Chronic Coronary Syndrome in Swedish Primary Care
Phase: NA
Conditions: Coronary Artery Disease
Sponsor: Region Östergötland

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
1 
 
 
Study Protocol 
Chronic coronary syndrome in Swedish primary care (COSPRI) 
A cluster-randomized study on a single-visit package investigation versus routine sequential 
investigation for chronic coronary artery disease conducted in Swedish primary health care. 
 
NCT ID:2022-04416-01 
 
 
Document revision history 
Issue 
Summary of change 
According to approved amendment 2024-01599-02:  
Change of principal investigator 
Health economic analyses after one and five years 
Some clarifications in the text and Figure 1 
 
01 
01.1 
01.2 
New document March 10, 2023 
Updated document January 31 2025 
Updated document Januari 21 2026 
 
 
Research team 
Principal investigator: 
Fredrik Iredahl (is the coordinating PI from March 27, 2024) 
Researchers: 
Staffan Nilsson was the PI until March 26, 2024 
Jan Engvall 
Sofia Sederholm Lawesson 
Carl Johan Östgren 
Lars Bernfort 
Mats Fredriksson 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
2 
 
Silvia Mainardi 
Johan Lööf 
PhD-students within the study: 
Erik Stertman 
Fade Gabro 
Research nurse: 
Liselott Yxne 
 
 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
3 
 
1. Background 
In primary health care patients with chest symptoms are common. In many cases the cause is benign 
but chronic coronary artery disease (CAD) must often be considered [1, 2]. In the clinical work, 
evaluation of symptoms and risk factors are fundamental for a plausible working diagnosis and to judge 
if any further investigation is needed. The probability of CAD for a person of a certain age, sex and 
character of chest symptoms, scored from 0-3, i.e. pretest probability (PTP) for CAD, is substantially 
lower now than it was a decade ago in western countries [3, 4]. Consequently, recent European 
guidelines recommend that further investigation to rule out CAD may be omitted if the risk for CAD is 
judged to be low (PTP<15 %) and there are no further cardiovascular risk factors [4]. If further 
investigation is needed in the low-risk group, coronary computed tomography angiography (CTA) is 
preferable [4]. When the risk for CAD is judged to be intermediate (PTP> 15 %) an imaging investigation 
is advocated instead of the well-established exercise stress bicycle test. A much-used imaging test is 
myocardial perfusion scan in which an exercise stress bicycle test is performed, with the addition of an 
intravenous injection of a small amount of radioactive tracer, whereafter the myocardial blood flow is 
demonstrated by imaging. Sensitivity for myocardial perfusion scan to detect significant CAD is 87 % 
(95 % CI 83–90) in comparison with exercise stress bicycle test where it is only 58 % (95 % CI 46–69). 
Specificity is 70 % (95 % CI 63–76) and 62 (95 % CI 54–69), respectively [5]. However, the exercise stress 
bicycle test can reveal indirect signs of myocardial ischemia, is reasonable in price, easy to perform 
and available in many clinics and hospitals. It is since long the first-line method for referral from the 
primary care setting in Sweden. If the result from the exercise stress bicycle test is inconclusive, the 
work-up should be continued, e.g. with myocardial perfusion scan. An echocardiogram is often 
performed as well to evaluate the condition of the myocardium, heart valves and left ventricular 
ejection fraction. This stepwise or sequential clinical work-up strategy is well known and reasonable in 
general practice where patients in general have a low prevalence of serious diseases compared to 
organ specialist clinics.  Since June 2021 in Region Östergötland, Sweden, (471 912 inhabitants, 2022) 
coronary CTA is recommended if further investigation is deemed necessary in patients with a low risk 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
4 
 
of CAD (PTP< 15 %) in primary care. For patients with intermediate risk of CAD (PTP> 15 %) exercise 
stress bicycle test is still the first-line choice. Echocardiography may also be considered. 
There may be advantages if the imaging investigation, myocardial perfusion scan and echocardiogram 
is performed on a single visit. In addition, a CT scan of the heart to determine coronary artery 
calcification (CAC) score is easy to perform on the same visit and adds only a small amount of radiation. 
The CAC-score has been shown to be an independent predictor of future cardiovascular events and is 
useful for reclassification of cardiovascular risk based on traditional risk factors like age, cholesterol 
levels and smoking habits [6]. CAC score may be used for reclassification of cardiovascular risk based 
on traditional risk factors like age, cholesterol, blood pressure and smoking [7]. 
Furthermore, a clear and coherent answer to the referring GP on all three investigations, myocardial 
perfusion scan, echocardiogram and CT scan of the heart may provide a completer and more 
illustrative basis for clinical decision-making. For the individual patient it is probably an advantage to 
get a thorough investigation done at one single visit and possibly a faster and more valid statement 
from the investigations by the GP. 
On the other hand, if many advanced investigations are done unnecessarily, expenses and exposure 
to radiation will increase unjustifiably. Possibly there is also a risk of medicalization and to create 
worries for future cardiovascular events communicating the CAC-score to people that has not asked 
for the information. 
In order to get a faster and more complete basis for the evaluation of CAD in primary care patients 
with an intermediate (PTP> 15 %) risk we created a package investigation comprised of myocardial 
perfusion scan, echocardiogram and CT scan of the heart on a single visit. The results from myocardial 
perfusion scan will be written according to national Swedish guidelines and communicated to the 
referring GP together with results from echocardiogram and CAC-scoring as a coherent answer. 
Moreover, registration of heart sounds followed by risk calculation by a technical device Cadscore® 
will be performed but only for scientific analyzes and not given as a clinical answer [8]. 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
5 
 
In this study we aim to compare the standard routine sequential investigation for detecting CAD with 
a single-visit package investigation. 
2. Objectives and research questions 
The objective of the study is to compare the effects of a coherent ischemia investigation on a single 
visit with the current clinical sequential routine for patients in primary care with a medium probability 
(PTP> 15%) of chronic CAD regarding: 
Research questions: 
Is there a significant difference between study groups 
• 
Regarding waiting time for invasive coronary angiography or for the participants to be given 
results from completed non-invasive myocardial investigation? 
• 
Regarding the outcome, connected to the main symptom i.e. chest pain/discomfort or 
dyspnoea? 
• 
The costs per patient? 
• 
The frequency of given advice on lifestyle changes? 
• 
Health related quality of life, self-reported physical activity, physical fitness, dietary habits, 
mental symptoms and heart related anxiety on the day of inclusion, after 1, 3 and 5 years? 
• 
The prescription of and adherence to drugs for CAD prevention 2 years before the day of 
inclusion, 2 and 5 years thereafter? 
• 
The incidence of cardiac events after 2 and 5 years? 
3. Outcome measures 
3.1 Primary outcome measure 
The waiting time, counted in days, begins on the date when the results of the package investigation 
(package investigation group), exercise bicycle stress test (standard investigation group) are 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
6 
 
approved and immediately available for the physician at the PHCs. It extends until the day for 
performance of invasive coronary angiography or until the communication of results, from the 
completed non-invasive myocardial ischemia investigation to the trial participant (patient), as 
reported in medical records. It is important to note that waiting time for the initial investigation will 
not be included in this measurement (Figure 1). 
3.2 Secondary outcome measure 
Time points for assessment of secondary outcome measures are described in Figure 1. 
• 
Presence of pathological q-waves on resting ECG. 
• 
Reversible ischemia, ST-depression provoked by exercise. 
• 
Signs of reversible ischemia on any test 
• 
Radiation per patient measured in millisievert (mSv). 
• 
Sick leave (days). 
• 
Physical activity will be measured by two categorical questions asking for level of physical 
activity [9]. 
• 
Dietary habits will be measured by five categorical questions about consumption of fruit, 
vegetables, snacks and soft drinks during the last week [10]. 
• 
Heart focused anxiety will be measured by the Cardiac Anxiety Questionnaire – CAQ An 18-
item scale [12]. 
• 
Generalized anxiety will be measured by the Brief Measure for Assessing Generalized Anxiety 
Disorder - GAD-7 A seven item scale [13]. 
• 
Depression symptoms will be measured by the Patient Health Questionnaire - PHQ-9 
Maximum score 27 [14]. 
• 
Sleep quality will be measured by The Pittsburgh Sleep Quality Index – PSQI A 19-item scale 
which assesses sleep quality and disturbances over a 1-month time interval [15]. 
• 
Physical fitness will be measured by The International Fitness Scale – IFIS A 5-item scale [16]. 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
7 
 
• 
Questions on being a professional worker or not, working hours per week, smoking habits 
and passive smoking, by a questionnaire constructed for the study, the COSPRI 
questionnaire. 
• 
Dental health will be explored by a 5-item questionnaire constructed for the study. 
• 
Alcohol consumption will be measured by the Alcohol Use Disorders Identification Test - 
AUDIT. Score range: 0-40. (WHO-publications 2001) [18]. 
• 
Coffee consumption will be measured with questions about how often and how many cups 
of coffee are consumed. 
• 
Major adverse cardiovascular events (MACE). Data from register SWEDEHEART, National 
Patient Register and National Cause of Death Register [19-21]. 
• 
Adherence to prescribed cardioprotective drugs. Data from the National Prescribed Drug 
Register [22]. 
Health-related quality of life will serve as the outcome in the health economic analysis and will be 
measured by EQ-5D-5L and RAND-36 Swedish versions to estimate quality-adjusted life-years (QALYs) 
[11, 17]. The incremental costs for package- vs. standard investigation will be divided by incremental 
QALYs for the same comparison to get the incremental cost-effectiveness ratio (ICER), i.e., cost per 
QALY, of package investigation vs. standard investigation. 
4. Project description 
4.1 Design 
A cluster randomized study in Region Östergötland (471 912 inhabitants, 2022) in southeast Sweden. 
All currently existing 47 (January 2023) primary health care centers in the region are invited to 
participate. There are three hospitals in the Region Östergötland, one university hospital with a 
Physiology clinic and Cardiac clinic, a non-university hospital with Physiology clinic and a Cardiac clinic 
and a smaller hospital with an internal medicine clinic serving the nearby primary health care centers 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
8 
 
with cardiac consultations. In addition, there is a privately run cardiac specialist clinic in one of the 
cities serving some primary health care centers with cardiac consultations. Almost all inhabitants in 
the region are registered at one of the 47 primary health care centers. 
4.2 Randomization 
The management of each primary health care center must accept randomization to either coherent 
ischemia investigation on a single visit “package investigation” or current clinical sequential routine 
“standard investigation” for applicable patients. When enough primary health care centers have 
accepted to participate the centers will be stratified based on the number of listed inhabitants on each 
of the primary health care centers and randomized 1:1 to package or standard investigation.  
Randomization will be performed by a statistician at Forum Östergötland, a support function for clinical 
translational research at Linköping University and Region Östergötland. The goal is to include at least 
20 primary health care centers in total. 
4.3 Masking/blinding 
No masking or blinding of participating physicians or study participants. 
4.4 Registration 
The study is registered at clinicaltrials.gov. 
5. Subjects 
5.1 Selection and recruitment 
Patients who seek primary care for symptoms judged to be compatible with a medium probability 
(PTP> 15) for symptomatic CAD, without exclusion criteria, at any of the participating primary health 
care centers will be informed about the possibility to participate in the study. 
5.2 Number of research participants 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
9 
 
The sample size calculation is based on a comparison of the two mean waiting time (days) values, based 
on historical data, in a cluster randomized design where the clusters are the PHCs. We have used 18 
clusters for the calculation, and we estimate the within cluster correlation to be 0.1. Since the size of 
the clusters differ in size, we included a coefficient of variation of 0.46, based on the actual sizes of the 
PHCs. We have assumed the mean number of waiting time to be 37 days in the standard investigation 
group and 22 days in the package group with a standard deviation of 39 and 16, respectively. This 
assumption is based on, historical data on waiting times and a regional dialogue between 
representatives from Primary health care, Clinical Physiology- and Cardiology Departments prior the 
start of the study. With these assumptions, we estimate, with a power of 80% and a significance level 
set to 5%, that we need 416 participants, 208 per group. We expect that there will be some dropouts, 
so we increase the number of participants to 250 in each group. 
 
5.3 Inclusion criteria 
• 
Patients who seek primary care for symptoms judged to be compatible with a medium 
probability (PTP> 15) for symptomatic CAD at any of the participating primary health care 
centers. 
5.4 Exclusion criteria 
• 
Suspicion of acute coronary syndrome when care is sought. 
• 
Previously diagnosed acute myocardial infarction. 
• 
Revascularization with PCI/CABG. 
• 
Proven reversible ischemia according to myocardial scintigraphy. 
• 
Left Bundle Branch Block (LBBB). 
• 
Ventricular pacemaker. 
• 
Age below 18 years 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
10 
 
• 
People whose meaning due to illness, mental disorder, weakened state of health or any 
other similar condition cannot be obtained, to be included in a research project. 
• 
Insufficient understanding of spoken and written Swedish language. 
 
Results will be reported according to CONSORT 2010 - extension to cluster randomized trials. 
6. Interventions 
Participants in the package investigation group will be subject to investigation by: 
1.Resting ECG, 
2.Evaluation of risk according to PTP-table. 
3.Echocardiography. 
4.Exercise stress bicycle test (secondarily drug provocation) with injection of isotope for myocardial 
scintigraphy. 
5.Scanning for myocardial perfusion 
6.CAC-scoring with CT. 
7. Sound registration with Cadscore® and added risk calculation. Recording of cardiac diastolic 
sounds enabling the calculation of a risk score. 
Participants in the standard investigation group will be subject to investigation by: 
1.Resting ECG 
2.Evaluation of risk according to PTP-table. 
3. Echocardiography. 
4.Exercise stress bicycle test. 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
11 
 
If judged to be needed according to clinical indication sequentially completed by: 
Exercise stress bicycle test (secondarily drug provocation) with injection of isotope for myocardial 
scintigraphy and/or coronary CTA. In addition, cardiac examinations done with other modalities 
chosen on clinical grounds will be examined in the study. 
 
7. Measurements/variables 
 
STUDY PERIOD 
 
Enrolment 
Allocation 
POST ALLOCATION 
Close-
out 
 
PHC 
enrolment 
 
1 year 
follow 
up 
2 
years 
follow 
up 
3 
years 
follow 
up 
5 years 
follow up 
 
Time point, 
(months relative to 
randomization) 
-4- -0 
0 
12 
24 
36 
60 
60 
ENROLMENT 
 
PHC consent (for 
trial) 
X 
 
 
 
 
 
 
Patient’s consent 
for study 
participation 
 
X 
 
 
 
 
 
ALLOCATION 
 
PHC randomisation 
X 
 
 
 
 
 
 
INTERVENTION 
 
Intervention and 
comparator arm: 
 
 
 
 
 
 
 
Resting  ECG 
 
X 
 
 
 
 
 
Riskevaluation 
based on PTP 
 
X 
 
 
 
 
 
Echocardiograpy 
 
X 
 
 
 
 
 
Exercise bicycle 
stress test 
 
X 
 
 
 
 
 
Intervention arm: 
 
 
 
 
 
 
 
SPECT 
 
X 
 
 
 
 
 
CT scan for CAC 
scoring 
 
X 
 
 
 
 
 
 
CadScore 
 
X 
 
 
 
 
 
ASSESSMENT 
 
MACE 
 
 
 
X 
 
X 
X 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
12 
 
Pathological q-
waves on resting 
ECG 
 
X 
 
 
 
 
 
Signs of reversible 
ischemia on any 
test 
 
X 
 
 
 
 
 
Waiting time (days)  
 
X 
 
 
 
 
Previuos medical 
history 
 
 
X 
 
 
 
 
Clinical conclusion 
of cardiac 
investigations 
 
 
X 
 
 
 
 
Laboratory tests 
 
 
X 
 
 
 
 
Cardiovascular 
prevention: lipid-
lowering, platelet-
inhibiting or oral 
anticoagulating 
drugs and 
counseling 
 
 
X 
 
 
 
 
Cardiopulmonary 
examinations 
related to ongoing 
investigation 
 
 
X 
 
 
X 
X 
Adherence to 
prescribed 
cardiovascular 
drugs 
 
 
 
X 
 
X 
X 
Number of 
contacts with 
primary care, 
hospital out-
patient clinics and 
in-hospital care 
 
 
X 
 
 
X 
X 
Radiation exposure 
 
 
X 
 
 
X  
X 
Family history of 
cardiovascular 
diseases 
 
X 
X 
 
X 
X 
X 
Smoking habits 
 
X 
X 
 
X 
X 
X 
Alcohol 
consumption: 
AUDIT 
 
X 
X 
 
X 
X 
X 
Coffee 
consumption 
 
X 
X 
 
X 
X 
X 
Physical activity 
 
X 
X 
 
X 
X 
X 
Physical fitness: 
IFIS 
 
X 
X 
 
X 
X 
X 
Dietary habits 
 
X 
X 
 
X 
X 
X 
Heart focused 
anxiety, CAQ 
 
X 
X 
 
X 
X 
X 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
13 
 
Generalized 
anxiety: GAD-7 
 
X 
X 
 
X 
X 
X 
Depression 
symptoms: PHQ-9 
 
X 
X 
 
X 
X 
X 
Sleep quality: PSQI 
 
X 
X 
 
X 
X 
X 
Dental health 
 
X 
X 
 
X 
X 
X 
Health related 
quality of life: EQ-
5D-5L, RAND-36 
 
X 
X 
 
X 
X 
X 
 
Figure 1 
Schedule of enrolment, intervention and assessment in the Chronic cOronary Syndrome in 
Swedish PRImary care (COSPRI) study. PHC = Primary Healthcare Center; ECG = 
electrocardiogram; PTP = Pre-test Probability; SPECT = Single photon emission computed 
tomography; CT = Computed Tomography; CAC = Coronary Artery Calcification; CadScore = 
is an acoustic risk score; MACE = Major Adverse Cardiovascular Events; AUDIT = Alcohol Use 
Disorders Identification Test; IFIS = International Fitness Scale; CAQ = Cardiac Anxiety 
Questionnaire; GAD-7 = Generalized Anxiety Disorder; PHQ-9 = Patient Health Questionnaire; 
PSQI = Pittsburgh Sleep Quality Index; EQ-5D-5L = European Quality of Life 5 Dimensions 5 
Level Version. 
 
 
 
8. Statistical methods 
Reference to statistical analyzes plan (SAP) 
9. Data collection 
One year after the day of inclusion all participants’ computerized medical records will be reviewed and 
data entered a pre specified digital form RedCAP©. These data are about at what date an answer of 
the CAD investigation is communicated to the research participant on the result of the CAD-
investigation, current diseases like hypertension, previous stroke or TIA, type 2 diabetes, laboratory 
results, creatinine, cholesterol, HBA1C and NT-proBNP and sick leave during study time. Notes about 
cardio preventive lifestyle counseling found in the medical records are also entered in RedCAP©. 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
14 
 
Coronary CTA results if any, for all research participants and whether myocardial perfusion scan is 
performed is noted for the standard investigation group. Moreover, any X-ray or MRI investigations of 
the upper part of the body excluding head or upper extremities and the results noted as normal, 
difficult to assess or clearly pathological is entered in RedCAP©. Number of visits, telephone calls and 
video consultations by the participant to the primary care health center or cardiology clinic are also 
entered as well as any in-hospital care and for what diagnosis. 
 
Data will be retrieved from the National Patient Register, the Cause of Death Register run by the 
National Board of Health and Welfare and SWEDEHEART run by Uppsala Clinical Research Center (UCR) 
to construct a major cardiovascular event MACE. Further, data will be retrieved from the National 
Prescribed Drug Register run by the National Board of Health and Welfare to follow prescription of and 
purchased cardioprotective drugs and from Statistics Sweden about days on sick leave. 
10. Informed consent 
Detailed information about the study will be sent to the research participants together with 
appointment for package investigation or stress bicycle test and echocardiography (standard 
investigation) from one of the two Physiology clinics. At the Physiology clinic the research participants 
are asked to give written informed consent to participate in the study meaning questionnaires on the 
day of inclusion, after 1, 3 and 5 years, review of medical records and retrieval of data from Swedish 
National registries. The research participants must be given full and adequate oral and written 
information about the study, its purpose, possible risks and benefits. Research participants must also 
be informed that they are free to discontinue their participation in studies at any time without having 
to give a reason. The research person must be given the opportunity to ask questions and be allowed 
time to consider the information provided. A copy of the research participant information and the 
signed consent is provided to the research participant. The research participant's signed and dated 
informed consent must be obtained before performing any study-specific activity in the study. 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
15 
 
11. Adverse events 
Serious adverse event (SAE) is defined as, clinically diagnosed myocardial infarction, deaths 
by any cause or hospitalization for heart failure. Adverse event (AE) hospitalization for 
increased chest pain, indirectly diagnosed myocardial infarction, e.g. by pathologic q-wave. 
All members af the study staff at the participating Physiology clinics or privately-run 
cardiologist consultant are encouraged to report any SAE or AE of which they become aware 
to the steering committee. 
Towards the end of time period for inclusion of study participants we are planning for an 
adjudication committee of independent researchers tasked with determining the prevalence of 
MACE in both study groups i.e. package investigation or standard investigation, respectively. 
12. Data monitoring and research management 
Forum Östergötland, a support function for clinical translational research at Linköping university will 
do a startup check of the study. They will go through and see that all documentation such as permits, 
agreements and routines around storage and archiving is properly in place at sites taking part in the 
study and that good clinical practice (GCP) is followed. 
When the first 20 participants are included in the study, we will thoroughly analyze inclusion procedure 
at the Physiology clinics in Linköping and Norrköping and at the privately run cardiac specialist clinic, 
collection of data from questionnaires answered by participants and data manually collected by review 
of medical records and noted in the RedCAP©-CRF. 
Data retrieved from SWEDEHEART, National Patient Register, National Prescribed Drug Register, 
National Cause of Death Register and Statistics Sweden will not be monitored by Forum Östergötland. 
13. Data management plan 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
16 
 
Research persons participating in the study are coded with specific research person numbers. All 
research persons are registered on a research person identification list (code list) which links the 
research person's name and social security number with a research personal number. Region 
Östergötland is responsible for personal data. 
Pseudonymized record review (CRF) and survey data will be collected, entered in RedCAP© and 
stored on a server at Linköping university. Only authorized persons can log in to RedCAP© and the 
login is through two-step verification. Code list is stored on separate digital medium at the head of 
research, Region Östergötland. Once the data collection is complete, the data is downloaded from 
the RedCAP© server and stored in a secure platform at Linköping university. All image material is 
saved according to clinical routine and data for research purposes is saved in pseudonymised 
condition. Images are saved digitally. Individuals cannot be identified based on the image material. In 
Cadscore®, information about age, gender and symptoms is entered. Audio recording is performed 
which results in summation of probability of disease on a scale of 0-100. The audio recording itself is 
not saved. Image and supplementary functional data, blood pressure, pulse, pain response, grading 
of effort from myocardial perfusion scan, cycle work tests and echocardiography are saved in Region 
Östergötland's clinical databases and during analysis they are exported via pseudonymization 
equipment to the research database at the Centre for Medical Imaging Science and Visualization 
(CMIV). Code key is saved on a separate digital medium at the head of research, Region 
Östergötland. 
14. Design and testing of the database 
Control of the data set (RedCAP© form and variables) and that the content corresponds to the needs 
of the study must be done by the responsible researcher before the start of the study. The data must 
also be tested for export so that the collected research data corresponds to the study 
protocol/research plan. Variable list is extracted from the RedCAP© system and saved. 
All testing of the study database must be carried out before the start of the study. 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
17 
 
15. Updating the database 
Changes and amendments should be avoided. Inevitable changes and amendments must be planed 
together with Forum Östergötland. 
16. Closure of database 
When the study is finished and the data is monitored, the database is closed. After monitoring and 
after all questions have been resolved or, in cases where the question has not been resolved, 
commented on, the data can be exported from the system to the responsible researcher. This file 
then becomes a "clean file". 
This file must be archived together with other study material. Copies from this file are then used for 
data analysis. 
17. Management of source data 
Source data refers to:  
• 
Informed consents 
• 
Data from patient records 
• 
Data registered directly in RedCAP©. 
• 
Images, supplementary functional data and Cadscore® data. 
The source data must be available during the ongoing study and archived according to the archiving 
plan.  
18. Archiving 
Research data will be archived for at least 10 years and cleared out according to current routine in 
the Region Östergötland. 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
18 
 
19. Time frame 
Activity 
Date (yyyy—mm-dd) 
First study participant 
2023-05-01 
Inclusion of last study participant  
2027-12-31 
Retrieval of imaging data 
2029-05-01 
Retrieval of last questionnaire data 
2033-04-30 
Retrieval of last data from Swedish national 
registries  
2033-04-30 
 
20. Policy for publications 
Policy for authorship is based on four criteria recommended by International Committee of Medical 
Journal Editors (ICMJE): 1. Substantial contributions to the conception or design of the work; or the 
acquisition, analysis, or interpretation of data for the work; AND 2. Drafting the work or revising it 
critically for important intellectual content; AND 3. Final approval of the version to be published; 
AND 4. 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.  
Those who do not meet all four criteria for authorship may be acknowledged e.g. for acquisition of 
funding, administrative support, statistical advising or collection of data. 
21. References 
1. 
Bosner S - Becker, A., et al., - Chest wall syndrome in primary care patients with chest pain: 
presentation, associated features and diagnosis. Fam Pract, 2010. 27(4): p. 363-9. 
2. 
Hoorweg, B.B., et al., Frequency of chest pain in primary care, diagnostic tests performed and 
final diagnoses. Heart, 2017. 
3. 
Montalescot, G., et al., 2013 ESC guidelines on the management of stable coronary artery 
disease: the Task Force on the management of stable coronary artery disease of the European 
Society of Cardiology. Eur Heart J, 2013. 34(38): p. 2949-3003. 

COSPRI – Study Protocol 
Issue 1.2 Date 17-Dec-2025 
19 
 
4. 
Knuuti, J., et al., 2019 ESC Guidelines for the diagnosis and management of chronic coronary 
syndromes. Eur Heart J, 2020. 41(3): p. 407-477. 
5. 
Knuuti, J., et al., The performance of non-invasive tests to rule-in and rule-out significant 
coronary artery stenosis in patients with stable angina: a meta-analysis focused on post-test 
disease probability. Eur Heart J, 2018. 39(35): p. 3322-3330. 
6. 
Budoff, M.J., et al., Ten-year association of coronary artery calcium with atherosclerotic 
cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA). Eur 
Heart J, 2018. 39(25): p. 2401-2408. 
7. 
Nasir, K., et al., Implications of Coronary Artery Calcium Testing Among Statin Candidates 
According to American College of Cardiology/American Heart Association Cholesterol 
Management Guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol, 
2015. 66(15): p. 1657-68. 
8. 
Winther, S., et al., Diagnostic performance of an acoustic-based system for coronary artery 
disease risk stratification. Heart, 2018. 104(11): p. 928-935. 
9. 
Olsson, S.J., et al., Categorical answer modes provide superior validity to open answers when 
asking for level of physical activity: A cross-sectional study. Scand J Public Health, 2016. 44(1): 
p. 70-6. 
10. 
Henriksson, H., et al., MINISTOP 2.0: a smartphone app integrated in primary child health 
care to promote healthy diet and physical activity behaviours and prevent obesity in 
preschool-aged children: protocol for a hybrid design effectiveness-implementation study. 
BMC Public Health, 2020. 20(1): p. 1756. 
11. 
Ohlsson-Nevo, E., et al., The Swedish RAND-36: psychometric characteristics and reference 
data from the Mid-Swed Health Survey. J Patient Rep Outcomes, 2021. 5(1): p. 66. 
12. 
Eifert, G.H., et al., The cardiac anxiety questionnaire: development and preliminary validity. 
Behav Res Ther, 2000. 38(10): p. 1039-53. 
13. 
Spitzer, R.L., et al., A brief measure for assessing generalized anxiety disorder: the GAD-7. 
Arch Intern Med, 2006. 166(10): p. 1092-7. 
14. 
Hansson, M., et al., Comparison of two self-rating scales to detect depression: HADS and 
PHQ-9. Br J Gen Pract, 2009. 59(566): p. e283-8. 
15. 
Buysse, D.J., et al., The Pittsburgh Sleep Quality Index: a new instrument for psychiatric 
practice and research. Psychiatry Res, 1989. 28(2): p. 193-213. 
16. 
Ortega, F.B., et al., The International Fitness Scale (IFIS): usefulness of self-reported fitness in 
youth. Int J Epidemiol, 2011. 40(3): p. 701-11. 
17. 
Devlin, N.J. and R. Brooks, EQ-5D and the EuroQol Group: Past, Present and Future. Appl 
Health Econ Health Policy, 2017. 15(2): p. 127-137. 
18. 
AUDIT (Alcohol Use Disorders Identification Test). 2018  [cited 2022; Available from: 
https://www.socialstyrelsen.se/kunskapsstod-och-regler/omraden/evidensbaserad-
praktik/metodguiden/audit-alcohol-use-disorders-identification-test/. 
19. 
SWEDEHEART. 2022  [cited 2022 2022-01-26]; Available from: 
https://www.ucr.uu.se/swedeheart/start-scaar. 
20. 
National Patient Register. [Web Page] 2022 2022-01-14 [cited 2023 2023-03-02]; Available 
from: https://www.socialstyrelsen.se/en/statistics-and-data/registers/national-patient-
register/. 
21. 
National Cause of Death Register [Web Page] 2019-10-18 [cited 2023 2023-03-02]; Available 
from: https://www.socialstyrelsen.se/statistik-och-data/register/dodsorsaksregistret/. 
22. 
The Swedish Prescribed Drug Register. 2021  [cited 2021 2021-11-16]; Available from: 
https://www.socialstyrelsen.se/en/statistics-and-data/registers/national-prescribed-drug-
register/.