Tilburg Health Outcomes Registry of Emotional Stress in Coronary Intervention
Conditions: Coronary Heart Disease
Sponsor: Tilburg University

NL46259.028.13 / THORESCI 
 
Tilburg health outcomes registry 
 
 
 
 
 
 
 
 
 
 
 
 
RESEARCH PROTOCOL 
 
Tilburg Health Outcomes Registry of Emotional Stress in 
Coronary Intervention (THORESCI) 
 
Current Version: 25-8-2020 
 
 

NL46259.028.13 / THORESCI 
 
Tilburg health outcomes registry 
 
 
 
PROTOCOL TITLE: Tilburg Health Outcomes Registry of Emotional Stress in Coronary Intervention 
(THORESCI) 
 
Protocol ID 
NL46259.028.13 
Short title 
THORESCI 
 
EudraCT number  
N/A 
Version 
4  
Date 
1. 29.10.2013 
2. Date amendment Refusal – 14.2.2014 
3. Date amendment Blood collection – 12.3.2015 
4. Date amendment Screener – 2.3.2018 
5. Date amendment Gender - 25.8.2020 
Coordinating 
investigator/project 
leader 
 
Dr. Nina Kupper 
 Department of Medical & Clinical Psychology Tilburg 
University 
PObox 90153, 5000LE Tilburg 
+31-13-466 
2956; 
(2175 
for 
secretary’s 
office) 
h.m.kupper@tilburguniversity.edu 
Principal investigator(s) (in Dutch: 
hoofdonderzoeker/ uitvoerder) 
 
 
Dr. Nina Kupper 
 Department of Medical & Clinical Psychology Tilburg 
University, Tilburg the Netherlands 
PObox 90153, 5000LE Tilburg 
+31-13-466 
2956; 
(2175 
for 
secretary’s 
office) 
h.m.kupper@tilburguniversity.edu 
 
Prof.dr. Jos Widdershoven 
Department of Cardiology, TweeSteden Hospital dr. 
Deelenlaan 5, 5042 AD Tilburg, the Netherlands 
 
 
Sponsor 
(in 
Dutch: 
verrichter/opdrachtgever) 
CoRPS - Center of Research on Psychology in Somatic 
diseases 
Department of Medical & Clinical Psychology Tilburg 
University, Tilburg, the Netherlands 
PO box 90153, 5000LE Tilburg 

NL46259.028.13 / THORESCI 
 
Tilburg health outcomes registry 
 
 
 
Subsidising party 
NWO Aspasia 
Independent expert (s) 
Dr. Ben Imholz, Department of Internal Medicine, 
TweeSteden hospital, Tilburg the Netherlands 
 
 
PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Head of Department (2013): 
Prof.dr. Johan Denollet 
 
 
28-3-2018 
[Coordinating 
Investigator/Project 
leader/Principal Investigator]: 
Dr. Nina Kupper 
Associate professor, PI 
 
 
21-8-2020 
 
 

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TABLE OF CONTENTS 
 
1. 
INTRODUCTION AND RATIONALE .......................................................................................... 8 
1.1 
Investigating long term effects and interrelations between psychological risk factors ......... 8 
1.2 
Exploring mechanisms of effect ..................................................................................... 9 
1.3 
Extending the PCI registry to include participation in cardiac rehabilitation ..................... 10 
1.4 
Scientific and societal relevance................................................................................... 11 
2. 
OBJECTIVES .................................................................................................................. 12 
2.1 
Primary Objectives ..................................................................................................... 12 
2.1.1 
Hypotheses ......................................................................................................... 12 
2.2 
Secondary Objectives .................................................................................................. 13 
3. 
STUDY DESIGN ............................................................................................................. 13 
4. 
STUDY POPULATION .................................................................................................... 13 
4.1 
Population (base) ....................................................................................................... 13 
4.2 
Inclusion criteria ......................................................................................................... 14 
4.3 
Exclusion criteria ........................................................................................................ 14 
4.4 
Sample size calculation ............................................................................................... 14 
5. 
METHODS ......................................................................................................................... 15 
5.1 
Study parameters/endpoints ....................................................................................... 15 
5.1.1 
Main study parameter/endpoint .......................................................................... 15 
5.1.2 
Other study parameters/endpoints ....................................................................... 16 
5.2 
Study procedures ....................................................................................................... 16 
5.2.1 
Outcome questionnaires ...................................................................................... 17 
5.3 
Withdrawal of individual subjects ................................................................................ 19 
5.3.1 
Specific criteria for withdrawal (if applicable)......................................................... 19 
5.4 
Replacement of individual subjects after withdrawal ..................................................... 19 
5.5 
Premature termination of the study ............................................................................. 19 
6. 
SAFETY REPORTING .................................................................................................... 19 
6.1 
Section 10 WMO event ............................................................................................... 19 
6.2 
AEs, SAEs and SUSARs ................................................................................................. 19 
6.2.1 
Adverse events (AEs) ........................................................................................... 19 
6.2.2 
Serious adverse events (SAEs) .............................................................................. 19 
7. 
STATISTICAL ANALYSIS ....................................................................................................... 20 
8. 
ETHICAL CONSIDERATIONS ................................................................................................. 20 
8.1 
Regulation statement ................................................................................................. 20 
8.2 
Recruitment and consent ............................................................................................ 20 
8.3 
Benefits and risks assessment, group relatedness .......................................................... 21 
8.4 
Compensation for injury .............................................................................................. 21 
9. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION ............................................... 21 
9.1 
Handling and storage of data and documents ............................................................... 21 
9.2 
Monitoring and Quality Assurance ............................................................................... 22 
9.3 
Amendments ............................................................................................................. 22 
9.4 
Annual progress report ............................................................................................... 22 

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9.5 
End of study report ..................................................................................................... 22 
9.6 
Public disclosure and publication policy ........................................................................ 22 
10. 
REFERENCES .................................................................................................................. 22 

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LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
ABR 
ABR form, General Assessment and Registration form, is the application form that is 
required for submission to the accredited Ethics Committee (In Dutch, ABR = Algemene 
Beoordeling en Registratie) 
AE 
Adverse Event 
CCMO 
Central Committee on Research Involving Human Subjects; in Dutch: Centrale 
Commissie Mensgebonden Onderzoek 
CV 
Curriculum Vitae 
IC 
Informed Consent 
METC  
 
PCI 
PI 
 
Medical research ethics committee (MREC); in Dutch: medisch ethische toetsing 
commissie (METC) 
Percutaneous Coronary Intervention 
Principal investigator 
(S)AE 
(Serious) Adverse Event  
Sponsor The sponsor is the party that commissions the organisation or performance of the 
research, for example a pharmaceutical 
company, academic hospital, scientific organisation or investigator. A party that 
provides funding for a study but does not commission it is not regarded as the sponsor, 
but referred to as a subsidising party. 
 
 
Wbp 
Personal Data Protection Act (in Dutch: Wet Bescherming Persoonsgevens) 
WMO 
Medical Research Involving Human Subjects Act (in Dutch: Wet Medisch-
wetenschappelijk Onderzoek met Mensen 
 
 

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SUMMARY 
 
Rationale: Percutaneous coronary interventions (PCI) have become mainstay treatment for acute 
coronary artery disease and the number of patients receiving PCI is vastly growing. Clinical trials have 
reported on the efficacy and effects on quality of life and mortality. Guidelines have been constructed 
for PCI treatment as well as cardiovascular prevention. However, relatively little long-term follow-up 
studies of large real-world clinical samples exist that have looked at the real-world effects of PCI 
treatment and adherence to current guidelines.  
Moreover, psychological risk factors are important in determining prognosis after PCI, and 
undergoing PCI may increase the risk of low mood. To date, studies have examined single psychological 
risk factors, without taking into account their relatedness. Moreover, guidelines are advocating 
psychosocial screening in early cardiovascular disease, but the screening test as proposed in the ESC 
Prevention guideline has not yet been validated or tested. Importantly, recent studies have indicated 
the need to examine  
Although the detrimental effects of psychological risk factors on cardiovascular prognosis are 
known, the mechanisms through which they exert these effects are yet unclear. It is to be expected 
that not one but multiple biological (inflammation, endothelial dysfunction) and behavioural (coping 
styles, poor self-care, consultation behaviour, decision making process) pathological processes play a 
role, and that these processes interact with each other. In PCI patients, the mechanisms linking 
psychological risk to poor prognosis are still to be investigated. Objective: (1) To examine the 
adherence to the prevention and PCI guidelines and the effects thereof on long term prognosis in PCI 
patients. (2) To examine effects of clustering psychological risk factors on several networks of 
potentially mediating mechanisms and long term outcomes in a large sample of PCI patients. (3) To 
evaluate the effectiveness of the adapted psychosocial screening instrument of the European Society 
of Cardiology Prevention guideline 2016. Amendment objective: in this additional analysis and 
secondary data collection made possible by ZonMw, we aim to investigate gender differences in 
screening scores as well as gender differences in the association between screening and psychological 
and medical outcome. Additionally, due to the extraordinary circumstances of the COVID-19 pandemic, 
we would like to ask participants about how this affected their cardiological care. Study design: 
Prospective observational cohort study.  Study population: All patients aged >18 admitted to the 
TweeSteden hospital for percutaneous coronary intervention are eligible. Main study 
parameters/endpoints: Predictors: Psychological (risk) factors (depression, anxiety, Type D 
personality, mindfulness, positive mood), Adherence; Outcome variables: PCI complications, 
hospitalizations, events. Additional variables: gender assessment Nature and extent of the burden 
and risks associated with participation, benefit and group relatedness: The risk associated with the 
current study is very low. For this mechanistic observational study, investigators will ask patients to fill 
out two extensive (20 pages) and then several smaller (12-15 pages) psychological surveys including 
among others questions on personality, positive and negative mood, mindfulness, work stress, and 
satisfaction with life. Preferably, questionnaires will be administered digitally by email link. For the 
additional data collection (gender + covid), an additional questionnaire is added that will be sent once 
to all participants in the fall of 2020. It will take 15 minutes to fill out this additional questionnaire. 
There are no direct benefits of participation, other than providing data to create knowledge to improve 
future treatment.   

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1. INTRODUCTION AND RATIONALE 
 
Cardiovascular disease (CVD) is a global disease burden and a leading cause of death and disability, 
with about 23.6 million people expected to die from CVD worldwide by 2030 1. Percutaneous coronary 
intervention (PCI) is a state-of-the-art non-surgical procedure to treat stenotic occlusions of the 
coronary arteries in patients with cardiovascular disease by inserting a balloon and stent into the 
diseased artery to treat the occlusion. Randomized controlled trials have shown the efficacy of this 
procedure for prognosis of cardiac patients 2,3, and this evidence is supplemented by effectiveness 
studies in real-world clinical samples that show differential prognoses after PCI in important 
subgroups, such as women, and patients with diabetes, poor cardiac pump function, or multivessel 
disease 4,5.  Also quality of life improves after PCI, both in younger and older cardiac patients 6.  
 
Besides traditional medical and demographic risk factors for poor prognosis of CVD, psychological 
factors also have been associated with poor prognosis in CVD 7. In PCI patients specifically, 
psychological factors, such as depression 8,9, lack of positive emotions 10, and feeling disabled a few 
months after the PCI 11, have shown to have a detrimental impact on mortality. Screening for these 
factors does not happen structurally, and if a screening is done, it usually comprises depression and 
anxiety only, while a range psychological risk factors have been identified. 47To do right to this myriad 
of psychosocial risk factors, we want to examine the effectivity of a psychosocial screening interview 
that is workable in clinical practice (i.e. short), and that covers the full range of established risk factors.  
1.1 Investigating long term effects and interrelations between psychological risk factors 
 
Longer term effects of PCI procedures with respect to efficacy and effectiveness until now have been 
examined over periods of on average about 3 to 4 years of follow-up 2, and focus primarily on 
complications, MI and early death, although some studies with longer follow-up periods exist 
comparing differences in prognosis for different stent types e.g., 12. With respect to psychological risk 
factors, the long-term (7-year) predictive value of depression on all-cause mortality has been shown 
8,10. However, psychological factors in these two studies have only been assessed at baseline (between 
0-6 months post-PCI), while it is important to look at depression profiles (which symptoms dominate) 
and persistence of depressive symptoms over time. It has been shown that somatic symptoms of 
depression predict mortality better than cognitive symptoms in stable coronary artery disease patient 
13-15. Also, both in heart disease patients16 as well as in the general population 17 these symptom profiles 
have been differentially related to inflammatory activity, a proposed mechanism in the relation 
between depression and cardiovascular prognosis. In patients with acute coronary syndrome 
associations have also been reported on somatic a cognitive depression scores at baseline, and 
inflammatory activity, i.e. hsCRP levels, at 1 and 3 months follow-up, suggesting that depression might 
affect prognosis 18,19.   
 
Besides the demonstrated relevance of discriminating between different psychological symptom 
profiles, it may also be important to discriminate between cardiac related and all-cause mortality and 
events, as previous studies have shown that only looking at all-cause mortality may delude the effect 
you are after. Surely, the mechanisms underlying cardiac mortality may not be equal to other 
pathophysiological processes leading to other causes of death.   
 
It is thus necessary to increase the level of detail in the relation between psychological risk and 
prognosis to be better able to pinpoint which patients are in need of additional care. To start finding 

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out more about the course and progression of heart disease in patients with psychological risk factors, 
large registries of heart disease patients that are in the early stages of heart disease are needed, and 
long follow up periods in such registries is warranted. To date, there is no registry that systematically 
screens for psychosocial risk factors, as well as systematically and regularly assesses psychological risk 
factors over longer time periods in patients undergoing a percutaneous coronary intervention. Such a 
registry is necessary to evaluate the role of psychosocial factors in the effectiveness of PCI. Therefore, 
the current study aims to extend the current standard of care registry of PCI patients to include a yearly 
inventory of events (revascularisation, MI) and mortality for at least 10 years. In addition, we aim to 
add a long term psychological survey study. These data will enable us to answer the following research 
questions: 
 
• 
What are the long term clinical, psychological and demographical predictors of cardiovascular 
events and mortality in patients that have received a PCI procedure? 
• 
How do psychological risk factors cluster together in increasing the risk of events/mortality? 
• 
How do psychological risk factors behave over long periods of time in an at-risk cardiovascular 
population? Can we identify symptom profiles over time that are useful in risk stratification? 
• 
What behavioural mechanisms play a role in explaining the association between the found risk 
factors and events/mortality? 
• 
What are the long term clinical, psychological and demographical predictors of quality of life 
in patients that have received a PCI procedure? 
• 
How does quality of life change over time? 
 
1.2 Exploring mechanisms of effect 
 
Allostatic load is increasingly used as a general indicator of cumulative burden of physiological 
dysregulation. Allostatic load is usually defined as a count-based index of multiple biomarkers including 
markers of neurohormonal activity, lipid and glucose metabolism, cardiovascular and immune system 
activity, and indices of visceral obesity 20. The proposed projects will focus on allostatic load as a 
hypothesized pathway through which emotional distress exerts its detrimental effects on 
cardiovascular health, but will take a different operational approach. To date, most previous 
mechanistic risk assessment studies have either published on the risk of individual markers or have not 
taken into account their interrelationships and interactions e.g., 21,22-25. Others have used summary 
scores of allostatic load that do not take into account higher-order constellations of dysregulations 
across multiple major regulatory systems 20. A recent novelty is to use structural equation modeling to 
examine the cardiovascular health risk of multiple individual biomarkers in the context of the system 
of interrelations 26.  
 
Importantly, psychological, behavioral and biomedical risk factors interact with, and may be 
influenced by, the major regulatory biological systems in the human body that adapt in response to 
stress. The current project will therefore take into account the interactions between the allostatic load 
components and the behavioral risk factors. By taking such a broad multisystem approach, this 
proposal will arrive at a more informative and complete cardiovascular risk assessment.    
 
Research questions that will be answered are: 

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• 
Which variables of the network of biological regulatory systems are most important in 
determining prognosis in PCI patients? 
• 
In what way are psychological risk factors related to the network of biological regulatory 
systems? Are there differences between psychological risk factors?  
• 
To what extent do behavioral factors moderate the relation between psychological risk factors 
and prognosis? 
 
1.3 Extending the PCI registry to include participation in cardiac rehabilitation 
 
Cardiac rehabilitation (CR) is a multifaceted intervention program that aims to improve physical, 
psychological and social functioning of cardiac patients after a cardiac event or therapeutic 
intervention, such as PCI 27. In addition to these primary objectives, CR also aims to induce lifestyle 
changes and improve medication adherence 27. It has been shown in previous studies that actively 
attending cardiac rehabilitation (CR) has beneficiary effects on survival after percutaneous coronary 
intervention. A recent study in 2395 consecutive patients showed that a reduction of risk of (HR=0.55) 
for all-cause mortality after a median follow-up of 6.3 years in those patients that had attended CR 28. 
Recent PCI guidelines recommend cardiac rehabilitation for all patients recovering from PCI 29. 
Unfortunately, only a limited part of eligible patients (between 13-40%) actually participate in CR 28,30. 
In the Netherlands, the same picture may be painted, with less than 1 out of 3 eligible patients 
participating 31. Recent insurance data from the Netherlands has even indicated that only a very small 
minority (11%) of patients with an elective PCI attends CR 32. At the TweeSteden hospital, all PCI 
patients are invited to participate in CR, but as yet, there is no record of who participates and who 
does not. Therefore, the current research proposal aims to extend the current medical outcome 
registry of PCI patients to include data on recruitment for and participation in cardiac rehabilitation. 
Also, data will be gathered on which combination of treatments are offered to the patient.  
 
Patients get more and more involved in their own treatment and treatment decisions. There seem to 
be large differences between specialisms though in the extent to which patients participate in the 
decisions of their own treatment. This is a very timely issue and here has been only one previous study 
examining the extent of shared decision making in patients recovering from an ischemic coronary 
event 46. Their results show that shard decision making did not happen as often as patients would want, 
and there were significant sex differences as well, with women being less informed and less involved. 
This is a Canadian study, so we are in need of a European study looking into this aspect of care.  
 
These data will enable us to answer the following research questions: 
 
• 
What is the participation rate and adherence to cardiac rehabilitation? 
• 
Which clinical, psychological and demographic variables are predictors of adherence to cardiac 
rehabilitation in patients that have received a PCI procedure? 
• 
Which phases in the patient recruitment for cardiac rehabilitation may need improvement? 
What is the role of physician adherence and what are predictors of non-participation? 
• 
To what extent was there a shared decision making process in the decision whether or not to 
start cardiac rehabilitation? 

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1.4 The role of sex and gender 
In clinical research and practice, it is of importance to consider diversity and heterogeneity. 
Women experience more psychosocial complaints such as anxiety and depression 33,34. A 
recent meta-analysis of data on over 220.000 women and 320.000 men has shown that 
depression and anxiety in men incur larger risks of poor prognosis in patients with ischemic 
heart disease compared to women 34. Differences in etiology and prognosis between men 
and women are, at the moment, not included in treatment.  
 
In addition, there are sex and gender differences in other psychological risk factors. For 
example, early life events are more prevalent in women, and the effects of these early life 
events on the incidence of heart disease is larger in women too 35. In the THORESCI study, 
the clustering of risk factors has already been examined 36 . Results showed that the profile 
characterized by anxious tension was more dominant in female patients, while hostility, 
anger and generalized distress were more common in male patients. We do not know 
whether gender will show us more diversity in risk profiles. More masculine identifying 
women may have a different risk profile as compared to more feminine women and for men 
similar discrepancies may exist. That is why the current additional project funded by ZonMW 
will focus on the role of sex and gender in psychosocial risk profiles and their association 
with outcomes.  
 
1.5 Scientific and societal relevance 
 
Cardiovascular disease comprises a considerable burden to society and patients due to increased 
health care costs and limitations to quality of life. About 25-50% of patients with cardiovascular disease 
have psychological problems as well, and these individuals also more often have precursors of 
cardiovascular disease (i.e. metabolic syndrome, hypertension) and have a worse prognosis and quality 
of life than patients without psychological risk factors. The current research proposal aims to increase 
the knowledge of explanatory mechanisms in this relation between psychological risk and poor 
outcome. This may open up new avenues for preventive and curative treatment tailored to the specific 
biological and behavioural underpinnings of individuals with psychological risk factors. Over time, 
these psychologically directed preventive and curative treatments may be able to reduce health care 
costs and thereby the burden to society.  
 
Part of the results of the proposed projects embedded within the proposal can be implemented in 
clinical practice on the short to midterm. After the psychosocial screening has been validated in the 
current study, psychosocial screening can be adopted quickly and at low cost and can help in earlier 
risk stratification. In addition, when the results of the current project would show that health 
behaviours are important moderators of the relation between psychological risk and cardiovascular 
disease progression, behavioural programs that focus on losing weight, quitting smoking, as well as 
exercise programs are readily available during CR, but could be tailored to for example Type D 
individuals, taking into account their fear of social engagement.  
 
 
On the longer term, uncovering biological mechanisms that are important in determining the 
cardiovascular risk of patients with psychological risk factors, could guide the development of 

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treatment strategies that target these biological mechanisms. For example, inflammation can be 
suppressed with anti-inflammatory drugs and it should then be investigated whether these anti-
inflammatory drugs may also reduce the risk of poor prognosis of cardiovascular disease in patients 
with psychological risk factors. Also, it is possible to train autonomic regulation of the heart using 
biofeedback. Increasing parasympathetic and decreasing sympathetic cardiac drive using biofeedback 
might be another treatment avenue.  
 
 
A further valorization aim of the current proposal is to inform and to educate. The first aim is to 
inform the public, especially patients with cardiac disease and people at risk for cardiovascular disease. 
As soon as the results of the projects are known, the researchers will contact the patient organization 
“De Hart & Vaatgroep”, to invite them to a symposium about the results of the research project. There 
have been previous contacts between our research institute CoRPS and this patient organization, so 
future contact will not be hampered by unfamiliarity. Also, outpatients of the cardiology clinic that 
participate in the study will receive a yearly newsletter informing them about the research project and 
the results. The overarching aim being that educating patients about the impact of psychological 
factors and health behaviours on disease progression and quality of life, and the mechanisms behind 
these effects, might improve adherence to treatment as well as consultation behaviour.  
 
The second aim is to educate medical specialists on the role of psychological factors in disease 
prognosis and the mechanisms involved. Together with the Brabant Medical School the applicant will 
organize a seminar during which the results of the study are reported to medical residents and 
specialists. The PI has experience in collaborating with the Brabant Medical School, as she initiated the 
development of a statistics course for medical residents for the School. 
 
2. OBJECTIVES 
2.1 Primary Objectives 
1. To establish a real-world standard for understanding disease progression and outcomes in 
cardiac patients who receive a percutaneous coronary intervention 
2. To examine the effectivity and usefulness of psychosocial screening in cardiac patients who 
receive a percutaneous coronary intervention 
3. To examine biological and behavioural mechanisms potentially explaining the link between 
psychosocial risk and cardiac prognosis.  
 
2.1.1 
Hypotheses 
 
1. The real-life standard will deviate from samples from clinical trials in descriptive statistics as 
well as in outcomes and outcome prediction. 
2. Psychosocial screening will serve a general signalling function to identify at-risk patients. These 
at-risk patients will be characterized by poorer adherence to treatment guidelines, increased 
report of symptoms and complications, as well as with a lower participation rate in cardiac 
rehabilitation.  
3. Patients with psychological risk factors such as depression, anxiety and Type D personality will 
be characterized by increased chronic low grade inflammation, more endothelial dysfunction 
and higher levels of myocardial damage markers. 

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2.2 Secondary Objectives 
1. To study socioeconomic and gender differences in prognosis after a PCI procedure and their 
interaction with psychosocial risk 
2. To examine long term course of psychosocial risk factors in cardiac patients after a PCI 
procedure.  
 
2.3 Amendment objectives 
1. to examine the relation of sex and gender with the various psychosocial risk profiles.  
2. To examine sex and gender differences in health behaviors, classical cardiovascular risk factors 
and medical history, that are known o differentially relate to the various psychosocial risk profiles.  
3. to examine the moderating role of sex aqnd gender on the relationship between psychosocial 
risk profiles and health outcomes.  
 
4. With respect to Covid-19, the current study would like to examine to what extent the THORESCI 
patient population has experienced a delay in care, and to what extent Covid-19 is related to a larger 
proportion of adverse events in the pandemic aftermath.   
 
 
3. STUDY DESIGN 
 
This is an observational cohort study, which recruits participants from the clinical standard of care PCI 
Registry at the TweeSteden Hospital. Yearly, approximately 800 patients receive a percutaneous 
coronary intervention at the TweeSteden hospital. Of these, about 400 undergo an elective or sub-
acute procedure, and these patients will be asked to participate in this research project until the 
Trigger study (a CoRPS PhD project) has ended their data collection in acute PCI patients (estimated to 
end in 2015 at the latest).  After that time, also acute PCI patients will be included. Please see below 
flow chart for an overview of the study design.   
 
 
 
 
 
 
 
 
 
 
 
Figure 1. Main PCI registry Study design 
 
4. STUDY POPULATION 
4.1 Population (base)  
 
Registry 
10 yr follow-up: events (revascularization, MI) and mortality 
Inventory of cardiac rehabilitation participation and dropout 
All patients 
receiving a PCI 
Questionnaire study 
(N=3000) 
Biomarker substudy 
(N=700) 
Yearly psychological questionnaires (12 occ over 10 yrs) 
Provision of blood samples pre-PCI, 4 days and 6 mo post-PCI 

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- 
Registry 
All patients (all ages, male and female) from the Cardiology clinic of the TweeSteden hospital who are 
going to be scheduled for elective or acute percutaneous coronary intervention for ≥1 coronary 
occlusions are to be included in the PCI standard of care registry. About 800 patients/year receive this 
procedure, which amounts to an average of 15 PCIs per week. The standard of care registry in the 
TweeSteden hospital is obligatory, because the TweeSteden hospital is a relatively new PCI centre. The 
registry includes both acute and elective PCI patients.  
 
- 
Questionnaire study 
The questionnaire study will first include patients with an elective or subacute PCI procedure (until end 
2015), who participate in above described registry, as in acute patients there is no time for pre-
procedure screening. After that time, we will also include acute PCI patients, and aim to include in total 
3000 participants in the questionnaire study over a period of 5-6 years, expecting a participation rate 
of 75%.  
 
4.2 Inclusion criteria 
In order to be eligible to participate in the Questionnaire study and the Biomarker substudy, a subject 
must meet all of the following criteria:  
• 
Aged ≥18 
• 
Sufficient understanding of the Dutch language to fill out questionnaires 
 
4.3 Exclusion criteria 
A potential subject who meets any of the following criteria will be excluded from participation in the 
Questionnaire study: 
• 
Life threatening comorbidity (e.g. metastasized cancer)  
 
4.4 Sample size calculation 
 
The essence of a registry is that the general aim is to include all patients in order to get the most 
complete picture of the real-world clinical situation and the real-world effects of treatments and risk 
factors. Therefore, sample size for the registry is unlimited. To be able to make conclusions on the 
effects of mortality, large samples and long term follow-up periods are needed as well. In the 
RESEARCH registry in Rotterdam, which also is a PCI registry, the 7-year all-cause mortality rate was 
15%. Only 7% of PCI patients die from cardiac causes. Analyses in PASS executed by a CoRPS statistician 
(dr. Zijlstra), using information from previous studies (RESEARCH registry Rotterdam), have pointed 
out that with an expected 7-year event rate of about 8% (cardiac death), an estimated hazard ratio of 
1.5 (dichotomous predictor), taking into account a predictor prevalence of 25%, with an accompanying 
an SD of 0.45 (depression data has been used for this power analysis), the minimal sample size needed 
for this study to be sufficiently powered is 2842 37. 

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5. METHODS 
5.1 Study parameters/endpoints 
5.1.1 Main study parameter/endpoint 
 
Questionnaire study 
Endpoints 
- Mortality (all-cause and cardiovascular) 
- Hospitalisations during the first year post-PCI 
- Major adverse cardiac events  (revascularization, MI, CABG, heart transplantation) 
- Health complaints (self-report) 
- Quality of life, satisfaction with life (self-report) 
 
Psychosocial screener 
Right after the PCI, in the clinic, and after consent, all participants will take part in a 5-minute screening 
interview which was adapted from the screening interview published by the European Society for 
Cardiology in their Cardiovascular Prevention guideline of 2016 (Piepoli et al., see appendix 1). During 
the past 6 months, I (PI) have been working together with an international group of researchers 
involved with the Cardiovascular prevention Guideline of European Society of Cardiology to make 
improvements to the original screener, which we have finalized recently. If participants indicate they 
are not up for an interview or the medical status precludes an interview, we will call the participant at 
4 weeks follow up.  
 
Questionnaires 
Demographic variables (Baseline and at 1 and 2 years follow-up) 
 
Date of birth, sex, educational level, work status, marital status, socioeconomic status, income level 
(8 items)  
 
Anthropometrics (All measurement occasions) 
Waist and hip circumference, weight, length (Baseline only), birth weight (Baseline only), gestational 
period (Baseline only) (6 items) 
 
Lifestyle variables (all measurement occasions)   
Smoking, alcohol use, diet, exercise 
 
Personality (Baseline and at 1 and 2 years follow-up) 
 
Neuroticism (EPQ-NE), extraversion (EPQ-NE), Type D (DS-14), mindfulness (FFMQ), optimism (LOT-
R), cardiac self- efficacy (CSAQ),  resilience (RS-NL), hostility (MC 7-item Williams subscale) 
Spielberger trait Anger Questionnaire (STAQ 10 items), self-rating inventory for PTSD (SRIP 22 items) 
at 1 and 6 month follow-up  
 
Mood (all measurement occasions) 
  
Depression (PHQ-9, BDI-II), general anxiety (GAD-7), positive mood (GMS12), Worry (PSWQ) 

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Emotion regulation (Baseline, 30 days, and at 1 and 2 years follow-up)  
coping style (CISS), psychological mindedness (BIPM) 
Shared decision making: 9 item SDM-Q-9 at T1 and T2  
 
Chronic stress (Baseline and at 1 and 2 years follow-up)  
 
  
Life events (Levensgebeurtenissen Vragenlijst), effort-reward imbalance (ERI), marital quality 
(MMQ-6) 
 
Additional Questionnaire 
Gender - Bem sex roles inventory (12 items) + some demographic role division questions 
(breadwinner, household work, care and relationship tasks). The Bem sex roles inventory 38 
measures feminine and masculine gender roles.  
Covid-19: 13 questions on the alterations in medical care in the past half year (delay, video calls, etc), 
whether patients were infected and /or hospitalized for Covid-19. And, if so, how did it affect their 
heart condition until now.   
5.1.2 Other study parameters/endpoints 
Clinical variables (see appendix II) 
 
5.2 Study procedures 
 
Inclusion procedure Questionnaire study: 
When after catheterisation the decision is made that the patient is a candidate for PCI, the heart team 
discusses its case, and a letter and information brochure is sent. In this mailing the patient will be 
informed about the registry as well as the questionnaire and biomarker study. After the PCI procedure, 
a research assistant will explain the questionnaire study to the patient and will give the patient 
information letter, informed consent, refusal form, first questionnaire and return envelope. They are 
asked to decide whether they are willing to participate in the study, and if so, whether they want to 
fill out the questionnaire and return it together with the signed informed consent within the next week. 
If not, they are asked to return the refusal form. If after 2 weeks nothing has been received, a phone 
call is made to the patient to ask whether the patient has decided whether or not to participate. . 
 
Screening 
The screening interview will take place immediately after consenting in patients that had undergone 
an elective procedure and acute PCI patients who are up for it and well enough to answer questions. 
The remained of the acute patients, or if patients indicated they are not up to it, will be called at 4 
weeks follow-up to do screening interview. The screening interview takes five minutes to complete. 
 
Questionnaire data collection procedure: 

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Patients will receive multiple questionnaires, at right after PCI, 30 days post-PCI, 1 year post-PCI and 
then yearly for the following 10 years. Because of the high number of potential participants we are 
aiming at, a link will be sent to participants to a digital, web-based questionnaire. When participants 
explicitly ask for a paper version, we will comply with this request. When a questionnaire is not 
returned (through the web-based program) within 2 weeks after the measurement occasion, a 
reminder email is sent. Medical data of the patients participating in the questionnaire study will be 
obtained from the registry and the patient’s electronic medical record.  
 
Blood collection procedure: 
To be able to obtain the pre-PCI blood sample from the arterial sheath (right before catheter insertion), 
in all acute PCI patients this blood should be collected. After PCI, when still at the Cardiology inpatient 
ward, patients will be asked to participate in the study. When patients refuse, the blood collected pre-
PCI will be instructed to be destroyed. This is a common procedure, that also takes place for multiple 
studies in PCI patients in the Erasmus MC in Rotterdam. For the biomarker substudy, participants are 
asked to provide in total 3 blood samples, pre-PCI, after 30 days, and after 12 months post-PCI. When 
patients do not want to participate in the study, or blood sub study, the pre-PCI sample is destroyed. 
The 12 month sample c coincides with a regular clinic visits during which blood is already drawn.  
 
6. Outcome questionnaires 
 
Health complaints scale - The Health Complaints Scale consists of 12 somatic and 12 cognitive items 
answered on a 5 point Likert scale. Three somatic subscales (cardiopulmonary complaints, fatigue and 
sleep problems) and two cognitive subscales (health worries, disability feelings) can be identified. The 
questionnaire has been developed as an outcome measure in patients with coronary heart disease, 
and has demonstrated sensitivity to treatment in patients attending cardiac rehabilitation 24. 
  
MOS – General adherence: The questionnaire contains 4 general adherence questions asking whether 
the patient has complied with the doctor’s suggestions and treatment plan and the ease with which 
the patient had adhered on a 6-point Likert scale (1: None of the time – 6: All of the time).39 
 
MOS – Adherence behaviors: This questionnaire contains 15 adherence behaviors for which the 
patients should answer on a 6-point Likert scale to what extent (1: None of the time – 6: All of the 
time) they have adhered to these disease specific adherence behaviors (e.g. cutting down on stress in 
life, try to socialize more, exercise more often, take medication). 39 
 
Quality of life& health complaints (all measurement occasions) 
Satisfaction with life (SWLS), quality of life (WHOQOL-bref), Health complaints (HCS), Angina 
symptoms (SAQ) 
Table 1. Summary table questionnaire 
 

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#items 
Name 
Questionnaire 
Ref. 
Measurement 
occasions 
Personality 
 
 
 
Neuroticism/ Extraversion 
24 
EPQ-NE 
40 
T0, T3 
Type D 
14 
DS-14 
32 
T0, T1, T3 
Optimism 
10 
LOT-R 
 
T0, T3 
Mindfulness 
20 
FFMQ 
12 
T0, T1, T3 
Resilience 
15 
DRS 
 
T0, T3 
Cardiac self-efficacy 
10 
CSAQ 
41 
T0, T3, T4 
Trait anger 
10 
STAQ 
 
T0, T1, T2 
Hostility 
7 
CMHS 
42 
T1, T3, T4 
Mood 
 
 
 
Depression  
32 
PHQ-9 BDI-II 
20,29 
T0, T1, T2, T3, T4 
Anxiety 
7 
GAD-7 
26 
T0, T1, T2, T3, T4 
Negative mood state 
6 
GMS-12 
43 
T0, T1, T2, T3, T4 
Positive mood state 
6 
GMS-12 
43 
T0, T1, T2, T3, T4 
 
 
 
 
 
Emotion regulation 
 
 
 
Coping 
48 
CISS 
44 
T0, T1, T2, T3 
Psychological mindedness 
24 
BIPM 
37 
T0, T2, T4 
Worry 
16 
PSWQ 
45 
T0, T1, T2, T3, T4 
Chronic stress 
 
 
 
Life events scale 
28 
Levens-
gebeurtenissen 
21 
T0, T3, T4 
Effort-reward imbalance 
16 
ERI 
22 
T0¸ T3, T4 
Marital quality 
6 
MMQ6 
23 
T0, T3, T4 
PTSD 
22 
SRiP 
 
T0 T2 
Outcomes 
 
 
 
Health complaints 
22 
HCS 
24 
T0, T1, T3, T4 
Angina symptoms 
7 
SAQ-7 
46 
T0, T1, T3, T4 
Quality of Life 
26 
WHOQOL bref 
47 
T0, T1, T3, T4 
Behaviors 
 
 
 
Adherence 
22 
MOS adherence 
39 
T0, T1, T2, T3, T4 
Decision making 
 
 
 
 
Shared decision making 
9 
SDM-Q-9 
 
 

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6.1 Withdrawal of individual subjects 
Subjects can leave the study at any time for any reason if they wish to do so without any 
consequences. However, their clinical data will remain in the standard of care PCI registry, 
because this is bound by law. The investigator can decide to withdraw a subject from the 
study for urgent medical reasons, i.e. if a participant is too ill to fill out questionnaires or have 
their blood drawn. 
6.1.1 Specific criteria for withdrawal (if applicable) 
Patients will be withdrawn from the study when the cardiologist negative advices on 
participation.   
 
  
6.2 Replacement of individual subjects after withdrawal 
Patients will be included until the number of participants is reached necessary to obtain the 
desired effect size with sufficient statistical power. So, if participants drop out or withdraw 
from the study, additional patients will be recruited.  
 
6.3 Premature termination of the study 
Criteria for premature termination of the study: 
no one is willing to participate.  
 
 
7. SAFETY REPORTING 
7.1 Section 10 WMO event 
In accordance to section 10, subsection 1, of the WMO, the investigator will inform the subjects 
and the reviewing accredited METC if anything occurs, on the basis of which it appears that the 
disadvantages of participation may be significantly greater than was foreseen in the research 
proposal. The study will be suspended pending further review by the accredited METC, except 
insofar as suspension would jeopardise the subjects’ health. The investigator will take care that all 
subjects are kept informed.  
 
7.2 AEs, SAEs and SUSARs 
7.2.1 Adverse events (AEs) 
We will record procedures (PCI, CABG), implantations (ICD, pacemaker), myocardial infarction 
(MI) and mortality for the first 10 years after inclusion.  
7.2.2 Serious adverse events (SAEs) 
As the current research proposal does not involve an intervention but is observational in 
nature, adverse events due to disease progression will only be recorded and will not be 
separately reported. All adverse events that occur in the current PCI population within the first 
year post-PCI will also be reported to the national PCI registry.   
 

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8. STATISTICAL ANALYSIS 
Baseline characteristics will be described in means (SD) for continuous variables and in percentages 
(N) in case of categorized variables. Differences in baseline characteristics for example between 
participants that are and are not attending cardiac rehabilitation or between emotionally 
distressed and non-distressed participants are calculated using t-tests in case of continuous 
variables and using chi-square tests in case of categorized variables. When more than two 
categories are present, z tests will discriminate significant column differences, and appropriate 
Bonferroni corrections for multiple comparisons will be applied. Questionnaire scores will be 
calculated as described in the methods section above.  
 
Missing data: If on a questionnaire a few items are missing (between 100-75% of items filled out), 
items will be imputed by replacing the missing score with that subjects mean score. This means 
that only 75% of the questions within a questionnaire need to be filled out to be able to compute 
a total score.  
 
Answering the main objectives:  
Prediction of outcomes 
Multivariate logistic regression analysis and Cox proportional hazard 
models will be used to examine the long term predictive qualities of 
psychological and medical risk factors on complications, events, 
hospital admission and mortality. 
 
Validation  
 
 Exploratory and confirmatory factor analysis and reliability statistics 
will be used to validate the ESC psychosocial screening instrument 
 
Mechanisms 
 
Multiple regression analysis, mixed linear modelling and path analysis 
using structural equation modelling will be used to examine the 
interrelations between the various potential biological and behavioral 
mechanisms explaining the link between psychological risk factors and 
cardiovascular prognosis. Cluster analysis will be used to identify 
different patient profiles over the course of time based on the 
prospective biological and psychological data. 
Gender effects  
Moderation analysis will be used to examine the moderating effect of 
sex and gender.  
 
 
9. ETHICAL CONSIDERATIONS 
9.1 Regulation statement 
The PCI registry research project will be conducted according to the principles of the Declaration of 
Helsinki (2008) and in accordance with the Medical Research Involving Human Subjects Act (WMO), 
Dutch data protection act (Wbp) and the Code of ethics for psychologists (2007). 
 
9.2 Recruitment and consent 
Patients will be recruited in the Questionnaire study when they are admitted to the TweeSteden 
hospital for an elective or subacute PCI. Beforehand (a couple of days to a week before admission), 

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when the Heart team has decided that a PCI is necessary, the patient will receive a letter from his/her 
cardiologist informing him/her on the PCI Registry study. The letter explains that there is a main study 
consisting of questionnaires only, and that there will be substudies in the future in which a patient can 
participate as well. Patients may give consent for the main study, but may also give consent for added  
substudies. After study information has been given by the cardiologist and the patient is deemed 
eligible by the cardiologist, patients will be recruited by a junior researcher (paid by NWO) together 
with a specialized PCI nurse that guides all patients during the period preceding the PCI. Patients will 
have 3-4 days to consider their participation, or can decide immediately. The patient information letter 
and the informed consent are attached as separate documents.  
 
Acute PCI patients (patients that receive a PCI immediately after presentation at the ER with 
significant cardiac complaints or an MI) will be invited into the study after they have received the PCI, 
while still admitted at the hospital. Patients are informed about the study by their cardiologist or PCI 
nurse and receive an information letter and informed consent which they can return immediately or 
by mail in the week after the PCI. At the moment the patient has decided to participate,  an email link 
is sent for the first questionnaire or the paper questionnaire is handed to them in hospital or sent by 
mail. For the blood sub study in the acute patients, participating patients need to provide consent 
when still in hospital because of the timing of blood sampling.   
 
9.3 Benefits and risks assessment, group relatedness 
This is a non-therapeutic observation study. There is only a limited risk to participation. Filling out 
questionnaires about psychological symptoms may induce people to contemplate their own mental 
health. Importantly, the question about suicide, which is included in the depression questionnaire, has 
been shown not to induce more suicide events (e.g.,48). In case a person would answer that he/she is 
actively thinking about suicide, the coding will be broken, and the person will be contacted to offer 
help (e.g. contacting the GP for this person, or arranging a consultation with a psychologist).  
 
The benefits of participation are that by implementing the psychosocial risk factor screening 
instrument, psychosocial issues may be identified sooner, and appropriate care may be initiated 
sooner. Moreover, participation of the cardiology department of the TweeSteden hospital in this PCI 
registry may induce better adherence to the PCI guidelines, as the registry asks the cardiologists and 
nurses to better registration of the post-PCI treatment phase (rehabilitation, diet, lifestyle advice).  
 
9.4 Compensation for injury 
We would like to ask for dispensation from the statutory obligation to provide insurance, because 
participating in the study is considered a minimal risk. A reasoned request is attached to this proposal 
as a separate document. In accordance with article 7, subsection 6 of the WMO Tilburg University has 
a liability insurance covering the research activities of its employees.  
 
10. ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 
10.1 Handling and storage of data and documents 
Upon entry in the study, participants will receive a study number. All data collected for the study, will 
use this subject number instead of the patient’s name or hospital patient number. The study number 
consists of “CoRPS Project number”-“CoRPS Site number”-Study serial number” (xxxx-xxx-xxxx). 
Questionnaire data will be collected through CoRQuest, a digital questionnaire program, and medical 

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data will be recorded in a digital case record form. Digital data will be stored on a separate server using 
the patient’s study number as a unique identifier and linking pin to connect questionnaire and medical 
data. All other documents on paper (e.g., signed informed consents, questionnaires filled out on paper) 
will be stored in the CoRPS research institute archive for 15 years.  
 
10.2 Monitoring and Quality Assurance  
Study quality monitoring takes place using a digital application that was built by Spits research support 
(Tilburg University). With the “Patient Management System” monthly queries will be ran on study 
inclusion and attrition. Also, the PMS will keep a record of the completion of measurements so that at 
any time an overview is present of the completeness of data at all measurement occasions as well as 
the percentage of missing data.     
 
10.3 Amendments  
Amendments are changes made to the research after a favourable opinion by the accredited METC 
has been given. All significant amendments will be notified to the METC that gave a favourable opinion.  
 
10.4 Annual progress report 
The sponsor/investigator will submit a summary of the progress of the study to the accredited METC 
once a year. Information will be provided on the date of inclusion of the first subject, numbers of 
subjects included and numbers of subjects that have completed the trial, serious adverse events/ 
serious adverse reactions, other problems, and amendments.  
 
10.5 End of study report 
The investigator will notify the accredited METC of the end of the study within a period of 8 weeks. 
The end of the study is defined as the last patient’s visit. In case the study is ended prematurely, the 
investigator will notify the accredited METC within 15 days, including the reasons for the premature 
termination.  Within one year after the end of the study, the investigator will submit a final study report 
with the results of the study, including any publications/abstracts of the study, to the accredited METC. 
 
10.6 Public disclosure and publication policy 
The study design of the registry study and its substudies will be registered as an observational cohort 
study. The results from the current study will be published in international peer reviewed journals and 
will be presented at national and international conferences.  Patients will be informed on the results 
of the study by a patient newsletter and by information on the CoRPS patient website 
(www.tilburguniversity.edu/corps). 
 
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40. Denollet J, Kupper N. A concise version of the GMS12 submitted. 
41. Kupper N, Denollet J. Social anxiety in the general population: introducing abbreviated versions of SIAS and 
SPS. Journal of affective disorders 2012;136:90-8. 
42. Endler NS, Parker JDA. Multidimensional assessment of coping: A critical evaluation. Journal of Personality 
& Social Psychology 1990;58:844-54. 
43. Jones P, Chan P, Gosch K, et al. The SAQ-7: A Short Version of the Seattle Angina Questionnaire Circ 
Cardiovasc Qual Outcomes 2013; 6:A54. 
44. Skevington SM, Lotfy M, O'Connell KA. The World Health Organization's WHOQOL-BREF quality of life 
assessment: psychometric properties and results of the international field trial. A report from the WHOQOL 
group. Qual Life Res 2004;13:299-310. 
45. Mathias CW, Michael Furr R, Sheftall AH, Hill-Kapturczak N, Crum P, Dougherty DM. What's the harm in 
asking about suicidal ideation? Suicide Life Threat Behav 2012;42:341-51. 
46. Stewart DE, Abbey SE, Shnek ZM, Irvine J, Grace SL. Gender differences in health information needs and 
decisional preferences in patients recovering from an acute ischemic coronary event. Psychosom Med. 
2004;66(1):42-8. 
 

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47. Authors/Task Force Members, Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney 
MT, Corrà U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FD, Løchen ML, Löllgen H, Marques-Vidal P, Perk J, 
Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WM; 
Additional Contributor: Simone Binno (Italy); Document Reviewers:, De Backer G, Roffi M, Aboyans V, Bachl N, 
Bueno H, Carerj S, Cho L, Cox J, De Sutter J, Egidi G, Fisher M, Fitzsimons D, Franco OH, Guenoun M, Jennings C, 
Jug B, Kirchhof P, Kotseva K, Lip GY, Mach F, Mancia G, Bermudo FM, Mezzani A, Niessner A, Ponikowski P, 
Rauch B, Rydén L, Stauder A, Turc G, Wiklund O, Windecker S, Zamorano JL. 2016 European Guidelines on 
cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of 
Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by 
representatives of 10 societies and by invited experts): Developed with the special contribution of the 
European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol. 
2016;23(11):NP1-NP96. 
 
 

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 APPENDIX I - ESC Prevention guideline Psychosocial Risk Factor Screener 
 
 
Name: ……………………………………………………………………… 
Patient ID: ……………………………………. 
What 
is 
your 
highest 
educational degree? 
  University, Higher vocational 
  Intermediate vocational 
  Secondary education 
  Primary education (or less) 
What is your 
marital status? 
  Married or living together 
  Partner not living together 
  Single  
  Divorced, widowed 
What is your work status? 
 Working 
 Unemployed / In training 
 Pensioner 
 Household work 
 
 
 
Not at all 
Somewhat 
Pretty 
much 
Very 
much 
11.1 Over the past 2 weeks, have you been bothered by any of the following problems? 
Do you feel down, depressed, and hopeless? 
 
 
 
 
Have you lost interest and pleasure in life? 
 
 
 
 
Do you, at times, suddenly feel fear or panic?  
 
 
 
 
Are you unable to stop or control worrying? 
 
 
 
 
Do you feel tired, or have a lack of energy? 
 
 
 
 
11.2 Lately, have you experienced any of the following stressors? 
Do you feel burdened by your working conditions? 
 
 
 
 
Do you receive insufficient appreciation for your work? 
 
 
 
 
Do you lack a close confidant? 
 
 
 
 
Do you have family problems? 
 
 
 
 
Do you suffer from nightmares or recurrent unpleasant memories? 
 
 
 
 
11.3 In general, how would you describe yourself? 
Do you often feel anxious, irritable, or depressed? 
 
 
 
 
Do you tend to take a gloomy view of things? 
 
 
 
 
Do you find it hard to start a conversation because you don’t know what 
to talk about? 
 
 
 
 
Do you consider yourself to be a closed kind of person? 
 
 
 
 
Do you tend to bottle up your anger? 
 
 
 
 
Are you bothered by outbursts of anger? 
 
 
 
 
Do you find it hard to trust people? 
 
 
 
 
Do you feel that you often are told what to do by less knowledgeable 
people? 
 
 
 
 
11.4 Have you experienced any of the following? 
Did you experience 1 or more negative events in your life that still 
produce strong & negative feelings in the present? 
 yes, 
namely…………………………………………………………………………………
……………………………………………………………. 
 no 
Have you ever been told you had a mental disorder (such as depression 
etc.) or were treated by a psychiatrist or a psychologist?" 
 yes, namely…………………………… 
………………… 
 no 

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