A Strength-building Lifestyle-integrated Intervention for Tackling Double Burden of Sarcopenic Patients With Coronary Artery Disease: A Pilot Randomized Controlled Trial
Phase: NA
Conditions: Sarcopenia, Coronary Artery Disease
Sponsor: The University of Hong Kong

Study protocol (Version no.01, dated 2022.05.30) 
 
 
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Study Title: A strength-building lifestyle-integrated intervention for tackling double 
burden of sarcopenic patients with coronary artery disease: A pilot randomized controlled 
trial  
Background  
The world’s older population continues to grow rapidly. More people survive into later 
life and living with multiple chronic diseases, including cardiovascular disease. 
Cardiovascular disease is highly prevalent among the older population, as more than 70% 
of the patients who develop cardiovascular disease by 70 years of age.1 In particular the 
coronary artery disease (CAD), as a function of normal physiological age-related 
degeneration in the coronary arteries. CAD is characterized by atherosclerotic plaque 
accumulation in the coronary arteries, causing insufficient myocardial perfusion. CAD is a 
major burden of non-communicable disease that has reached an unequivocal pandemic 
status globally and regionally.2 It is common for this vulnerable cohort to have multi-
morbidity,1 particularly those age-related conditions, such as sarcopenia. 
Sarcopenia, a progressive and generalized skeletal muscle disorder characterized by 
accelerated loss of muscle mass and function, which is related to functional and 
physiological impairments.3 It has emerged as a public health priority which affects 10% 
of the general older population.4 Individuals with sarcopenia are associated with profound 
adverse health outcomes, including increased incidents of falls and fractures, functional 
decline and increased all-cause mortality.5 The prevalence of sarcopenia increases to 31.4% 
among the individuals with cardiovascular disease, such prevalence rate is the highest when 
compared to people suffering from other comorbidities, including dementia, diabetes and 
respiratory disease.6 Accumulating empirical evidence exists to indicate sarcopenia as an 
important prognostic factor in patients with CAD. A recent meta-analysis (N = 10) found 
that CAD patients with sarcopenia had more than a double of higher rate of major adverse 
cardiovascular outcomes (hazard ratio = 2.27, 95% confidence interval: 1.58 – 3.27) than 
the non-sarcopenic counterpart.7 The biological mechanisms underpinning sarcopenia and 
atherosclerosis are yet to be fully elucidated, several shared pathophysiological and 
behavioral pathways appear to underlie the progression of both conditions, including 
endothelial dysfunction, arterial stiffness, inflammation and physical inactivity.8 In 
particular, empirical studies reported more consistent association of lower limb muscle 
function with atherosclerosis in CAD patients, rather than the muscle function of upper 
limb.9 The potential explanation may be related to the decline in lower limb muscle 
function results in reduced physical activity, which then lead to progression of both 
sarcopenia and atherosclerosis in patients with CAD. Furthermore, skeletal muscle acts as 
an endocrine organ which secretes myokines during muscle contractions. This bioactive 
substance protects coronary arteries against progression of atherosclerosis and stabilization 
of atherosclerotic plaques through anti-inflammatory effects.10 Reduced myokines level 
jeopardizes such cardio-protective effects in sarcopenic CAD patients. Altogether, the 
vicious cycle between reduced muscle mass/strength and atherosclerosis underscores the 
urgency of managing sarcopenia in the population with CAD.   
Currently, no drugs have proved to be effective and safe for treating sarcopenia.3 Instead, 
clinical practice guidelines recommend exercise as the primary treatment for 
sarcopenia.11,12 The evidence of resistance exercise in improving skeletal muscle mass and 

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strength in older adults with sarcopenia is especially compelling.13 Nutritional support in 
terms of essential amino acids and high-protein supplements have also been used to manage 
sarcopenia in older adults. However, the clinical benefits of nutritional interventions 
without exercise are less clear. A recent network meta-analysis (N = 26)14 examined the 
comparative effects of exercise, nutrition and combined exercise and nutrition 
interventions on health outcomes in older adults with sarcopenia. The findings indicated 
that both exercise alone and the combination of exercise and nutrition have beneficial 
effects on muscle strength and physical performance, but not nutritional interventions 
alone.14 Physical inactivity is not only a major contributor to sarcopenia and negative health 
outcomes in older adults,15 but also a significant predictor for the development and 
progression of CAD.16 Aerobic exercise has been the focus for primary and secondary 
prevention for CAD. Indeed, resistance exercise, particularly low-to-moderate intensity 
[30-69% of 1-Repetition Maximum (1 R-M)], demonstrates similar or even greater 
beneficial effects on blood pressure and lipid profiles as compared to aerobic and high-
intensity resistance training.17  
 
Despite these encouraging findings on the beneficial effects of resistance-based 
exercise on sarcopenia and CAD separately, no study has been done to examine its effects 
on patients having the co-existence of sarcopenia and CAD, leaving a significant gap in 
the literature. Indeed, enabling this vulnerable cohort to adopt and maintain regular 
resistance exercise remains a great challenge. Older adults have reported perceived 
difficulty, time constraints and boredom as obstacles to resistance exercise.18 An effective 
yet sustainable intervention needs to address these challenges/obstacles. Previous studies 
have highlighted the importance of enhancing older people’s self-efficacy in performing 
exercise in order to improve exercise adoption and adherence.19,20 Moreover,  opportunities 
to resistance training, indeed, emerge around the clock in the routine of an individual. 
Assisting older adults to integrate exercise into daily activities can maximize the training 
benefits and overcome barriers to exercise, and thus improve exercise adoption and 
adherence.21 Therefore, this study aims to develop a strength-building lifestyle-integrated 
intervention for sarcopenic CAD patients and to examine the feasibility and preliminary 
effects of this intervention on skeletal muscle mass, muscle strength, physical performance, 
cardiac-related functional status and health-related quality of life (HRQoL), psychological 
distress, major adverse cardiovascular and cerebral events (MACCE) and hospital 
readmission rates. Physical performance will be the primary outcome, while the remaining 
will be the secondary outcomes. 
Research plan and methodology  
Study design 
This study will include an assessor-blinded two-arm prospective pilot randomized 
controlled trial (RCT) and a qualitative study to determine the feasibility, acceptance and 
engagement experience of the participants in the strength-building lifestyle-integrated 
intervention with assessments measured at baseline, 3 months and 6 months after 
randomization.  
Study setting and participants 

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This study will recruit subjects in Care for Your Heart, a cardiac patient mutual support 
organization. Patients fulfilling the following eligibility criteria will be invited to join the 
study: 1) Chinese adults with a confirmed diagnosis of CAD; 2) age ≥60 years or older; 3) 
presence of sarcopenia according to the diagnostic criteria defined by the Asian Working 
Group for Sarcopenia22: low skeletal muscle mass (measuring the appendicular skeletal 
muscle mass with bioelectrical impedance analysis: <7.0 kg/m2 for men and <5.7 kg/m2 
for women), accompanied by low muscle strength (handgrip strength <28 kg for men and 
<18 kg for women); 4) free from ischemic symptoms when performing activities of daily 
living; 5) living in the community. Patients who cannot read Chinese or with impaired 
cognition (Abbreviated Mental Test score ≤6) or communication, a pacemaker or 
implantable cardioverter defibrillator precluding the use of bioelectrical impedance 
analysis for body composition assessment, physical limitations precluding exercise training, 
with any contraindication for exercise, any terminal or unstable conditions (e.g., malignant 
arrhythmia, severe aortic stenosis, cancer), admitted or recently completed a structured 
cardiac rehabilitation program within the past 6 months will be excluded.  
The sample size for this pilot study was estimated based on the primary outcome (i.e., 
functional capacity) to be measured by the Short Physical Performance Battery (SPPB). 
The literature indicated the minimal clinically importance difference is >1 point of SPPB23 
and the SD estimate is 4.2 in the population with cardiovascular disease, giving rise to the 
standardized effect size as 0.28. According to the method proposed by Whitehead et al.,24 
a sample size of 20 per study arm for the pilot study would give the future main trial 80% 
power at 5% level of significance to detect the between-group changes in the primary 
outcome at post-intervention time points. The total sample size is therefore 40. They will 
be randomly allocated in a 1:1 ratio, to receive the strength-building intervention or usual 
care. All participants in the intervention group will be invited to take part in a face-to-face 
qualitative interview to explore the feasibility and acceptability of the intervention. The 
interviews will be conducted individually in the center of the Care For Your Heart. Each 
interview will be audio-recorded and will last for approximately 60 minutes. 
 
Control group: Usual care  
The control group will receive routine care that they currently receiving provided by their 
primary healthcare providers, which include unstructured patient education on lifestyle 
modification. The usual care does not include structured exercise training. 
 
Intervention group: A strength-building lifestyle-integrated intervention  
Additional to the usual care provided by the primary healthcare providers, the intervention 
group will participate in a 12-week strength-building intervention to be delivered by an 
exercise specialist, who is required to have a Bachelor’s degree in physical education, 
sports science, physiotherapy or equivalent, and at least 2 years of post-graduate experience. 
He/she will receive two weeks of training on sarcopenia and CAD, risk assessment and the 
exercise protocol. A blended mode of supervised and unsupervised community-based and 
online sessions, and telephone support will be used to optimize the training effects (Table 
1). The training platform will be gradually shifted from in-person to online coaching, and 
then unsupervised self-practice with telephone support. The training schedule for 

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supervised sessions will last for 60 minutes per session, two sessions per week. Featuring 
with a lifestyle-integrated component of the intervention, the participants will be 
encouraged to self-practice the taught exercise skills on a daily basis by integrating into 
their daily routine.   
     The implementation is guided by an individualized, progressive, low-to-moderate 
intensity resistance-based exercise protocol, which has been designed according to the 
guidelines published by the American College of Sports Medicine,25 guidelines for exercise 
prescription to reverse frailty26,27 and the European College of Cardiology guidelines on 
exercise for patients with cardiovascular diseases.28 Prior to the exercise training, the 10-
Repetition Maximum (10-RM) test will be performed for estimating the 1-Repetition 
Maximum will be performed to guide the exercise prescription. A 3-phase approach, 
starting from familiarization, consolidation to habituation, will be adopted to enable 
participants to gradually incorporate resistance exercise into their day-to-day habit.      
     In the first two weeks of the familiarization phase, a community-based training will be 
adopted to let participants be familiar with the exercise protocol and to master the skills of 
the different types of resistance movements that can be done in everyday activities. The 
training schedule is 2 sessions per week and will take place in the community centers close 
to the participants’ residential area in a small group format (4 participants/group). This 
training component will start with warm-up, followed by core exercise training, and cool-
down exercise. A series of flexibility training and stretching will be performed during the 
warm-up and cool-down phases (15 minutes in total). The core exercise session will 
comprise balance and resistance (40 minutes) training, with 5 minutes break in between. 
The exercise protocol will include strength-building training with simple elastic equipment, 
such as elastic bands, cuff weights, and Gymstick™. Gymstick™ consists of a lightweight 
shaft and elastic tubing with foot straps connected to each end of the shaft. It is inexpensive, 
safe and can provide resistance training to all major muscle groups. Different resistance 
levels are available and the load on each Gymstick™ can be titrated by rolling the bar to 
shorten the elastic tubing. The resistance load will be individualized according to the 
periodically estimated 1-RM on a two-weekly interval. The resistance training will focus 
on large muscle groups over different body parts and will start with higher repetitions (e.g., 
15 repetitions) at a lower intensity (30% of 1-RM) to build muscle endurance, confidence, 
and for mastering appropriate movement skills. This will progress to fewer repetitions (e.g., 
7 – 8 repetitions) at greater intensity (i.e., 60 – 69% of 1-RM) to build muscle power. The 
progression will base on the OMNI scale, a validated 11-point perceived exertion scale for 
assessing the perceptions of exertion when performing resistance exercise.30 The numbers 
on the scale represent a range of exertion levels from 0 (extremely easy) to 10 (extremely 
difficult). Patients’ symptom status will also be monitored and the exercise intensity will 
be titrated to ensure patients are free from ischemic symptoms. Other exercise that can be 
integrated into everyday activities without special exercise equipment will also be included: 
single limb stance with and without arm, walking heel to toe, rock the boat, back leg raises, 
side leg raises, balancing wand, wall pushups, marching in place, toe lifts and calf stretches. 
Other than prescribing the number of repetitions and sets for these different forms of 
exercise, the participants will be equipped with the knowledge and skills about the 
strategies/principles to improve balance and strength in everyday activities. For instance, 
they are suggested to perform a tandem stance while watching television, and then 
upgraded to standing on one leg.  

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     From Week 3 and 4, the exercise specialist will deliver supervised home-based training, 
with one in-person session via home visits and one session to be delivered remotely via an 
online platform (Zoom). Apart from ensuring the same training principles for the intensity 
as those in the community-based group training sessions, the exercise specialist will 
observe the home environment, explore the daily routine of patients and provide 
individualized advice on the integration of the exercise tasks into their daily activities. Then 
the supervision will gradually tail off from Week 5 and onwards, from online supervised 
sessions, to unsupervised self-practice sessions. To ensure proper progression of the 
training intensity, an in-person supervised home visit as a booster session will be given at 
Week 9, the beginning of the habituation phase. The remaining sessions in this phase will 
all be unsupervised self-practice sessions. Telephone follow-ups will be arranged at Week 
10 – 12 by the exercise specialist, to offer continuous support and guidance to the 
participants. He/she will help participants to resolve any difficulties and barriers that they 
may encountered when integrating the exercise into their daily life. An exercise logbook 
will be used to document the exercise pattern of each participant.   
Table 1. Schedule of the strength-building lifestyle-integrated intervention.  
 
Fidelity monitoring and optimization  
Various methods will be used to monitor and optimize the fidelity of the study intervention. 
Assessments and record forms will be use to document the exercise prescription and 
progression. Participants’ attendance, exercise dose, performance and training response 
will be documented. A standardized manual will be developed to guide the delivery of each 
education session. The manual will also delineate the principles of exercise prescription 
and progression. Moreover, the 30% of the intervention sessions will be randomly selected 
Phase 
Week 
Session 1 
Session 2 
Familiarization 
phase 
1 
In-person community-based 
exercise 
In-person community-based 
exercise 
2 
In-person community-based 
exercise 
In-person community-based 
exercise 
3 
In-person supervised home-
based exercise 
Remote supervised home-
based exercise 
4 
In-person supervised home-
based exercise 
Remote supervised home-
based exercise 
Consolidation 
phase 
5 
Remote supervised home-
based exercise 
Unsupervised home-based 
self-practice  
6 
Remote supervised home-
based exercise 
Unsupervised home-based 
self-practice 
7 
Unsupervised home-based self-practice 
8 
Unsupervised home-based self-practice 
Habituation 
phase 
9 
In-person supervised home-
based exercise 
Unsupervised home-based 
self-practice 
10 
Unsupervised home-based self-practice + Tel support  
11 
Unsupervised home-based self-practice + Tel support 
12 
Unsupervised home-based self-practice + Tel support 

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for fidelity monitoring by the principal investigator. Face-to-face sessions, in-person and 
remotely supervised sessions will be videotaped with participants’ consent. Two post-
doctoral fellows, who will be independent of the team will review the recorded videos and 
complete a performance checklist. The collected data will be used to evaluate the feasibility 
of the intervention.  
     
Outcome evaluation 
The following measuring tools/methods will be used for outcome evaluation at baseline 
(T0), immediate post-intervention (T1), and 3 months post-intervention (T2). Physical 
performance will be the primary outcome, while the rest will be the secondary outcomes. 
Physical performance: The  Short Physical Performance Battery31 will be used to assess 
physical performance and is well validated and widely adopted in clinical and research 
settings. It is a brief performance-based assessment consisting of 3 timed-tasks, including 
standing balance, walking speed, and chair stand tests. The timed results will be rescaled 
to obtain a score ranging from 0 to 12, higher scores indicate better physical performance. 
Muscle mass and strength: The appendicular skeletal muscle mass (ASM) will be measured 
with the bioelectrical impedance analysis (In-Body). This is one of the gold-standard 
evaluation tools suggested by international guidelines for assessment of muscle mass. It is 
widely used in research and hospital setting for clients with sarcopenia. The muscle 
strength will be measured with a hydraulic dynamometer (Jamar). The standard protocol 
suggested by international guidelines will be followed, the maximum reading of at least 2 
trials using the dominant hand in a maximum-effort isometric contraction will be recorded.  
Cardiac-specific functional status: The Seattle Angina Questionnaire will be used to 
measure cardiac-related functional status. It has 19 items in 5 subscales: physical limitation, 
angina stability, angina frequency, treatment satisfaction and disease perception.32 It is 
scored on a 1–5 or 6 sequentially coded scale and subscale scores are transformed to a scale 
of 0–100, with higher scores indicating higher levels of functioning and fewer limitations. 
The Chinese version has been shown to be reliable, valid, and sensitive to clinical change.32  
Cardiac-specific HRQoL: The MacNew will be used to measure cardiac-specific 
HRQoL.33 It has 27 items scored on a 1-7 scale, and then global score is calculated by 
summing the item scores, with higher scores representing better HRQoL. MacNew has 
good internal consistency, test-retest reliability, concurrent and discriminant validity.33  
Psychological distress: The Patient Health Questionnaire-4 (PHQ-4)34 will be used to 
measure psychological distress. It consists of 4 items assessing anxiety and depression, to 
be responded on a 4-point Likert scale. The composite total score ranges from 0 to 12, 
higher scores indicate greater level of anxiety and depression. It has good psychometric 
properties.34 
MACCE and hospital readmission rates: will be monitored from enrollment to the study to 
3 months after the intervention through record review.  
Data collection procedure and randomization 
Ethical approval will be obtained from the institutional review board. Active recruitment 
strategies will be used by posting recruitment notes on the newsletters and Facebook of the 

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Care For Your Heart, and posters in the center. A research assistant will screen the 
eligibility of the potential participants at the center of Care for Your Heart by measuring 
the calf circumference to identify patients with possible sarcopenia. A non-elastic 
measuring tape will be used to measure both calves, those individuals with the maximum 
value meeting the guideline-specified cut-offs (<34 cm in male; <33 cm in female) will be 
invited to undergo a more in-depth evaluation according to the eligibility criteria of this 
study. All eligible patients will be invited to participate. After obtaining the written 
informed consent, the research assistant will collect the baseline data (T0), then he/she will 
randomly assign participants into the intervention or control group with block 
randomization to ensure even distribution of participants in the two study groups over the 
study period. Patients will be allocated chronologically in a 1:1 ratio by using a computer-
generated random sequence to determine the block size (4, 6 and 8) and respective study 
group allocation. The group allocation will be determined according to the random 
sequence codes placed in sealed opaque envelopes. Participants in the intervention group 
will receive the strength-building intervention whereas the control group will receive usual 
care. To minimize biases, another independent research assistant who is blinded to the 
group allocation will be responsible for collecting post-intervention data at another two 
time points (T1 and T2) in the center of the Care For Your Heart. Each assessment will last 
for approximately 30 minutes. 
Data analysis 
Statistical analysis of the outcome comparisons will be performed on the basis of the 
intention-to-treat principle. Descriptive statistics will be used to describe the characteristics 
of the sample, the feasibility of, acceptance, and compliance with the intervention. The 
baseline characteristics will be compared between the study groups using a t-test, chi-
square test or Fisher’s exact test where appropriate. Repeated measure ANOVA will be 
used to determine the effects of the intervention by comparing differential between group 
changes across the 3 time-points. All statistical analyses will performed using IBM SPSS 
27.0. All statistical tests will be two-sided, and a p-value of less than 0.05 will be 
considered statistical significant. Content analysis will be used to analyze the qualitative 
data. These data will be used to optimize the intervention design and feasibility for the full 
scale randomized controlled trial.  
 
 

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