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3 Effects of Interval Aerobic Training Program with Recovery bouts on cardiorespiratory
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and endurance fitness in seniors
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8 Walid Bouaziz1,2,3, Elise Schmitt1,2, Thomas Vogel1,2, François Lefebvre4, Romain
9 Remetter2,5, Evelyne Lonsdorfer2,5, Pierre-Marie Leprêtre6,7, Georges Kaltenbach1, Bernard
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11 Geny2,5, Pierre-Olivier Lang8,9
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14 1
Geriatric Department, University Hospitals of Strasbourg, Strasbourg, France.
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16 Research laboratory Mitochondria, Oxidative stress and muscle resistance (MSP, EA-3072),
17 department of Physiology, Faculty of Medicine, Strasbourg University, Strasbourg, France.
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Research Unit of the University of Rouen (CETAPS, EA-3832), Faculty of Sport Sciences, Mont
20 Saint-Aignan, France.
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Department of Medical Information, University Hospitals of Strasbourg, Strasbourg, France.
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Functional Explorations Department, University Hospitals of Strasbourg, Strasbourg, France
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Laboratory of Exercise Physiology and Rehabilitation (APERE, EA-3300), UFR-STAPS, University
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Health and Wellbeing Academy, Anglia Ruskin University, Cambridge, United Kingdom.
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Montchoisi Clinic, Lausanne, Switzerland.
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34 Corresponding author
35 Walid Bouaziz, PhD
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37 University Hospitals of Strasbourg, Geriatric Department, 83 rue Himmerich, 67091
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Strasbourg Cedex, France
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40 Phone: +33(0)3.88.11.55.24 – Fax: +33(0)3.88.11.58.21
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42 e-mail: walid.bouaziz.88@gmail.com
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47 Running head: Effects of IATP-R in sedentary seniors
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60 Scandinavian Journal of Medicine & Science in Sports - PROOF
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3 ABSTRACT
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Interval aerobic training programs (IATP) improve cardiorespiratory and endurance
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6 parameters. They are however unsuitable to seniors as frequently associated with occurrence
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8 of exhaustion and muscle pain. The purpose of this study was to measure the benefits of an
9 IATP designed with recovery bouts (IATP-R) in terms of cardiorespiratory and endurance
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11 parameters and its acceptability among seniors (≥70 years). Sedentary healthy volunteers
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were randomly assigned either to IATP-R or sedentary lifestyle. All participants performed an
14 incremental cycle exercise and 6-minute walk test (6-MWT) at baseline and 9.5 weeks later.
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16 The first ventilatory threshold (VT1); maximal tolerated power (MTP); peak of oxygen uptake
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(VO2peak); maximal heart rate (HRmax); and distance walked at 6-MWT were thus measured.
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19 IATP-R consisted of 19 sessions of 30-min (6×4-min at VT1 + 1-min at 40% of VT1) cycling
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21 exercise over 9.5 weeks. With an adherence rate of 94.7% without any significant adverse
22 events, 9.5 weeks of IATP-R, compared to controls, enhanced endurance (VT1: +18.3 vs. -
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24 4.6%; HR at baseline VT1: -5.9 vs. +0.2%) and cardiorespiratory parameters (VO2peak: +14.1
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vs. -2.7%; HRmax: +1.6 vs. -1.7%; MTP: +19.2 vs. -2.3%). The walk distance at the 6-MWT
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27 was also significantly lengthened (+11.6 vs. -3.1%). While these findings resulted from an
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interim analysis planned when 30 volunteers were enrolled in both groups, IATP-R appeared
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30 as effective, safe, and applicable among sedentary healthy seniors. These characteristics are
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32 decisive for exercise training prescription and adherence.
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3 Main text
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1. INTRODUCTION
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6 The body of evidence accumulated over the last decade report significant benefits of aerobic
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8 training (AT) on cardiorespiratory and endurance performance1,2 together with different other
9 facets of individuals’ health3. AT, commonly defined as any exercise involving movement of
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11 large muscle groups over a certain period of time (e.g., treadmill walking/running, walking,
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cycling, or dancing),4 is now part of the preventive and therapeutic approach of many chronic
14 health conditions5. Guidelines recommended maintaining active life style with a minimum of
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16 150 min moderate- or 75 min vigorous-intensity aerobic activity or an equivalent combination
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per week6.
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19 Among the different types of AT, interval AT programs (IATP) are the most efficient to
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21 improve cardiorespiratory and endurance performances, and general health7-9 including older
22 adults10,11. However, based upon our experience11, this type of program is often less well-
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24 tolerated in seniors compared to younger counterparts.12 Indeed, sustaining such a high
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exercise intensity over several weeks is frequently associated with muscle pain and rapid
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27 exhaustion, and the suspension of the IATP.
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By designing a lightweight protocol including recovery bouts (IATP-R) we hypothesized to
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30 better fit with seniors’ capacities while enhancing maximal cardiorespiratory and endurance
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32 parameters. This has been investigated in a random way in sedentary seniors aged 70 or older.
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35 2. MATERIALS AND METHODS
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37 2.1. Study design
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The study was a prospective and open-label randomized controlled trial as specific exercise
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40 training program makes blind design very challenging4. It was conducted in the frame of the
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42 “Physical Aptitude Assessment for Health” consultation (CAPS in French language) of the
43 University Hospitals of Strasbourg (France). Using a computer-generated random numbers
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45 secure online platform (CleanWEB™), a methodologist of the Clinical Investigation Centre
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47 of the University Hospitals of Strasbourg independently assigned with 1:1 ratio sedentary
48 seniors to IATP-R or maintained sedentary lifestyle. The primary outcome was the first
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50 ventilatory threshold (VT1) and secondary were heart rate (HR) at baseline VT1, peak of
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oxygen uptake (VO2peak), maximal heart rate (HRmax), maximal tolerated power (MTP), and
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53 distance walked at the 6-minute walk test (6-MWT). The inclusion period was originally
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55 planned in the protocol over nearly three years (i.e., from December 2014 to October 2017).
56 However, the effective period of recruitment was finally limited to one year (i.e., from
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3 November 2016 to October 2017) because of logistical issues. The recruitment flow chart is
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detailed in figure 1.
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6 The local ethic committee had approved this experimental protocol (IDRCB: 2014-A00872-
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8 045/PRI: 2013-HUS; N°5830) which has been registered on ClinicalTrials.gov (Identifier:
9 NCT02263573).
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13 2.2. Population study and inclusion/non-inclusion criteria
14 Following a call of research subjects, seniors were invited to participate in this study with no
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16 financial incentives. A directed advertising edited in the local newspapers; and spread by
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radio as well as posters and flyers in local community centres, in general practitioners and
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19 physiotherapists’ offices, and in catering organizations for seniors was intended for
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21 prospective subjects. To be eligible, volunteers had to be aged 70 years or over and
22 functionally independent. They had to be sedentary (i.e., International Physical Activity
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24 Questionnaire score <2). Thus selected, volunteers completed a medical interview during
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which an electrocardiogram (ECG) and a full physical examination were carried out. During
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27 the physical examination, anthropometric parameters, resting HR, and blood pressure were
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recorded. Body height was measured by using an electronic height measure (Soehnle®); the
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30 body composition (i.e., total body weight, percentage of body fat, and fat-free mass) was
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32 analyzed with a bioelectrical impedance analysis (Tanita®, TBF-300) on morning after 8h of
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34 fasting, 48h after the last physical exercise, and after bladder voiding. The body mass index
35 was calculated as weight divided by height squared (kg/m²). According to present and past-
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37 medical history, the Charlson index13 was considered to define the burden of comorbidities
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(i.e., low (0≤score≤1), medium (2≤score≤4), or high level (≥5)) (Table 1). All conditions that
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40 contra-indicated IATP-R were then also identified (e.g., uncontrolled hypertension, current
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42 history of severe musculoskeletal and musculotendinous disorders, fibromyalgia, and un-
43 corrected visual impairment). In addition, individuals with significant cognitive impairment
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45 (i.e., delirium, amnestic disorders or dementia), undergoing chemotherapy for cancer, or
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47 suffering from any acute infection were not enrolled. Finally, all medications were reviewed
48 and listed, and participants taking beta-blockers and/or any other negative chronotropic drugs
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50 were not included. Were secondarily excluded all participants demonstrating chest pain, high
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blood pressure, rhythm disorder, ST segment deviation, and/or respiratory problems during
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53 the IET. During the medical interview, instructions about the IATP-R were provided and all
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55 participants had to sign the informed consent before final inclusion.
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3 2.3. The incremental exercise test (IET)
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In both study groups and blind to the participants’ group allocation, a cardiologist conducted
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6 an incremental maximal exercise tests (IET) at baseline and 9.5 weeks later (Figure 2). The
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8 IET were performed on an upright electronically braked cycle ergometer (Ergoselect 2,
9 MSE®) in the air-conditioned room (22.0±0.5°C), two hours after a light breakfast. Minute
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11 ventilation, O2 uptake and CO2 output were measured on a breath-by-breath basis by means of
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an open-circuit metabolic chart with rapid O2 and CO2 analyzers (MEDGRAPHICS, MSE®).
14 The pneumotachograph was calibrated with a 3-l calibration syringe, and the gas analyzers
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16 with reference gases. The breath-by-breath data were averaged over 20-second periods. HR
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was monitored continuously during the test with an ECG (T12, Mortara®). Each participant
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19 performed a maximal effort according to the criteria of the American Thoracic Society and
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21 the American College of Chest Physicians14 (i.e., predicted VሶO2peak achieved and/or a plateau
22 is observed; predicted MTP is achieved; predicted HRmax is achieved; peak exercise
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24 ventilation approaches or exceeds maximal ventilation capacity; respiratory exchange ratio
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26 ≥1.15; patient exhaustion/Borg Scale rating of 9–10 on a 0-to-10 scale) to determine MTP
27 (Watts – W), ܸሶ O2peak (L.min-1), maximal ventilation (ܸሶ E) (L.min-1) and HRmax (bpm). The
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VT1 (W) was determined graphically using the ܸሶ O2 (L.min-1), ܸሶ CO2 (L.min-1) and ܸሶ E (L.min-
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30 1
31 ) curves. It was confirmed by the method of Beaver et al.15 based on computerized regression
32 analysis of the ܸሶ CO2 versus ܸሶ O2 slopes. After a 3-min warm-up at 20 W, charge increments
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3 (22.0±0.5°C) of the CAPS. The IATP-R consisted of a 30-min cycling workout twice a week
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over 9.5-week (i.e., for 19 sessions). As depicted by figure 2, each session involved six 5-min
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6 bouts of exercise combining 4-min cycling at the measured pre-intervention VT1 workload
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8 (called “BASE”) and 1-min cycling at 40% of the pre-intervention VT1 workload (called
9 “RECOVERY”). All sessions started with 3-min warm-up and finished with a recovery period
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11 of 3-min. During exercise, HR was continuously recorded (Suunto T6c, Vantaa, Finland). The
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HR mean value was calculated every 3-min of each series of 4-min and taken as the “target
14 value” for the entire training program. When the exercise tolerance improved with training,
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16 for each HR decrease of 10 bpm a 10% increase in the ”BASE” was done, while the
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“RECOVERY” bouts values remained constant.
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21 2.6 Control group
22 For participants assigned to the control group, it was asked to maintain their current sedentary
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24 life style. This was controlled by phone call of the study investigator on a weekly basis during
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all the study period. Participants were then asked to confirm that they were not engaged in any
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27 specific exercise or training program since their inclusion. At the end of the study protocol,
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controls were offered to engage an IATP.
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32 2.7 Statistical analysis
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34 Statistical analyses were performed under Bayesian paradigm and computed with R (version
35 3.2.2) and WinBUGS (version 1.4.3) software. The sample size calculation was calculated for
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37 the primary outcome (VT1) and based on a between-time difference of 15 in the IATP-R
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group and 0 in the control group, and a between-time covariance of 15. The power was
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40 computed using simulations in a linear mixed model and was estimated to be 81%, with a type
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42 I error rate of 5%. The expected sample size was 130 overall (i.e., 65 per group). In the study
43 protocol, an interim analysis was originally planned when 60 participants were recruited (i.e.,
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45 30 in each group). According to the direction and magnitude of the results, the study could be
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47 then discontinued.
48 For the primary outcome, the intention to treat analysis was computed with a hierarchical
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50 model with fixed and random effect according to the following model: Yijk = β0 +
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β1×treatmenti + β2×timej + β3× (treatmenti×timej) + β4×subjectk + εijk. The effect of the
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53 intervention was estimated by the interaction term β3.
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55 For the secondary outcomes, in the intention to treat analyses, hierarchical Bayesian logistic
56 and linear regressions were considered according to the variable considered.
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For the descriptive analyses, results were expressed for numerical data as mean ± standard
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6 deviation; for categorical variables, number and percentage are presented. Normality of the
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8 distributions was tested using the Shapiro-Wilk, and was also assessed graphically using a
9 normal quintile plot. For the comparison of the participants’ characteristics at baseline,
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11 according to the study group, the credibility interval of β1 was used.
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For the computation, low informative prior probabilities (i.e., a β mean equal to 0 and its
14 variance equal to 1000) then more informative prior probabilities were considered for a
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16 sensibility analysis. For the posterior probability distributions, 95% credibility intervals were
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calculated and posterior probabilities of a difference given the data, written down P or
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19 probability, were given. This probability has not the same significance than the usual p-value
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21 (i.e., significant threshold). A probability >0.975 or <0.025 was considered as statistically
22 significant. In Bayesian paradigm there is no inflation of the alpha type I error with interim
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24 analyses.
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27 3. RESULTS
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The data presented resulted from the interim analysis. As planned in the experimental
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30 protocol, 60 volunteers (44 women; 16 men; mean age 73.8±3.2 years; age range: 70-83
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32 years) were enrolled. Their characteristics at baseline are detailed in Table 1 according to the
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34 allocated group. No difference was observed between the two groups in terms of
35 anthropometric parameters, main medical conditions and pre-intervention cardiorespiratory
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37 parameters.
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40 3.1 Adherence rate and adverse events
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42 Among participants, 56/60 successfully completed the study protocol (figure 1); withdrawals
43 in both groups were related neither to the training program nor to the sedentary period. In the
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45 IATP-R group, 27/30 volunteers have completed 19/19 training sessions; 2 participants 10/19
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47 and 5/19 sessions respectively; and 1 has left the training program after the consent form was
48 signed. With an adherence rate of 94.7% (defined as mean percentage of the exercise
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50 prescription), and with a total of 555 sessions, no adverse events or health problems directly
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attributable to the IATP-R were reported.
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55 3.2 Effects of the IATP-R
56 3.2.1 Maximal cardio-respiratory parameters
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3 Compared to controls, 88.9% of the IATP-R participants who have completed 19/19 sessions
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(n=27) have seen their cardiorespiratory parameters improved during the final IET; 11.1%
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6 remained stable in their performance level. Globally, all parameters were improved (MTP:
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8 +19.2% vs. -2.3%; VO2peak: +14.1% vs. -2.7%; and HRmax: +1.6% vs. -1.7%) compared to
9 controls (Figure 3 and Table 2). With respect to MMV values no difference was measured
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11 between the 2 groups and between final and baseline IET within each group.
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14 3.2.2 Endurance parameters
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16 Compared to controls, among the IATP-R volunteers who have completed 19/19 sessions
17 (n=27), 81.5% have seen their endurance parameters improved during the final IET; 18.5%
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19 remained stable. Compared to controls, all endurance parameters were improved (VT1:
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+18.3% vs. -4.6%; HR at baseline VT1: -6.0% vs. +1.5% and distance walked at 6-MWT:
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22 +11.6% vs. -3.1%) (Figure 3 and Table 2).
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4. DISCUSSION
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27 This study aim was to measure the benefit, safety and acceptability of an IATP-R in sedentary
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seniors. After only 9.5 weeks of training, in addition to reporting significant improvements in
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30 maximal cardiorespiratory and endurance parameters, this study demonstrated the good
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32 adherence rate and safety of the IATP-R. These findings resulted from an interim analysis
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leading to premature discontinuation of the study. In order to make easier comparisons with
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35 previous reports and similar studies, the effects of the IATP-R have been presented as
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37 percentage of change instead of absolute values20.
38 To the best of our knowledge, this is the first randomized trial that provides evidence of the
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40 effectiveness, safety and feasibility of IATP-R in seniors. Commonly, a training program is
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42 considered as feasible when the adherence rate is >75%21. The great adherence rate reported
43 with IATP-R was much higher than those usually reported with common IATP22-25. It was
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45 explained by the design of the program that was supervised and personalized. These criteria
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are known to be more effective in reducing the risk of injury and in improving performance
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48 among seniors compared to home-based or un-supervised programs26. In addition, the active
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50 recovery bouts corresponding to periods of sub-lactate threshold work rates have probably
51 facilitated the lactate removal27 and hence reduced the associated-fatigue. They also
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53 contributed to increase the exercise tolerance and finally the program acceptability28.
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55 Regarding endurance parameters, the improvement associated with IATP-R is of great
56 importance and specifically for seniors. Indeed, seniors perform their everyday activities at an
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3 intensity level that corresponds to that of VT1 rather than to that of VO2peak10. Additionally,
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since the VT1 is a direct and objective readout of cardiopulmonary capacity, the intensity of
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6 the exercise was determined individually according to physical capacity. This was
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8 independent of the patient’s motivation29. Thus, this study reported an improvement in VT1 by
9 18.3% which was nearly of similar amplitude to the 20.0 and 21.5% improvement reported by
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11 Vogel et al.10 and Beale et al.22 respectively. Likewise, we measured a significant decrease of
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6% in HR at baseline VT1 after the IATP-R, which is similar to that observed in Vogel et al.10
14 with IATP. Moreover, IATP-R significantly improved the distance walked at the 6-MWT by
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16 56 meters (+11.6%). This result is in line of previous reports30,31.
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Globally, in spite of a reduced total volume of physical activity, IATP-R induced also
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19 enhancement in aerobic capacities of similar extends to which previously reported with
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21 common IATP. Thus, in seniors, Coker et al.32, Foster et al.33, Perini et al.24, and Vogel et
22 al.10 reported a significant improvement in VO2peak of 14 to 17% after 9 to 12-week of IATP.
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24 This magnitude of VO2peak enhancement was also similar to those measured after medium-
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(i.e., 14-24 weeks)34,35 and long-term (i.e., >24 weeks)36 AT programs. Thus, Lovell et al.34
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27 and Villareal et al.35 demonstrated a significant increase by 15.0 and 18.7% after 16 and
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24week of AT. After 24-week, the VO2peak enhancement reported by Evans et al.36 was of
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30 15.0%. Well beyond the exact magnitude of the improvement, VO2peak values must be also
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32 interpreted in the light of what exercise capacity represents exactly in seniors. Indeed, several
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34 studies have reported an accelerated rate of decline in VO2peak per decade after the 7th decade
35 (i.e., 20 vs. 10% for the global population). Thus, although for most healthy adults VO2peak has
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37 little bearing on everyday life, for sedentary seniors, perform some activities of daily living
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becomes greatly dependent on VO2peak37. Furthermore, VO2peak is also considered as the most
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40 powerful predictor of mortality compared to other well-established risk factors4. Every 3.5
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42 ml/kg/min increase in VO2peak has been associated with a 12% extension in overall survival38.
43 The median absolute gain in VO2peak measured in the present study was 3.4 ml/kg/min.
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45 Three main reasons can explain the benefits of the IATP-R. The first one was the personalized
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47 design of the program according to the VT1 value obtained during the baseline IET. Thus, the
48 intensity of the IATP-R was adjusted to the real capacities of each volunteer. Second, session
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50 after session the workload of the “BASE” was adapted according the evolution of the HR.
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Thus, the exercise workload and intensity were adjusted according to the progress of the
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53 participant. The third reason was the interval rather than continuous design of the program.
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55 Indeed as reported in the literature39, this has contributed to the benefits measured in terms of
56 cardiorespiratory and endurance parameters in this sedentary senior’s population. In middle-
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3 aged populations, IATP is definitely the optimal design to maximize peripheral muscle and
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central cardiorespiratory adaptation whereas continuous is only associated with greater O2
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6 extraction8,9. Specifically, it has been established that when muscle work increases through
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8 IATP, the oxidative pathway is challenged8,9. Lactate accumulation is then reduced through
9 oxidative phosphorylation during the low intensity period intervals. The decrease in blood
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11 lactate induced by training led also to slowing down the glycogen breakdown that in turn
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favors a more efficient oxidative pathway40. Thus, by inducing greater central and peripheral
14 adaptations, IATP is significantly more efficient than continuous in improving aerobic
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16 capacity in seniors10. With a similar volume of physical activity, IATP results in lower HR,
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VO2 consumption, ventilation and blood lactate O2 uptake compared to continuous.
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19 Moreover, IATP is better tolerated than continuous39.
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21 This study has also some limitations. First, the sample size is relatively modest. However, it
22 was apparently enough powerful to measure a significant improvement in endurance and
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24 cardiorespiratory capacities. But the generalization of the results is restricted by the voluntary-
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based recruitment and the healthy status of the volunteers whilst sedentary and aged. Finally,
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27 the study sample was also small to analyze any effect of gender.
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30 5. PERSPECTIVE
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This study demonstrates that the IATP-R enhances maximal cardiorespiratory and endurance
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33 parameters in addition to be safe and feasible in sedentary seniors. However, potential
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35 benefits on functional and cognitive performances, and cardiovascular risk factors have still to
36 be addressed in similar and in less healthy aged populations with specific age-associated
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38 chronic conditions.
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41 ACKNOWLEDGEMENTS
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43 We would like to thank the study participants for taking part in this trial. We are also grateful
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to Cecile Dufour, Julien Bahlau, and Cedric Momas for their technical support in writing this
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46 manuscript and Richard Medeiros and Katherine Jumel for their editorial assistance.
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49 Funding information
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51 This study was funded by the Department of Clinical Research and Innovation of the
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University Hospitals of Strasbourg.
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3 Conflicts of Interest
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The authors declare that they have no competing interests regarding the publication of this
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6 article.
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9 Trial registration
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11 ClinicalTrials.gov NCT02263573. Registered October 1, 2014.
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3 Figure Captions
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Figure 1: Flow chart of the study
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6 Note: IATP-R: interval aerobic training program with recovery bouts; IATP: interval aerobic training program
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9 Figure 2: Protocol design of the study
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Note: VT1: first ventilatory threshold; IET: incremental exercise test; IATP-R: interval aerobic training program
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12 with recovery bouts; 6-MWT: 6-minute walk test; IATP: interval aerobic training program
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15 Figure 3: Box plot of maximal cardio-respiratory and endurance parameters in control and
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17 training groups before and after the study
18 Note: CG: control group, TG: training group, VO2peak: peak of oxygen uptake, HRmax: maximal heart rate, MTP:
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maximal tolerated power, VT1: first ventilatory threshold, HR: heart rate, 6-MWT: 6-minute walk test
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3 Table 1: Baseline characteristics of the 60 study subjects presented according to the study group
4 Control group IATP-R group
5 Subjects’ characteristics
N = 30 N = 30
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7 Age (years ± SD) 74.3 ± 3.4 72.9 ± 2.5
8 Female, n (%) 23 (76.6) 21 (70.0)
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Anthropometric parameters
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11 Weight (kg ± SD) 77.8 ± 13.9 77.4 ± 15.4
12 Body fat (kg ± SD) 37.6 ± 8.3 35.1 ± 8.4
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Free-fat mass (kg ± SD) 46.0 ± 6.7 47.0 ± 9.2
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Body mass index (BMI – kg/m ± SD) 28.8 ± 5.1 28.7 ± 5.6
16 Normal weight (18.5 ≤ BMI ≤ 24.9), n (%) 6 (20.0) 7 (23.3)
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Overweight (25.0 ≤ BMI ≤ 29.9), n (%) 12 (40.0) 10 (33.3)
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19 Obesity (30.0 ≤ BMI ≤ 40.0), n (%) 12 (40.0) 13 (43.3)
20 Main medical conditions
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22 Charlson Comorbidity Index (mean ± SD) 3.8 ± 1.3 4.0 ± 1.7
23 Hypertension, n (%) 11 (36.7) 12 (40.0)
24 Diabetes mellitus type 2, n (%) 3 (10.0) 6 (20.0)
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30 Osteoarthritis, n (%) 4 (13.3) 3 (10.0)
31 Depression, n (%) 2 (6.6) 4 (13.3)
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Smoking, n (%) 1 (3.3) 1 (3.3)
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3 Table 2: Effects of IATP-R on maximal cardio-respiratory and endurance parameters
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β3 95% CI Probability (%)
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6 Endurance parameters
VT1 14.65 9.06 ; 20.19 99.99
7 HR at baseline VT1 -8.37 -11.82 ; -4.99 00.00
8 6-MWT 73.84 57.62 ; 89.60 99.99
9 Maximal cardiorespiratory parameters
10 VO2peak 3.33 2.0 ; 4.65 99.99
11 HRmax 5.81 1.85 ; 9.80 99.70
12 MTP 22.08 15.31 ; 28.82 99.99
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Note: Significance of the results is expressed as probability (%). The result is considered as significant when the probability
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15 is close to 100% or 0%.
16 β3: interaction term, CI: credibility interval, VT1: first ventilatory threshold, HR: heart rate, 6-MWT: 6-minute walk test,
17 VO2peak: peak of oxygen uptake, HRmax: maximal heart rate, MTP: maximal tolerated power
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