaknesses of the available methods are vital to ensure the correct study design and analytical approach are used. Doing so will ensure contributions to the field are conducted as rigorously as possible. Nonetheless, concerns have emerged regarding the ability to truly isolate the impact of exercise training, and the nature of individual responses in relation to mean group changes. The purpose of this review is threefold. First, the strengths and limitations associated with current methods for quantifying the contribution of exercise to observed treatment response heterogeneity will be discussed. Second, current methods used to categorize participants based on their response to exercise will be outlined, as well as proposed mechanisms for factors that contribute to response variation. Finally, this review will provide an overview of some current issues at the forefront of individual response research.

Sympathetic neural responses in heart failure during exercise and after exercise training

2021 ◽  
Vol 135 (4) ◽  
pp. 651-669
Author(s):  
Catherine F. Notarius ◽  
John S. Floras
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Sympathetic Nerve ◽  
Cardiovascular Response ◽  
Future Research ◽  
Human Heart Failure ◽  
Reduced Ejection Fraction ◽  
Direct Measurements ◽  
Response To Exercise ◽  
The Impact

Abstract The sympathetic nervous system coordinates the cardiovascular response to exercise. This regulation is impaired in both experimental and human heart failure with reduced ejection fraction (HFrEF), resulting in a state of sympathoexcitation which limits exercise capacity and contributes to adverse outcome. Exercise training can moderate sympathetic excess at rest. Recording sympathetic nerve firing during exercise is more challenging. Hence, data acquired during exercise are scant and results vary according to exercise modality. In this review we will: (1) describe sympathetic activity during various exercise modes in both experimental and human HFrEF and consider factors which influence these responses; and (2) summarise the effect of exercise training on sympathetic outflow both at rest and during exercise in both animal models and human HFrEF. We will particularly highlight studies in humans which report direct measurements of efferent sympathetic nerve traffic using intraneural recordings. Future research is required to clarify the neural afferent mechanisms which contribute to efferent sympathetic activation during exercise in HFrEF, how this may be altered by exercise training, and the impact of such attenuation on cardiac and renal function.

scholarly journals Repeated testing for the assessment of individual response to exercise training

2018 ◽  
Vol 124 (6) ◽  
pp. 1567-1579 ◽  
Author(s):  
Anne Hecksteden ◽  
Werner Pitsch ◽  
Friederike Rosenberger ◽  
Tim Meyer
Keyword(s):  
Exercise Training ◽  
Training Trial ◽  
Training Group ◽  
Control Individual ◽  
Individual Response ◽  
Repeated Testing ◽  
Individual Level ◽  
The Individual ◽  
Response To Exercise ◽  
Analytical Approaches

Observed response to regular exercise training differs widely between individuals even in tightly controlled research settings. However, the respective contributions of random error and true interindividual differences as well as the relative frequency of nonresponders are disputed. Specific challenges of analyses on the individual level as well as a striking heterogeneity in definitions may partly explain these inconsistent results. Repeated testing during the training phase specifically addresses the requirements of analyses on the individual level. Here we report a first implementation of this innovative design amendment in a head-to-head comparison of existing analytical approaches. To allow for comparative implementation of approaches we conducted a controlled endurance training trial (1 yr walking/jogging, 3 days/wk for 45 min with 60% heart rate reserve) in healthy, untrained subjects ( n = 36, age = 46 ± 8 yr; body mass index 24.7 ± 2.7 kg/m2; V̇o2max 36.6 ± 5.4). In the training group additional V̇o2max tests were conducted after 3, 6, and 9 mo. Duration of the control condition was 6 mo due to ethical constraints. General efficacy of the training intervention could be verified by a significant increase in V̇o2max in the training group ( P < 0.001 vs. control). Individual training response of relevant magnitude (>0.2 × baseline variability in V̇o2max) could be demonstrated by several approaches. Regarding the classification of individuals, only 11 of 20 subjects were consistently classified, demonstrating remarkable disagreement between approaches. These results are in support of relevant interindividual variability in training efficacy and stress the limitations of a responder classification. Moreover, this proof-of-concept underlines the need for tailored methodological approaches for well-defined problems. NEW & NOTEWORTHY This work reports a first implementation of a repeated testing training trial for the investigation of individual response. This design amendment was recently proposed to address specifically the statistical requirements of analyses on the individual level. Moreover, a comprehensive comparison of previously published methods exemplifies the striking heterogeneity of existing approaches.

scholarly journals Individual response to exercise training - a statistical perspective

2015 ◽  
Vol 118 (12) ◽  
pp. 1450-1459 ◽  
Author(s):  
Anne Hecksteden ◽  
Jochen Kraushaar ◽  
Friederike Scharhag-Rosenberger ◽  
Daniel Theisen ◽  
Stephen Senn ◽  
...  
Keyword(s):  
Exercise Training ◽  
Predictive Accuracy ◽  
Signal To Noise Ratio ◽  
Interactive Effects ◽  
Control Group ◽  
Individual Response ◽  
Individual Level ◽  
Exercise Training Program ◽  
The Individual ◽  
Response To Exercise

In the era of personalized medicine, interindividual differences in the magnitude of response to an exercise training program (subject-by-training interaction; “individual response”) have received increasing scientific interest. However, standard approaches for quantification and prediction remain to be established, probably due to the specific considerations associated with interactive effects, in particular on the individual level, compared with the prevailing investigation of main effects. Regarding the quantification of subject-by-training interaction in terms of variance components, confounding sources of variability have to be considered. Clearly, measurement error limits the accuracy of response estimates and thereby contributes to variation. This problem is of particular importance for analyses on the individual level, because a low signal-to-noise ratio may not be compensated by increasing sample size (1 case). Moreover, within-subject variation in training efficacy may contribute to gross response variability. This largely unstudied source of variation may not be disclosed by comparison to a control group but calls for repeated interventions. A second critical point concerns the prediction of response. There is little doubt that exercise training response is influenced by a multitude of determinants. Moreover, indications of interaction between influencing factors of training efficacy lead to the hypothesis that optimal predictive accuracy may be attained using an interactive rather than additive approach. Taken together, aiming at conclusive inference and optimal predictive accuracy in the investigation of subject-by-training interaction entails specific requirements that are deducibly based on statistical principles but beset with many practical difficulties. Therefore, pragmatic alternatives are warranted.

The impact of age and socioeconomic factors on response to exercise training in patients with ischemic heart disease, heart failure and after valve replacement

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H.K Rasmusen ◽  
N Mikkelsen
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Heart Disease ◽  
Exercise Training ◽  
Oxygen Uptake ◽  
Peak Oxygen Uptake ◽  
Funding Source ◽  
Baseline Characteristics ◽  
Response To Exercise ◽  
The Impact

Abstract   The impact of baseline characteristics on response to exercise training in patients with ischemic heart disease. Background Exercise training improves peak oxygen uptake, an important predictor of mortality in patients with coronary artery disease (CAD). Unfortunately, some patients do not response with an increase in peak oxygen uptake after exercise training. If it is possible to identify these patients it would be possible to tailor their exercise training. Purpose To investigate if baseline characteristics can predict response to exercise training in patients with heart disease. Methods A retrospective analysis of 1443 CAD patients (age 64±11 y (mean (±SD)), 74% male, participated and completed an eight-week supervised outpatient exercise intervention with two weekly training sessions of 1.5 hours with high intensity interval- (&gt;80% of VO2peak) and resistance training. Patient characteristics were entered in the local database as the patients entered cardiac rehabilitation (CR). VO2peak was assessed before and after CR using a cardiopulmonary exercise test (CPET) with a maximal symptom limited bicycle ergometer test. Breathing gases were collected and analysed breath-by-breath. Each test aimed at physical exhaustion and a respiratory exchange ratio of more than 1.1 to ensure the validity of the CPET test. Patients were divided into responders defined as an improvement in aerobic capacity (change in VO2peak) after CR and non-responders if no improvement (change in VO2peak of 0.0ml/kg/min or less) post CR. We performed a multivariable logistic regression analysis using responders vs. non-responders as the endpoint. Explanatory variables were identified according to previous literature and comprised the following variables; age, sex, baseline VO2peak, tobacco use, diabetes, COPD, revascularization, working status, educational attainment, ethnicity and hypercholesteremia. Results 1097 patients were responders and 346 (24%) non-responders to the exercise training despite no difference in attendance. Logistic regression analysis of responders vs. non-responders in relation to baseline characteristics are shown in the table. Conclusion In summarize, 24% of these heart patients were exercise non-responders. High baseline VO2peak, older age, having COPD, being on disability pension, low educational attainment and non-western ethnicity were predictors of training non-response. Identification of patients with a large likelihood of non-response is a beginning towards patient tailored exercise programmes. Baseline characteristics in responders. CABG: coronary artery bypass graft; COPD: chronic obstructive pulmonary disease; PCI: percutaneous coronary intervention; SD: standard deviation; VO2peak: change in peak oxygen uptake. P-values of &lt;0.05 are considered significant and shown in bold. 95% confidence intervals are shown in last column. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Helsefonden

scholarly journals Exercise-induced expression of VEGF and salvation of myocardium in the early stage of myocardial infarction

2009 ◽  
Vol 296 (2) ◽  
pp. H389-H395 ◽  
Author(s):  
Guifu Wu ◽  
Jamal S. Rana ◽  
Joanna Wykrzykowska ◽  
Zhimin Du ◽  
Qingen Ke ◽  
...  
Keyword(s):  
Exercise Training ◽  
Exercise Group ◽  
Angiogenic Factors ◽  
Vegf Expression ◽  
Infarcted Myocardium ◽  
Sedentary Group ◽  
Exercise Preconditioning ◽  
Exercise Induced ◽  
Response To Exercise ◽  
The Impact

The mechanism of exercise-induced benefit and angiogenesis in ischemic heart disease remains poorly defined. This study was designed to investigate the effects of exercise training on the expression of angiogenic factors and angiogenesis in the infarcted myocardium [myocarial infaction (MI)]. Sixty-three male FVB mice were used for study and were divided into subgroups to test the response to exercise: the time-dependent expression of angiogenic factors to exercise training in normal ( group 1; n = 12) and infarcted myocardium ( group 2; n = 15) and the exercise-induced angiogenic response in normal and infarcted myocardium ( group 3; n = 20) as well as the impact of exercise preconditioning on infarcted myocardium ( group 4; n = 26). Exercise training consisted of daily treadmill exercise for 1 h for 3 days. Expression of VEGF and its receptors Flt-1 and Flk-1 was upregulated by exercise training in mice with MI. Exercise-induced VEGF expression in the MI group was higher than that in the sham (control) group. Cell proliferation assessment showed a significantly higher ( P < 0.05) number of bromodeoxyuridine-positive cells in post-MI mice in the exercise group as opposed to post-MI mice in the sedentary group. 2,3,5-Triphenyltetrazolium chloride staining revealed a profound difference in the size of MI (18.25 ± 2.93%) in the exercise group versus the sedentary group (29.26 ± 7.64%, P = 0.02). Moreover, exercise preconditioning before MI promoted VEGF expression at both mRNA and protein levels. In conclusion, activation of VEGF and its receptors occurs in the infarcted mice heart in response to exercise, which results in decreased infarct size and improved angiogenesis.

scholarly journals Extracellular vesicles as predictors of individual response to exercise training in youth living with obesity

2020 ◽  
Author(s):  
Taiana M. Pierdoná ◽  
Alexandria Martin ◽  
Patience O. Obi ◽  
Samira Seif ◽  
Benjamin Bydak ◽  
...  
Keyword(s):  
Resistance Training ◽  
Exercise Training ◽  
Extracellular Vesicles ◽  
Protein Yield ◽  
Outcome Variable ◽  
Individual Response ◽  
Resistance Training Program ◽  
Biophysical Profile ◽  
Matsuda Index ◽  
Response To Exercise

AbstractExercise is associated with various health benefits, including the prevention and management of obesity and cardiometabolic risk factors. However, a strong heterogeneity in the adaptive response to exercise training exists. The objective of this study was to evaluate if changes in extracellular vesicles (EVs) after acute aerobic exercise (AE) were associated with the responder phenotype following 6-weeks of resistance exercise training. This is a secondary analysis of plasma samples from the EXIT trial (clinical trial #02204670). Eleven sedentary youth with obesity (15.7±0.5 years, BMI ≥ 95th percentile) underwent an acute bout of AE (60% heart rate reserve, 45 min). Blood was collected before exercise [at time (AT) 0 min], during [AT15, 30, 45 min], and 75 min after exercise [AT120]. Afterward, youth participated in 6-week resistance training program, and were categorized into responders (RE) or non-responders (NRE) based on changes in insulin sensitivity as measured by the Matsuda Index. EVs were isolated using size exclusion chromatography (Izon®). The primary outcome variable was EV biophysical profile, which includes size, zeta potential, protein yield and expression of markers associated with EV subtypes. The variables were analyzed in a single-blind fashion. Overall, there was a general increase in EV production in both groups. Average EV size was larger in RE (~147 nm) vs. NRE (~124 nm; p<0.05). Average EV size at AT0 was associated with absolute change in Matsuda index following 6-weeks of resistance training (r=0.44, p=0.08). EV size distribution revealed RE preferentially expressed EVs between 150 – 250 nm in size, whereas NRE expressed EVs between 50 – 100 nm (p<0.05). At baseline, RE-EVs contained ~25% lower Tsg101 protein, ~85% higher MMP2 content, while CD63 levels remained unchanged between the groups. Total protein yield in RE-EVs was higher than NRE at AT15 (p<0.05). Our data suggest that youth with obesity that respond to exercise training produce larger EVs, with lower exosome- and higher microvesicle-specific protein expression. RE-EVs also had higher EV protein yield during AE. The relationship between larger EV subtypes and/or cargo, and the individual response to exercise has yet to be fully elucidated.

scholarly journals Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

2017 ◽  
Vol 97 (2) ◽  
pp. 495-528 ◽  
Author(s):  
Daniel J. Green ◽  
Maria T. E. Hopman ◽  
Jaume Padilla ◽  
M. Harold Laughlin ◽  
Dick H. J. Thijssen
Keyword(s):  
Blood Flow ◽  
Exercise Training ◽  
Vascular Function ◽  
Wall Stress ◽  
Adaptive Responses ◽  
Late 20Th Century ◽  
Hemodynamic Forces ◽  
Response To Exercise ◽  
The Impact

On the 400th anniversary of Harvey's Lumleian lectures, this review focuses on “hemodynamic” forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century discovery that endothelial cells modify arterial tone via paracrine transduction provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the interrelationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions, and the implications for human health. Exercise modifies blood flow, luminal shear stress, arterial pressure, and tangential wall stress, all of which can transduce changes in arterial function, diameter, and wall thickness. There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute to the well-established decrease in cardiovascular risk attributed to physical activity.

scholarly journals IMPACT OF INTRODUCING THE MIDDLE ALTERNATIVE: META-ANALYTIC APPROACH

2021 ◽  
Author(s):  
Radka Kubalová ◽  
Keyword(s):  
Study Design ◽  
Analytical Approach ◽  
Selection Process ◽  
Analytic Approach ◽  
Compromise Effect ◽  
Specific Product ◽  
Product Categories ◽  
The Impact ◽  
Literature Selection ◽  
Choice Set

This paper explores the impact of adding a compromise alternative into the choice set taking into account the previous findings in the literature. The paper takes a meta-analytical approach when examining the results of previously published peer-reviewed studies which included specific product categories in their study design. The literature selection process generated 69 choice set comparisons across 8 scientific studies including over 14 000 individual observations which allow examining the compromise effect in a broader view.

Exploring power in response inhibition tasks using the bootstrap: The impact of number of participants, number of trials, effect magnitude, and study design

2019 ◽  
Author(s):  
Curtis David Von Gunten ◽  
Bruce D Bartholow
Keyword(s):  
Study Design ◽  
Effect Size ◽  
Statistical Power ◽  
Bootstrap Sampling ◽  
Reliable Measure ◽  
Internal Reliability ◽  
The Impact ◽  
Power Analyses ◽  
Effect Magnitude

A primary psychometric concern with laboratory-based inhibition tasks has been their reliability. However, a reliable measure may not be necessary or sufficient for reliably detecting effects (statistical power). The current study used a bootstrap sampling approach to systematically examine how the number of participants, the number of trials, the magnitude of an effect, and study design (between- vs. within-subject) jointly contribute to power in five commonly used inhibition tasks. The results demonstrate the shortcomings of relying solely on measurement reliability when determining the number of trials to use in an inhibition task: high internal reliability can be accompanied with low power and low reliability can be accompanied with high power. For instance, adding additional trials once sufficient reliability has been reached can result in large gains in power. The dissociation between reliability and power was particularly apparent in between-subject designs where the number of participants contributed greatly to power but little to reliability, and where the number of trials contributed greatly to reliability but only modestly (depending on the task) to power. For between-subject designs, the probability of detecting small-to-medium-sized effects with 150 participants (total) was generally less than 55%. However, effect size was positively associated with number of trials. Thus, researchers have some control over effect size and this needs to be considered when conducting power analyses using analytic methods that take such effect sizes as an argument. Results are discussed in the context of recent claims regarding the role of inhibition tasks in experimental and individual difference designs.

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