Effects of Breaking up Sitting Time on Cardiometabolic Risk Markers and Cardiac Function Post Myocardial Infarction
Phase: NA
Conditions: Cardiovascular Diseases
Sponsor: University of Bedfordshire

 
1 
Effects of breaking up sitting time on cardiometabolic risk markers and cardiac 
function post myocardial infarction.  
 
SHORT STUDY TITLE / ACRONYM 
The MOVE-MI study  
 
PROTOCOL VERSION NUMBER AND DATE 
V6.0/ 12May20 
RESEARCH REFERENCE NUMBERS 
 
IRAS Number: 
265468 
SPONSORS Number: 
N/A 
 
 
 

 
2 
SIGNATURE PAGE 
The undersigned confirm that the following protocol has been agreed and accepted and that 
the Chief Investigator agrees to conduct the study in compliance with the approved protocol 
and will adhere to the principles outlined in the Declaration of Helsinki, the Sponsor’s SOPs, 
and other regulatory requirement. 
I agree to ensure that the confidential information contained in this document will not be used 
for any other purpose other than the evaluation or conduct of the investigation without the prior 
written consent of the Sponsor 
I also confirm that I will make the findings of the study publically available through publication 
or other dissemination tools without any unnecessary delay and that an honest accurate and 
transparent account of the study will be given; and that any discrepancies from the study as 
planned in this protocol will be explained. 
 
For and on behalf of the Study Sponsor: 
Signature:  
...................................................................................................... 
 
Date: 
....../....../...... 
Name (please print): 
...................................................................................................... 
 
 
Position: 
...................................................................................................... 
 
 
Chief Investigator: 
Signature: 
...................................................................................................... 
 
Date: 
....../....../...... 
Name: (please print): 
......................................................................................................
 
 
 
 

 
3 
 
LIST of CONTENTS 
GENERAL INFORMATION 
Page No. 
HRA PROTOCOL COMPLIANCE DECLARATION  
2 
TITLE PAGE  
1 
RESEARCH REFERENCE NUMBERS 
 
1 
SIGNATURE PAGE 
2 
LIST OF CONTENTS  
3 
KEY STUDY CONTACTS 
5 
STUDY SUMMARY 
6 
FUNDING 
 
7 
ROLE OF SPONSOR AND FUNDER 
7 
ROLES & RESPONSIBILITIES OF STUDY STEERING 
GROUPS AND INDIVIDUALS  
 
7 
STUDY FLOW CHART 
 
9 
SECTION  
1. BACKGROUND 
 
10 
2. RATIONALE 
 
13 
3. THEORETICAL FRAMEWORK 
13 
4. RESEARCH QUESTION/AIM(S)  
13 
5. STUDY DESIGN/METHODS 
14 

 
4 
6. STUDY SETTING 
18 
7. SAMPLE AND RECRUITMENT 
18 
8. ETHICAL AND REGULATORY COMPLIANCE 
20 
9. DISSEMINATION  POLICY 
25 
10. REFERENCES 
26 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
5 
 
KEY STUDY CONTACTS 
Chief Investigator 
Dr Joanna Richards 
Institute for Sport and Physical Activity Research 
University of Bedfordshire 
Polhill Avenue 
Bedford 
MK41 9EA 
Email: jo.richards@beds.ac.uk 
Study Co-ordinator 
Abbie Bell 
PhD Student  
Institute for Sport and Physical Activity Research 
University of Bedfordshire 
Polhill Avenue 
Bedford 
MK41 9EA 
Tel: 07984545911 
Email: abbie.Bell@study.beds.ac.uk 
Sponsor 
University of Bedfordshire 
Polhill Avenue 
Bedford 
MK41 9EA 
Funder(s) 
N/A 
Key Protocol Contributors 
Abbie Bell, PhD Student  
Institute for Sport and Physical Activity Research 
abbie.Bell@study.beds.ac.uk 

 
6 
Committees 
N/A 
 
 
 
STUDY SUMMARY 
Study Title 
Effect of breaking up sitting time on cardiometabolic risk 
markers and cardiac function post myocardial infarction. 
Internal ref. no. (or short title) 
The MOVE-MI study 
Study Design 
Randomised, cross-over trial 
Study Participants 
Low risk patients with a first uncomplicated myocardial 
infarction 
Planned Size of Sample (if applicable) 23 participants 
Follow up duration (if applicable) 
N/A 
Planned Study Period 
1 year 
Research Question/Aim(s) 
Does breaking up sitting time in patients following a 
myocardial infarction improve their cardiometabolic risk 
markers and cardiac function? 
 
 
 
 
 
 
 
 
 
 

 
7 
ROLE OF STUDY SPONSOR AND FUNDER 
The Sponsor of this study is the University of Bedfordshire. The sponsor is responsible for the 
overall conduct and management of the study  
There is no external funder for this study. 
 
ROLES AND RESPONSIBILITIES OF STUDY MANAGEMENT COMMITEES/GROUPS & 
INDIVIDUALS 
Cardiac Rehabilitation Team at Bedford Hospital 
Regular meetings will be held between the Bedford Hospital Cardiac Rehabilitation team and 
the study investigators to discuss how to conduct the study in terms of participant recruitment, 
data collection and dissemination.  
 
Patient and Public Involvement 
Prior to the commencement of the study, a PPI group study session will be held with post MI 
patients to discuss the study design and coordination. This will help the research team to 
understand any difficulties with recruitment that they may face, as well as how best to conduct 
the study. Here, they will also be shown any patient facing documents to ensure they are 
suitably aimed at the target population.  
 
 

 
8 
PROTOCOL CONTRIBUTORS 
Abbie Bell 
PhD Student  
Institute for Sport and Physical Activity Research 
Responsibilities: Study design, study conduct, data analysis and interpretation, manuscript 
writing, and dissemination of results. 
 
Dr Joanna Richards 
Director of Studies 
Institute for Sport and Physical Activity Research 
Responsibilities: Overview of study design, conduct, data analysis and interpretation, 
manuscript writing, and dissemination of results 
 
Dr Daniel Bailey 
Second supervisor 
Institute for Sport and Physical Activity Research 
Responsibilities: Overview of study design, conduct, data analysis and interpretation, 
manuscript writing, and dissemination of results.  
 
KEY WORDS: 
Post- myocardial infarction (post-MI), Cardiac Rehabilitation 
(CR), sedentary behavior, cardiometabolic risk 
 
 
 
 
 
 
  

 
9 
STUDY FLOWCHART 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Identification  
Discussion with cardiac 
rehabilitation team for eligible 
patients (ST or non-ST elevated 
myocardial infarction)  
Study Discussion   
Eligible patients approached by 
research team following phase 
II CR appointment to discuss 
study. 
Consent to contact form given    
Contact with patient 24 to 48 hours 
after initial CR appointment?    
Patient called to discuss study 
participation and arrange first 
study visit.  
If patient is interested in taking part 
in the study 
If patient is not interested in taking 
part in the study 
No further contact with the patient 
will be made  
Visit 1 – Preliminary testing visit   
Height, weight and waist 
circumference measured 
Familiarisation with stepping to 
metronome 
Visit 2 – Intervention   
Visit 3 – Intervention   
Visit 4 – Intervention   
Complete following conditions in 
random order: 
 
Condition 1: Uninterrupted sitting. 
 
Condition 2: Breaking up sitting 
every 30 min with 5 min of 
standing. 
 
Condition 3: Breaking up sitting 
every 30 min with 5 min of light 
intensity stepping. 

 
10 
STUDY PROTOCOL 
 
1 BACKGROUND 
Cardiovascular Disease (CVD) is the leading causes of mortality and morbidity globally (World 
Health Organization, 2019). In the UK alone, it was accountable for 124,641 deaths in 2017. 
Further to this, CVD contributes to a vast economic burden, costing the National Health 
Service (NHS) £19 billion annually. This is mainly due to a significant number of hospital 
readmissions following a first cardiac event (198,000 per annum) (British Heart Foundation, 
2018).  
Following a myocardial infarction (MI), an individual is at an increased risk of a secondary 
event (20-50% higher risk post MI), compared to those with no prior CVD (Kerr, et al., 2009). 
Guidelines therefore recommend close management of cardiometabolic risk markers to 
reduce the risk of a secondary event, with a particular focus on lipid profile and glucose control 
(European Society of Cardiology, 2019). Poor metabolic health (including impaired lipid and 
glucose metabolism and high blood pressure levels) is strongly associated with CVD.  In turn, 
there is an increase in insulin resistance and pro-atherogenic markers within the blood that 
causes endothelial dysfunction. This contributes to the progression of atherosclerosis and thus 
increases the risk of CVD (Dimina and Mariotti, 2019; Oikonomou, et a., 2019).  
There is a linear relationship between both fasting and 2 hour glucose levels with CVD, 
independent of insulin resistance and type 2 diabetes mellitus (T2DM) (Ning, et al., 2010). A 
meta-analysis found that, after adjusting for other cardiovascular risk factors, higher blood 
glucose (both fasting and 2 hour) was positively correlated to the development of CVD, thus 
suggesting that the more poorly glucose was controlled, the more likely an individual is to 
develop CVD. Further to this, both triglycerides and blood pressure (BP) showed a likewise 
association with CVD (Ning, et al., 2010). It is therefore essential to appropriately manage 
these cardiometabolic risk markers to reduce the risk of secondary cardiovascular events 
occurring.  
Cardiac Rehabilitation (CR) is a secondary preventative measure to further cardiac events. 
The British Association of Cardiovascular Prevention and Rehabilitation (BACPR) defines CR 
as ‘the coordinated sum of activities required to influence favourably the underlying cause of 
cardiovascular disease, as well as to provide the best possible physical, mental and social 
conditions, so that the patients may, by their own efforts, preserve or resume optimal 
functioning in their community and through improved health behaviour, slow or reverse 
progression of disease’. It is suggested by the National Institute for Health and Care 

 
11 
Excellence (NICE) that all patients should be offered a CR programme with an exercise 
component following an MI (BACPR., 2017).  
There is conflicting evidence regarding the benefits of exercise based CR upon cardiovascular 
mortality and morbidity, hospital readmissions and all-cause mortality. Previously, CR has 
been shown to be beneficial in longer term health outcomes of cardiac patients. The 2016 
Cochrane Review of Exercise based CR found that, when compared with a no exercise control 
group, exercise based CR accounts for an estimated risk reduction of 26% and 18% for 
cardiovascular mortality and hospital admissions respectively, but no reduction in total 
mortality or further cardiovascular events (Anderson, et al., 2016).  
However, delivery and structure of CR programmes vary significantly across the country. The 
British Association for Cardiovascular Prevention and Rehabilitation (BACPR) recommends 
that ‘the patient should receive individual guidance and advice on active daily living together 
with a tailored activity and exercise plan with the collective aim to increase physical fitness, as 
well as overall daily energy expenditure and decrease sedentary behaviour’ (BACPR, 2017). 
Despite recommendations to reduce sedentary behaviour, suggestions on how to do so are 
currently non-existent. Sedentary behaviour is defined as a waking energy expenditure of £1.5 
METs (metabolic task equivalent) while in a seated, reclined or lying posture (Tremblay, et al., 
2017). Independent of physical activity levels, high amounts of daily sitting is a risk factor for 
CVD (Bailey et al., 2019)).  
Studies show that breaking up sitting time can reduce cardiometabolic risk markers, thus 
reducing CVD risk. Within the US National Health and Nutrition Examination Survey 
(NHANES) study, a detrimental linear association was found between total time spent sitting 
and waist circumference, high density lipoprotein cholesterol (HDL-C), triglycerides, insulin, 
insulin sensitivity and b cell function. In addition, independent of total sitting time, a higher 
number of breaks in sitting per day was significantly beneficially associated with waist 
circumference, C-reactive protein and fasting plasma glucose. Therefore, both reducing total 
sitting time and frequently breaking up prolonged periods of sitting are associated with 
improved cardiometabolic risk in the general population (Healy, et al., 2011).  
There is consistent evidence to suggest that breaking up sitting time with 2-5 minutes of light 
or moderate intensity walking every 20-30 minutes reduces postprandial glucose (Benatti et 
al., 2015).  For example, a randomized cross-over design study conducted by Bailey and 
Locke (2015) found that breaking up sitting with 2 minutes of light physical activity every 20 
minutes reduced postprandial glucose by 16%, but breaking up prolonged sitting with 2 
minutes of standing every 20 minutes did not. In participants with impaired metabolic health 
(e.g. overweight/obese, impaired glycaemia, and people with T2DM), findings have shown 

 
12 
that breaking up sitting time with both standing and light physical activity have benefits on 
postprandial cardiometabolic risk markers (including blood pressure, glucose, insulin and 
triglycerides) (Henson et al., 2016; Dempsey et al., 2016). For instance, a study in 
dysglycaemic, overweight, postmenopausal women found that breaking up sitting time with 5 
minutes of standing every 30 minutes resulted in a 34% reduction in postprandial glucose 
incremental area under the curve (iAUC). Breaking up sitting with 5 minutes of light-intensity 
self-paced walking (10-12 on the Borg Rating of Perceived Exertion [RPE] scale) every 30 
minutes resulted in a 28% reduction in glucose iAUC. Similar effects were seen for insulin 
iAUC, which was reduced by 20% with standing breaks and 37% by light intensity walking 
breaks (Henson, et al., 2016). In patients with T2DM, improvements in postprandial 
cardiometabolic risk markers (glucose, insulin and triglycerides) were seen when sitting was 
interrupted with light intensity walking (3 minutes every 30 minutes) and simple resistance 
exercises (3 minutes every 30 minutes). Overall, there was a reduction in postprandial glucose 
iAUC of 39% in both conditions and postprandial insulin iAUC by 36% and 37% in the light-
intensity walking condition and resistance activities conditions, respectively. Postprandial 
triglycerides were also significantly attenuated in the simple resistance activities condition, but 
not in response to light-intensity walking breaks. Light-intensity walking and resistance 
exercise breaks also resulted in a significant reduction in systolic and diastolic blood pressure 
(Dempsey, et al., 2016).  To our knowledge, there have been no studies conducted to date 
evaluating the effects of breaking up prolonged sitting on cardiometabolic risk markers in 
cardiac patients. 
In addition to poor cardiometabolic health following an MI, an individual can develop structural 
problems within the myocardium due to myocardial damage and necrosis (Thygesen, et al., 
2007). If not managed appropriately, this causes left ventricular (LV) hypertrophy and reduced 
LV ejection fraction, thus resulting in LV remodeling (Azvedo, et al., 2016). This leads to poor 
prognostic outcomes for the individual, ultimately resulting in chronic heart failure. This can 
include shortness of breath, decline in functional capacity and difficulty with active daily living 
tasks, as well as mental health problems and poor health related quality of life (Lesman-
Leegte, et al., 2009). Therefore, interventions need to be identified to prevent these myocardial 
changes following an MI.  
Data from the Bogalusa Heart study suggests that individuals with metabolic syndrome had 
significantly higher values for LV mass, end-diastolic posterior wall thickness, septal wall 
thickness and LV end diastolic diameter (Patel et al., 2009). Further to this, high blood 
pressure, high fasting glucose, high triglycerides and low HDL-C are independently associated 
with eccentric hypertrophy of the LV. As breaking up sitting time can acutely improve 
cardiometabolic risk markers, it is plausible that there could be benefits to cardiac function as 

 
13 
well. This would be of great importance to cardiac patients who are at high risk of suffering a 
secondary event and thus requires evaluation.  
 
2 
RATIONALE  
While there is extensive research into the effects of exercise based CR upon secondary health 
outcomes, little is known regarding the effects of breaking up sitting time on cardiometabolic 
risk markers or cardiac function in individuals that have suffered a cardiac event. Despite 
BACPR recommending to reduce sedentary behaviour within this population, CR programmes 
are vague when addressing this health behavior and evidence does not exist to appropriately 
inform programmes in this respect. In healthy, overweight/obese and Type 2 diabetic 
individuals, it is known that breaking up sitting time acutely improves postprandial 
cardiometabolic risk markers.  However, no research has evaluated the effects of breaking up 
sitting time on these biomarkers or cardiac function in individuals who have suffered a cardiac 
event.  
 
3 
THEORETICAL FRAMEWORK 
Regularly attending CR significantly improves health outcomes following a cardiac event. 
BACPR recommends that ‘the patient should receive individual guidance and advice on active 
daily living together with a tailored activity and exercise plan with the collective aim to increase 
physical fitness, as well as overall daily energy expenditure and decrease sedentary 
behaviour’ following a cardiac event. However, little is known regarding the effects of breaking 
up sitting time on cardiometabolic risk markers in this population. In healthy individuals and 
those with impaired metabolic health, breaking up sitting time results in favourable reductions 
in cardiometabolic risk markers over a single day. It can therefore be hypothesised that 
breaking up sitting in cardiac patients will reduce cardiometabolic risk markers and thus 
contribute to a reduced risk of a secondary cardiovascular event. 
 
4 
RESEARCH QUESTION/AIM(S) 
1) What are the effects of breaking up sitting time on cardiometabolic risk markers and cardiac 
function in patients following a myocardial infarction?  
 
4.1 
Objectives 

 
14 
To determine whether breaking up sitting time with standing or light physical activity acutely 
improves cardiometabolic risk markers and cardiac function in individuals who have suffered 
a myocardial infarction.  
 
4.2 
Outcome 
The primary outcome of this study is postprandial glucose. Other outcome measures include: 
(i) cardiometabolic risk markers: postprandial triglycerides, high density lipoprotein cholesterol 
(HDL-C), c-reactive protein, insulin, and blood pressure (ii) cardiac function: global longitudinal 
strain (%), stroke volume (L) and ejection fraction (%), and (iii) mood and wellbeing. 
 
5 
STUDY DESIGN and METHODS of DATA COLLECTION AND DATA ANALYSIS 
Study design 
A repeated measures, randomised cross over study design will be used. All data collection 
will take place at the Sport and Exercise Science Laboratories, University of Bedfordshire, 
Polhill Avenue, Bedford, UK. After a preliminary testing session, participants will complete 
three, 6-hour experimental conditions in a random order: 1) uninterrupted sitting; 2) sitting 
interrupted with standing breaks, and 3) sitting interrupted with light intensity stepping breaks. 
There will be a washout period of at least 72 hours between conditions, as previous research 
suggests that a single session of exercise can affect blood glucose levels for the following 48 
hours (Mikines, et al., 1988). Participants will be randomised to order of condition using 
computer generated random numbers. This will assign them a trial order using block 
randomization with balanced block sizes. Participants will be blinded to the trial condition until 
they arrive on the day of their first and second experimental conditions.  
 
Preliminary testing 
Patients will first attend a preliminary testing session where they will become accustomed to 
light intensity stepping on the spot to the beat of a metronome and use of the Borg RPE scale. 
This will ensure patients are familiar with an intensity that is equivalent to an RPE of 8-11 (very 
light to light) that will be used in the respective experimental condition. Participants will step 
to different metronome paces starting at a slow pace and building up gradually every 1-2 
minutes until an RPE of 8-11 is found. This imitates the intensity recommended within the 
warm up of CR, as recommended by BACPR. Height (cm) and weight (kg) will also be 
measured using a stadiometer (Harpenden 98.602, Holtain Ltd., Crymych) and digital scales 

 
15 
(Tanita BWB0800, Tanita Corp., Tokyo, Japan) respectively, to calculate body mass index 
(kg/m2).  
 
Experimental Protocol 
Participants will be asked to refrain from any alcohol and caffeine for 24 hours prior to each 
visit, as well as avoid exercise for 72 hours and complete an overnight fast. This will be 
explained to them during the preliminary visit. To monitor this, they will be asked prior to 
participation per visit whether they have fasted/ when they last ate and drank.  
Participants will be asked to perform an overnight fast for at least 10 hours before arrival and 
minimise active travel to the laboratory (e.g. use a car for travel). They will rest for 30 minutes 
to achieve a steady state before baseline blood pressure (two measures with 2 minutes rest 
between each and the average taken) and blood samples are taken. Baseline cardiac function 
measures (global strain, ejection fraction and systolic volume) will be measured using an 
echocardiogram scan, as well as an electrocardiogram (ECG) to ensure there are no electrical 
contraindications to the heart which would make the participant unsuitable to complete the 
study intervention including ST depression / elevation or any arrythmias. Baseline mood and 
wellbeing measures will then be assessed using questionnaires.  
 
Following baseline measures, a standardised breakfast will be consumed (see meals section 
below) and participants will then commence the experimental condition. See Figure 1 for 
schematic of experimental conditions.  
 
The three experimental conditions for this study are: 
1) Uninterrupted sitting for 6 hours.  
2) Sitting interrupted with 5 minutes of static standing every 30 minutes.  
3) Sitting interrupted with 5 minutes of light intensity stepping every 30 minutes using a 
metronome at the intensity determined during preliminary testing. This replicates active 
recovery time currently performed in a phase III CR class.  
 
A lunch meal will be provided at 12:00 during each condition. During sitting periods, 
participants will be able to read books, magazines or newspapers and/or watch TV, DVDs or 
media streaming services. Participants will be transported to the toilets and food consumption 
areas using a wheelchair to ensure activity is minimised and standardised between conditions. 
 
Standardised food and water intake 

 
16 
Each meal will provide approximately 30% of estimated daily energy requirements. This will 
be calculated for each individual participant using a prediction equation based on individual’s 
height, weight and gender. Breakfast will consist of bran flakes, whole milk, and a honey and 
granola bar and will consist of 54% carbohydrate, 34% fat and 12% protein. Lunch will consist 
of a chicken sandwich, salted crisps and jammie dodger biscuit (54% carbohydrate, 34% fat 
and 12% protein). The macronutrient composition of the meals are in general agreement with 
guidelines recommended for a balanced diet (Public Health England, 2016). Participants will 
be encouraged to consume their meal within 15 minutes. The time taken will be recorded in 
the first condition and this time will then be replicated in the latter two conditions. Water will 
be available for the participants ad libitum during their first experimental condition visit. This 
volume of intake will be recorded and the same amount provided in the following two 
conditions spread over the day.  
 
 
Data collection 
Finger prick capillary whole blood samples will be collected at baseline, 30, 60, 120, 180, 210, 
240, 300 and 360 minutes throughout the conditions to allow later analysis of glucose, 
triglycerides, HDL-C, and insulin. Blood samples will be taken after the hand is pre-warmed in 
warm water for approximately 5 minutes. Blood pressure and heart rate will be measured 5 
minutes before each of the blood samples are taken. Cardiac function measures and mood 
and wellbeing will be measured at baseline and post-condition 
 
  
 
Figure 1: Schematic of experimental protocol, PA, physical activity;  ECG, electrocardiogram.  
 
 

 
17 
 
Biochemical analyses 
600µl of whole capillary blood will be collected using EDTA microvette tubes that will be 
centrifuged (Heraeus Pico 17 microcentrifuge; Thermo Scientific, Loughborough, UK) at 2000 
× g for 5 min. The plasma will then be pipetted into 0.5 mL eppendorf tubes and stored at -80° 
for later analysis. Plasma glucose and triglyceride concentrations will be analysed via 
enzymatic colorimetric methods using a benchtop analyser (Pentra 400; HORIBA ABX 
Diagnostics, Montpellier, France). Plasma insulin concentrations will be determined using an 
enzyme linked immunosorbent assay technique (Mercodia, Uppsala Sweden).  
 
 
Blood pressure and heart rate 
Blood pressure and heart rate will be measured in an upright, seated position using an 
automated device (Omron M5-1 automated oscillatory device, Omron Matsusaka Co. Ltd., 
Matsusaka, Japan). The same arm will be used for BP measurement each time throughout 
the study, which will be taken on the left arm unless there is preference for the right arm due 
to any potential previous medical conditions. A single measure will be taken at each time point 
apart from baseline where two measures will be taken with a 2 minute rest between each. 
 
Cardiac function 
In a laboratory, the patient will be asked to undress from the waist up and lay on the medical 
couch in the left lateral decubitus position. Here, a scanning gel will be applied to the 
echocardiogram probe. This forms part of the echocardiogram system; Vivid 7, GE Medical, 
Mius Ltd., Gloucester, UK). Parasternal and apical views will be acquired (Armstrong and 
Ryan., 2012). Once these images are collected and stored, the gel will be removed from the 
probe and chest. All images will be stored anonymously, where participants will be given a 
participant ID number. All image analysis will be completed using Echopac software (GE 
Healthcare, Version 113, GE healthcare, Chicago, Illinois, United States). 
LV mass, LV mass index (adjusted for height), LV end diastolic volume, LV end systolic 
volume, wall motion score index (WMSI), E/A ratio, relative wall thickness, and deceleration 
time will be measured. These measures will be used to calculate left ventricular function.  
 
Mood and wellbeing 
The Positive and Negative Affect Scale (PANAS) questionnaire (Watson et al., 1988) will be 
used to assess current mood and subjective wellbeing measured using the National Wellbeing 
Measurement. These questionnaires will be completed at baseline and immediately after 

 
18 
cardiac function measures post-condition. There is a significant correlation post cardiac event 
and poor mental health (Chadda, et al., 2016). This questionnaire will therefore measure 
whether breaking up sitting time regularly within this population will improve mental health 
measures. PANAS is a valid questionnaire, which can be modified to measure changes in 
mood across a day, without losing its validity (Watson, et al., 1988). If incidental findings of 
anxiety or depression occur, the GP shall be informed via a letter sent directly to them.  
 
Data analyses 
Statistical analyses will be conducted using SPSS Version 23 (IBM, Armonk, NY, USA). 
Postprandial glucose, insulin, triglycerides, HDL-C, SBP and DBP iAUC will be calculated for 
each condition using the trapezoidal rule. Mean arterial blood pressure will be calculated as: 
MAP@ PDiastolic blood pressure + 
!
" (Psystolic blood pressure - Pdiastolic blood pressure). Normality of the data will be 
checked using quantile-quantile plots. Linear mixed models will be used to compare the 
dependent variables between conditions. Fixed factors for each model will be condition and 
fasting outcome variable values (as covariates) and participants will be entered as a random 
factor. Post-hoc analyses will be conducted use the Sidak adjustment if a significant main 
effect of condition is present. Cohen’s d effect sizes will be calculated to describe the 
magnitude of differences between conditions. Data will be presented as a mean (95% CI). 
Significance will be set at p<0.05.  
 
6 
STUDY SETTING 
All testing will take place at the University of Bedfordshire Sport and Exercise Science 
Laboratories. 
 
7 
SAMPLE AND RECRUITMENT 
7.1  
Eligibility Criteria 
7.1.1 Inclusion criteria  
• 
Patients post myocardial infarction (ST wave elevated MI or Non-ST wave 
elevated MI) within the past three months (confirmed by elevated blood 
biomarkers or electrocardiographic changes), in which the procedure/ recovery 
uncomplicated and are therefore classified as low risk. 
• 
Aged 40 years or above. 
• 
Any ethnicity. 
• 
Individuals with diet controlled type 2 diabetes mellitus  

 
19 
7.1.2 Exclusion criteria  
• 
Previous MI 
• 
Under 40 years of age. 
• 
Unable to provide valid informed consent (lack of mental capacity). 
• 
Not had a cardiac event diagnosed within the past three months. 
• 
Existing comorbidities including cancer, chronic kidney disease and gastro-
oesophageal diseases. 
• 
Unstable coronary disease. 
• 
Diagnosed diabetes and use of medication. 
• 
Disease or conditions with a prognosis of less than 6 months to end of life 
(palliative care). Any known blood borne disease. 
• 
Unable to stand and engage in light-intensity stepping. 
 
7.2  
Sampling 
7.2.1  Size of sample 
An estimated sample size was calculated using G* Power (version 3.1.9.4). Based on previous 
data (Bailey, et al., 2019), it was estimated that 18 participants would be needed to detect a 
medium effect size (f=0.5) difference in iAUC postprandial glucose between conditions with 
95% power at an alpha level of 5% and within-person correlation of 0.5. To allow for 20% drop 
out, 23 participants will be recruited. If drop out occurs  and recruitment is lower than 18 , 
participants will be replaced to ensure minimum recruitment is met. This decision will be 
pragmatic in accordance with study timeline.  
 
7.2.2  Sampling technique 
Eligible patients will be approached during their phase 2 CR consultation with the CR 
multidisciplinary team. Convenience sampling will be used to ensure sufficient recruitment to the 
study.  
 
7.3 
 Recruitment 
7.3.1 Sample identification 

 
20 
Participants will be identified by a member of the university research team who will regularly 
attend CR initial assessment clinics. This member is also employed at Bedford Hospital as a 
Cardiac Rehabilitation Exercise Specialist. They will have access to the clinic list and medical 
notes prior to the consultation, where they can be screened to check who may be eligible for 
the study. This is usual practice as part of the role of a Cardiac Rehabilitation Exercise 
Specialist. All members of the research team involved in recruitment will have an NIHR 
research passport and will have completed secondary GCP (Cardiac Rehabilitation Exercise 
Specialist). Eligible patients will be approached by the Cardiac Rehabilitation Exercise 
Specialist to ask if they would be interested in volunteering to take part in the study.  
Participants will be approached after their initial CR appointment by a member of the research 
team to invite them to take part in the study. An introduction to the study will be given and the 
patient will be given a participant information sheet (PIS) to take away. A consent to contact 
form will be completed that allows the research team to call the patient to discuss the study 
further and explore whether they are interested in participating. It is optional and refusal to do 
so does not in any way affect their usual standard of care. If they complete a consent to contact 
form, the patient will be given at least 24 hours to read the PIS and discuss with friends and 
family, to carefully consider their participation in the study.  
 
7.3.2 Consent 
Only patients with capacity to consent will be considered eligible for the study. If the patient 
would then like to participate in the study, an informed consent form will be given for them to 
complete and sign. Should a patient lose capacity during the follow up period, they will be 
withdrawn from the study. Identifiable data or blood samples already collected with consent 
would be retained and potentially used in the study. No further data or samples would be 
collected or any other research procedures carried out. 
For an individual to have capacity to consent they will: understand the purpose and nature of 
the research; understand what the research involves, its benefits (or lack of benefits), risks 
and burdens; understand the alternatives to taking part; be able to retain the information long 
enough to make an effective decision; be able to make a free choice; be capable of making 
this particular decision at the time it needs to be made (though their capacity may fluctuate, 
and they may be capable of making some decisions but not others depending on their 
complexity). 
 

 
21 
8 
ETHICAL AND REGULATORY CONSIDERATIONS 
8.1 
Assessment and management of risk 
Physical Activity 
As patients will be asked to do light intensity physical activity, there is a very small risk of injury 
and falls. However, risks will be kept very minimal by asking the patient to complete a health 
questionnaire to check for any contraindications. If any symptoms become evident during the 
study, participants will be asked to stop straight away and monitored for an appropriate amount 
of time. There will also always be a first aider available on site. 
Blood Collection 
There is a small risk of bruising associated with blood collection. To reduce this, research 
members will be trained in the appropriate blood collection technique, which adhere to 
published guidelines.  
There is a very small risk of contamination from blood sample collection. However, these risks 
will be minimized by using protective equipment, disinfecting all re-useable equipment and 
screening all participants with a health questionnaire before they take part in the study. 
Individuals will be asked not to take part in the study if they have a blood borne disease or 
virus.  
 
Further heart abnormality findings 
An ECG will be carried out by a suitably trained professional prior to each condition taking 
place. If any changes to the electrical activity of the heart are observed, the study will not be 
carried out and the participant will be advised to get in contact with their GP or an ambulance 
will be called, depending on what the findings are. 
 
Echocardiogram scanning 
There is a small risk of a skin reaction to the gel used during scan. However, it is a hypo-
allergenic gel. To minimise this risk further, a small patch test will be carried out prior to the 
study taking place. If there is any redness around the area applied, the scan will not go ahead.  
Further to this, there may be slight discomfort to the participant when the scan is taking place, 
through either a cold gel, slight pressing on the chest or being unclothed on their top half.  It 
will be highlighted to them that it is important to inform the researcher of any discomfort and 
that they are free to stop the study at any time. If any areas of concern are highlighted during 
the echocardiogram, the participant’s GP will be informed by writing a letter to them.  

 
22 
 
If an adverse event occurs, there is a qualified advanced first aider (also trained in AED and 
gas) on site in the laboratory at all times. There is access to first aid equipment (first aid box, 
AED, oxygen) and a telephone, where an ambulance would be called. The GP will be notified 
of any event that occurs during data collection. Likewise, if there are any incidental findings 
regarding the results obtained during the study, the GP will be notified via a letter detailing the 
findings.  
 
8.2  
 Research Ethics Committee (REC) and other Regulatory review & reports 
Before the start of the study, a favourable opinion will be sought from the NHS REC. 
• 
Substantial amendments that require review by NHS REC will not be implemented until 
that review is in place and other mechanisms are in place to implement at site.   
• 
All correspondence with the REC will be retained. 
• 
It is the Chief Investigator’s responsibility to produce the annual reports as required. 
The Chief Investigator will notify the REC of the end of the study. 
• 
An annual progress report (APR) will be submitted to the REC within 30 days of the 
anniversary date on which the favourable opinion was given, and annually until the 
study is declared ended. 
• 
If the study is ended prematurely, the Chief Investigator will notify the REC, including 
the reasons for the premature termination. 
• 
Within one year after the end of the study, the Chief Investigator will submit a final 
report with the results, including any publications/abstracts, to the REC. 
 
Regulatory Review & Compliance  
Before patients are enrolled into the study, the Chief Investigator will ensure that appropriate 
approvals from participating organisations are in place. Specific arrangements on how to gain 
approval from participating organisations are in place and comply with the relevant guidance. 
For any amendment to the study, the Chief Investigator, in agreement with the sponsor will 
submit information to the appropriate body in order for them to issue approval for the 
amendment. The Chief Investigator or designee will work with sites (R&D departments at NHS 
sites as well as the study delivery team) so they can put the necessary arrangements in place 
to implement the amendment to confirm their support for the study as amended. 

 
23 
Amendments  
If the sponsor wishes to make a substantial amendment to the REC application or the supporting 
documents, the sponsor will submit a valid notice of amendment to the REC for consideration. 
The REC will provide a response regarding the amendment within 35 days of receipt of the notice. 
It is the sponsor’s responsibility to decide whether an amendment is substantial or non-
substantial for the purposes of submission to the REC. 
Amendments will also to be notified to the national coordinating function of the UK country where 
the lead NHS R&D office is based and communicated to the participating organisations (R&D 
office and local research team) departments of participating sites to assess whether the 
amendment affects the NHS permission for that site.  
In all instances the protocol will describe: 
• 
The process for making amendments.  
• 
Who will be responsible for the decision to amend the protocol and for deciding 
whether an amendment is substantial or non-substantial? 
• 
How substantive changes will be communicated to relevant stakeholders (e.g., REC, 
R&D, regulatory agencies). 
• 
How the amendment history will be tracked to identify the most recent protocol 
version. 
 
8.3  
Peer review 
As this study forms part of a PhD project, it has been reviewed by two academic supervisors.  
 
8.4  
Patient & Public Involvement 
Cardiac Rehabilitation Team at Bedford Hospital 
Regular meetings will be held between the Bedford Hospital Cardiac Rehabilitation team and 
the study investigators to discuss how to conduct the study in terms of participant recruitment, 
data collection and dissemination.  
 
Patient and Public Involvement 
A PPI focus group study session has been held with post MI patients to discuss the study 
design and coordination. This helped the research team to understand any difficulties with 

 
24 
recruitment that they may face, as well as how best to conduct the study. They have also been 
shown patient facing documents to ensure they are suitably aimed at the target population.  
 
8.5 
Protocol compliance  
Accidental protocol deviations can happen at any time. If they are to occur, they must be 
adequately documented and reported to the Chief Investigator and Sponsor immediately.  
Deviations from the protocol which are found to frequently recur are not acceptable, will require 
immediate action and could potentially be classified as a serious breach. Here, they will also 
be reported to the NHS REC.  
 
8.6 
Data protection and patient confidentiality  
All investigators and study site staff will comply with the requirements of the Data Protection 
Act 2018 with regards to the collection, storage, processing and disclosure of personal 
information and will uphold the Act’s core principles, to ensure that patient confidentiality is 
maintained at all times.  
Personal information on source documentation will be filed in a locked cabinet, with only the 
core research members allowed access. Upon registration to the study, participants will be 
given a unique participant ID number, which will henceforth be used in all data collection within 
the study. This will be determined using a number system (Move-01, etc.). A confidential log 
will be kept by the research team to identify participants with their anonymous ID numbers, 
which will be encrypted on a secure computer. All other electronic documentation will also be 
encrypted. Only direct members of the research team will have access to the data, and will be 
listed on the study’s delegation log.  Where data is transmitted to sponsors, if necessary, it will 
only be identifiable by its participant ID number, thus not becoming patient identifiable at any 
time.  
Upon completion of the study, data will be stored for a minimum of 5 years. The data custodian 
for the Project is Dr Joanna Richards, Lecturer for Clinical Physiology.  
 
8.7 
Indemnity 
The University of Bedfordshire holds insurance and will provide indemnity to cover relative 
liabilities associated to this research project. Please see the University of Bedfordshire 
'Certificate of Employers Liability Insurance' and 'Professional Indemnity Certificate', which 
includes insurance cover for research. 
 

 
25 
8.8 
Access to the final study dataset 
All members of the research team will have access to the final study dataset. Following 
publication of the study, access may be available for secondary analysis of the anonymized 
dataset on reasonable request to the Chief Investigator, which would not be patient 
identifiable. All patient documentation will reflect the future use of these data in research if 
necessary.  
 
9 
DISSEMINIATION POLICY 
9.1  
Dissemination policy 
All data arising from the study will be property of the University of Bedfordshire. On completion 
of the study, the data will be analysed and a final study report prepared. The full study report 
will be accessible by all, as it will be made publically available. The chief investigator will have 
the right to publish the final report. Participants will be notified of the outcome of this study by 
receiving a summary of its findings. Overall, a manuscript will be written for submission to a 
peer reviewed journal.  
 
9.2  
Authorship eligibility guidelines and any intended use of professional writers 
Authorship will be based on the following 4 criteria, in accordance with the ICMJE: 
• 
Substantial contributions to the conception or design of the work; or the acquisition, analysis, 
or interpretation of data for the work; AND 
• 
Drafting the work or revising it critically for important intellectual content; AND 
• 
Final approval of the version to be published; AND 
• 
Agreement to be accountable for all aspects of the work in ensuring that questions related 
to the accuracy or integrity of any part of the work are appropriately investigated and 
resolved. 
• 
(Anderson et al., 2016, Azevedo et al., 2016, Bailey and Locke, 2015, Bailey et al., 
2019, Benatti and Ried-Larsen, 2015, Dempsey et al., 2016, Dimina and Mariotti, 
2019, Healy et al., 2011, Henson et al., 2016, Ibanez et al., 2018, Kerr et al., 2009, 
Lesman-Leegte et al., 2009, Mikines et al., 1988, Ning et al., 2010, Oikonomou et al., 
2019, Patel et al., 2009, Thygesen et al., 2007, Tremblay et al., 2017, Watson et al., 
1988) 
 

 
26 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10 REFERENCES 
ANDERSON, L., OLDRIDGE, N., THOMPSON, D. R., ZWISLER, A. D., REES, K., 
MARTIN, N. & TAYLOR, R. S. 2016. Exercise-Based Cardiac Rehabilitation for 
Coronary Heart Disease: Cochrane Systematic Review and Meta-Analysis. J Am Coll 
Cardiol, 67, 1-12. 
 
AZEVEDO, P. S., POLEGATO, B. F., MINICUCCI, M. F., PAIVA, S. A. & ZORNOFF, L. 
A. 2016. Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological 
Mechanisms and Pharmacologic Treatment. Arq Bras Cardiol, 106, 62-9. 
 
BAILEY, D. P. & LOCKE, C. D. 2015. Breaking up prolonged sitting with light-intensity 
walking improves postprandial glycemia, but breaking up sitting with standing does 
not. J Sci Med Sport, 18, 294-8. 
 
BAILEY, D. P., ORTON, C. J., MAYLOR, B. D. & ZAKRZEWSKI-FRUER, J. K. 2019. 
Cardiometabolic Response to a Single High-intensity Interval Exercise Session Versus 
Breaking up Sedentary Time with Fragmented High-intensity Interval Exercise. 
International journal of sports medicine, 40, 165-170. 
 
BENATTI, F. B. & RIED-LARSEN, M. 2015. The Effects of Breaking up Prolonged Sitting 
Time: A Review of Experimental Studies. Med Sci Sports Exerc, 47, 2053-61. 

 
27 
 
DEMPSEY, P. C., LARSEN, R. N., SETHI, P., SACRE, J. W., STRAZNICKY, N. E., 
COHEN, N. D., CERIN, E., LAMBERT, G. W., OWEN, N., KINGWELL, B. A. & 
DUNSTAN, D. W. 2016. Benefits for Type 2 Diabetes of Interrupting Prolonged 
Sitting With Brief Bouts of Light Walking or Simple Resistance Activities. Diabetes 
care, 39, 964-972. 
 
DIMINA, L. & MARIOTTI, F. 2019. The Postprandial Appearance of Features of 
Cardiometabolic Risk: Acute Induction and Prevention by Nutrients and Other Dietary 
Substances. Nutrients, 11. 
 
HEALY, G. N., MATTHEWS, C. E., DUNSTAN, D. W., WINKLER, E. A. & OWEN, N. 
2011. Sedentary time and cardio-metabolic biomarkers in US adults: NHANES 2003-
06. Eur Heart J, 32, 590-7. 
 
HENSON, J., DAVIES, M. J., BODICOAT, D. H., EDWARDSON, C. L., GILL, J. M. R., 
STENSEL, D. J., TOLFREY, K., DUNSTAN, D. W., KHUNTI, K. & YATES, T. 
2016. Breaking Up Prolonged Sitting With Standing or Walking Attenuates the 
Postprandial Metabolic Response in Postmenopausal Women: A Randomized Acute 
Study. Diabetes care, 39, 130-138. 
 
IBANEZ, B., JAMES, S., AGEWALL, S., ANTUNES, M. J., BUCCIARELLI-DUCCI, C., 
BUENO, H., CAFORIO, A. L. P., CREA, F., GOUDEVENOS, J. A., HALVORSEN, 
S., HINDRICKS, G., KASTRATI, A., LENZEN, M. J., PRESCOTT, E., ROFFI, M., 
VALGIMIGLI, M., VARENHORST, C., VRANCKX, P., WIDIMSKÝ, P. & GROUP, 
E. S. C. S. D. 2018. 2017 ESC Guidelines for the management of acute myocardial 
infarction in patients presenting with ST-segment elevation: The Task Force for the 
management of acute myocardial infarction in patients presenting with ST-segment 
elevation of the European Society of Cardiology (ESC). European heart journal, 39, 
119-177. 
 
KERR, A. J., BROAD, J., WELLS, S., RIDDELL, T. & JACKSON, R. 2009. Should the first 
priority in cardiovascular risk management be those with prior cardiovascular disease? 
Heart, 95, 125-9. 
 
LESMAN-LEEGTE, I., JAARSMA, T., COYNE, J. C., HILLEGE, H. L., VAN 
VELDHUISEN, D. J. & SANDERMAN, R. 2009. Quality of life and depressive 
symptoms in the elderly: a comparison between patients with heart failure and age- and 
gender-matched community controls. J Card Fail, 15, 17-23. 
 
MIKINES, K. J., SONNE, B., FARRELL, P. A., TRONIER, B. & GALBO, H. 1988. Effect 
of physical exercise on sensitivity and responsiveness to insulin in humans. Am J 
Physiol, 254, E248-59. 
 
NING, F., TUOMILEHTO, J., PYORALA, K., ONAT, A., SODERBERG, S. & QIAO, Q. 
2010. Cardiovascular disease mortality in Europeans in relation to fasting and 2-h 
plasma glucose levels within a normoglycemic range. Diabetes Care, 33, 2211-6. 
 
OIKONOMOU, E., SIASOS, G., TSIGKOU, V., BLETSA, E., PANOILIA, M. E., 
OIKONOMOU, I. N., SINANIDIS, I., SPINOU, M., PAPASTAVROU, A., 

 
28 
KOKOSIAS, G., ZAROMITIDOU, M., STAMPOULOGLOU, P., SPARTALIS, M., 
VAVURANAKIS, M., STEFANADIS, C., PAPAVASSILIOU, A. G. & 
TOUSOULIS, D. 2019. Coronary artery disease and endothelial dysfunction: Novel 
diagnostic and therapeutic approaches. Curr Med Chem. 
 
PATEL, D. A., SRINIVASAN, S. R., CHEN, W. & BERENSON, G. S. 2009. Influence of the 
metabolic syndrome versus the sum of its individual components on left ventricular 
geometry in young adults (from the Bogalusa Heart Study). Am J Cardiol, 104, 69-73. 
 
THYGESEN, K., ALPERT, J. S., WHITE, H. D. & JOINT, E. S. C. A. A. H. A. W. H. F. T. 
F. F. T. R. O. M. I. 2007. Universal definition of myocardial infarction. Journal of the 
American College of Cardiology, 50, 2173-2195. 
 
TREMBLAY, M. S., AUBERT, S., BARNES, J. D., SAUNDERS, T. J., CARSON, V., 
LATIMER-CHEUNG, A. E., CHASTIN, S. F. M., ALTENBURG, T. M. & 
CHINAPAW, M. J. M. 2017. Sedentary Behavior Research Network (SBRN) - 
Terminology Consensus Project process and outcome. Int J Behav Nutr Phys Act, 14, 
75. 
 
WATSON, D., CLARK, L. A. & TELLEGEN, A. 1988. Development and validation of brief 
measures of positive and negative affect: the PANAS scales. Journal of personality and 
social psychology, 54, 1063-1070.