Cordicareone07032005.pdf

CORDICARE 1 / SINOPE STUDY: Version 07.03.2005


Investigators

Michel J. Romanens, MD
Protective Medicine Foundation (Vice President)
and
Head Non-Invasive Cardiology
RODIAG Diagnostic Centers
CH- 4600, Olten, Switzerland
[email protected]
André R. Miserez, MD
Protective Medicine Foundation (President)
c/o diagene gmbh, Kägenstrasse 17
4153 Reinach (BL)
Head, Cardiovascular Risk Clinic
Medical University Clinics
4101 Bruderholz (BL)
[email protected]

CORDICARE 1 / SINOPE STUDY: Version 07.03.2005

CONTENTS

1. Study center and number of subjects planned
2. Study period Phase of development
3. Summary
4. Rationale
5. Study Objectives
6. Study Organization
7. Hypothesis
8. Duration and Synopsis
9. Institutional Review
10.Methodology
11.Safety Issues
12.Description of sub studies
13.Patient Confidentiality
14.Data Analysis
15.Disclosure of Data and Publication
16.Investigators Approval
17.Funding
18.Budget
19.Appendices
- Appendix 1: Inseratetext Version 07.03.2005)
- Appendix 2: Websitentext (noch nicht generiert)
- Appendix 3: Written informed consent form (Version 07.03.2005)
- Appendix 4: Patients Questionnaire form (Version 07.03.2005)
- Appendix 5: German description of the study (Version 07.03.2005)
- Appendix 6: The CORDICARE Programs (Version 07.03.2005)
- Appendix 7: Calculations of vascular risk (Version 07.03.2005)
20.References

CORDICARE 1 / SINOPE STUDY: Version 07.03.2005


1. Study center and number of subjects planned
This study will be conducted in approximately 5,000 male and female subjects re-
cruited from Northwestern Part of Switzerland in the Study Center in Olten

2. Study period Phase of development
Estimated date of first subject
enrolled
May 2005
Estimated date of last subject
completed
May 2006

CORDICARE 1 / SINOPE STUDY: Version 07.03.2005

3. Summary

Heart attacks are the leading cause of death in developed countries1. Detection of individuals at increased risk for fatal and non fatal events is therefore of major importance. Preventive measures can reduce the incidence of cardiovascular death and morbidity up to 80%. Guidelines for the treatment of asymptomatic subjects with statins have been recently published 2,3. However, broad epidemiological data are nearly lacking in the Swiss German part of Switzerland, especially with respect to the distribution of cardiovascular risk factors. CORDICARE I is a cross-sectional, population-based screening study to investigate major independent and emerging factors of cardiovascular risk in unselected The first goal will be to investigate the prevalence of the known major risk factors in an unselected population from the Northwest of Switzerland, in the geographical center of the triangle between Basel, Berne, and Zurich, i.e. in Olten. The second goal of the study will be to identify potential candidates for further, more focused studies that compare cardiovascular risk factors with a non-invasive quantification of atherosclerotic lesions by ultrasound-based imaging of the carotid arteries and/or computertomtography-base imaging of coronary calcifications The third goal of CORDICARE I will be to investigate the prevalence of novel cardiovascular risk markers such as elevated high sensitive c-reactive protein (CRP) concentrations in a unselected population in the “Screening In NOrmocholesterolemic Populations for Elevated c-reactive protein” (SINOPE) study. Subjects identified as having elevated high sensitive CRP concentrations will then be invitated to participate in an international study called JUPITER. As part of SINOPE we will in addition ask practitionners in the northwestern part of Switzerland to participate in the search for normocholesterolemic subjects with elevated CRP levels. CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
4. Rationale
Fatal and non fatal cerebral and myocardial infarctions are the leading causes of death and disability in the western world. Moreover, about 50% of these events are not predictable by symptoms but a increased risk might be discovered by rigorous So far, for the Swiss German population in the Northwest of Switzerland, large cross- sectional cohort are not existent and there is in addition a lack of information with respect to the distribution of cardiovascular risk factors in Switzerland among the The determination of classical, well established risk factors such as age, gender, body mass index, systolic and diastolic blood pressure, triglycerides, total, LDL and HDL cholesterol and blood glucose is necessary to investigate any novel risk factors and to determine the added value of these novel and emerging risk factors. During the last decade non-invasive imaging has made enormous progress. For example, computer tomography is now widely used to directly diagnose lung embolism - diagnosis which was for many years very difficult to prove. Novel imaging methods such as the measurement of the carotid intima thickness or coronary calcifications might provide new insights into the development of atherosclerosis and allow for earlier detection of high risk subjects originally thought to have only intermediate or even low coronary risk. Therefore, the accuracy of risk estimations based on the epidemioogical studies can be directly tested and, eventually improved. In addition, very recently high sensitivity C-reactive protein (hsCRP) has become a promising novel marker to predict vascular risk among apparently healthy men and women, even in the absence of hypercholesterolemia. Moreover, it has also been shown that hsCRP can be lowered by the widely used statin therapy4. CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
5. Study Objectives
To determine the prevalence of the known major independent risk factors in an unselected population from the northwestern part of Switzerland To offer this population a cardiovascular risk estimation at no costs for the subjects with the possibility to identify individuals at high or very high risk who can be referred to the general practicionners for further treatment. To identify unselected subjects as potential candidates for further, more focused studies that compare major independent cardiovascular risk factor assessment with the direct non-invasive quantification of atherosclerotic lesions by ultrasound-based imaging of the carotid arteries and/or computertomography- based imaging of coronary calcifications (CORDICARE II-V). To investigate the prevalence of novel cardiovascular risk markers such as elevated hsCRP concentrations in a unselected population in the “Screeening In NOrmocholesterolemic Populations for Elevated c-reactive protein” (SINOPE) To identify subjects (intermediate or low risk) as potential candidates for further, more focused studies that compare the differences regarding cardiovascular events between subjects treated or not treated with statins (worldwide CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
6. Study Organization

6.1 Principal Investigators:
Protective Medicine Foundation Imaging Headquarter, RODIAG Diagnostic Center, Belchenstrasse 18, 4600 Olten Protective Medicine Foundation Laboratory and Gene Headquarter, Kägenstrasse 17, 4153 Reinach Prospective, population-based, single center, cross-sectional study. CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
7. Hypothesis
Based on a recent survey conducted by the Swiss Heart Foundation in Olten in November 2004, we predict many subjects having unidentified major independent cardiovascular risk factors. In that survey conducted in 411 subjects with a mean age of 60 years, 36% of men had an HDL cholesterol < 1.0 mmol/l (9% women), 62% had a systolic blood pressure > 140 mm Hg, and 33% had mild elevantions of glucose (> 6.0 mmol/l). Therefore, we hypothesize, that when screening approximately 5'000 subjects from an unselected random population, we expect to identify approximately 2500 subjects with non-diagnosed or undertreated hypertension, 25-50 subjects with a non-diagnosed, very high risk due to monogenic inherited hypercholesterolemia, 50-100 subjects with an elevated risk due to polygenic hypercholesterolemia, and non-diagnosed 350 diabetic patients and about 700 subjects with the metabolic syndrome. In addition, approximately 10 - 20% or 500 - 1'000 subjects are expected to have elevated hsCRP plasma concentrations. Study Duration and Study Synopsis

Patient recruitement will be started in May 2005 and end, after the inclusion of N =
• Subjects will be invited to the study site in Olten by advertisements in the local newspapers (see text in Appendix 1) • Subjects will be invited to the study site in Olten by an internet website (text in Appendix 2 not yet available). We will also draw the attention of potential participants to the study to our study webaddress (www.infarkt- prävention.ch, www.infarktprävention.ch) that will be advertised in television during three international soccer champions league games, further, general practitionars will be asked to ask subjects for a possible participation in CORDICARE I / SINOPE (see 12.2. for further details). CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
For inclusion in the study subjects must fulfill all of the following criteria: 1. Written informed consent to participate in the study (see Appendix 3) 2. Men aged 45 years and over; women aged 50 years and over Any of the following is regarded as a criterion for exclusion from the study: 1. Subjects not meeting the Inclusion criteria The patients will provide informed written consent before participation in the study and written consent to allow us to contact them for an eventual follow- up study. The consent will be kept in the Investigator on the case report form. Major independent cardiovascular risk factors including blood sample Following enrollment, the subjects will be - interviewed using a questionnaire (see Appendix 4) - clinically examined (age, gender, weight, height, systolic and diastolic blood - blood drawn (cholesterol, blood glucose will be immediately determined by dry chemistry methods (Ascensia Breeze for glucose, Reflotron for cholesterol) to report immediately to the volunteer. Thereafter, blood glucose, total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol will be determined for the study analysis in the Core Study Laboratory. The cardiovascular risk of the volunteer will be estimated from computerized risk assessment algorithm (EU-SCORE Project5). Volunteers at a high risk will be referred to their general practionners. All volunteers will receive a written report with the inclusion of their cardiovascular risk estimation, if appropriate (primary prevention). Volunteers potentially qualifying for further studies (CORDICARE 2-5 and JUPITER) will be planned to be invited for participation in the particular follow-up studies but not before these will be approved by the ethical CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
Institutional Review
The study will be submitted to and approved by an independent ethical committee of Olten, Switzerland, consistent with the revised Declaration of Helsinki. 10. Methodology
10.1. Study Description
Patients who fullfill the inclusion criteria and gave written informed consent for participation in this study will be assessed for total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose, hsCRP. Subjects will have to fill a structured questionnaire (questions about cardiac symptoms, presence of obesity, and assessment of the other cardiovascular risk factors (Appendix 4). A study health nurse will coordinate and organize patients visits and advise study subjects for changes of life stile, if appropriate. In cases, where high risk situation is detected and a referral to a general practionar appears warranted, further counceling and directions are immediately available by the principle 10.2. Description of special investigations
Dry chemistry: For the laboratory tests, a 12 hrs fasting whole-blood sample
(2x7.5ml) will be drawn by a study nurse. First, fasting blood glucose and total cholesterol will be determined by dry chemistry methods (glucose: Ascensia Breeze, Bayer; cholesterol Reflotron, Roche) directly when the volunteer will be still present at the study site and then the interpretation of measurements Blood samples: Second, the whole-blood sample will be sent to the Core
Laboratory of the study (routine laboratories, diagene, Kägenstrasse 17,4153 Reinach). Subsequently, in all study participants, blood glucose and the lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) will be determined by more exact photometric assays. In normocholesterolemic subjects, the relatively expensive high sensitive CRP will be measured in addition. Blood samples will be frozen at –70°C for potential further evaluation (see CORDICARE II-V). Measurement of blood pressure: standardized, upper right or left arm, after
quiet sitting > 3 minutes. Computation of second measurement. CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
11.Safety Issues
Safety reporting is not a real issue in this study, however, because a blood sample will drawn from every volunteer participating in this study, vagal reactions may occur with a albeit small but real risk for complications. Therefore, the study will be insured by a contract covering this risk in every volunteer. 12. Description of the sub studies (not part of the ethical review process)
12.1.The CORDICARE II-V sub studies
1. correlate major independent cardiovascular risk factors with imaging of atherosclerosis and genetic risk factors for cardiovascular diseases (CORDICARE II, N=2000 and III, N=1000), with additional measurements of left ventricular function and laboratory test for heart dysfunction (brain natriuretic peptide, BNP) in 2. perform an outcome study of the originally screened cohort of CORDICARE II 3. selected high participants of CORDICARE II to participate in CORDICARE IV, N=500, where high risk lowering strategies will be made on a usual and intensive See Appendix 6 for a more detailed overview about CORDICARE II-V. 12.2. The SINOPE / JUPITER sub studies (Principal Investigator: André R. Miserez,
In SINOPE (Screening In Normocholesterolemic Populations for Elevated C-reactive protein), the prevalence of subjects with normal or even low LDL cholesterol concentrations and thus, in principle low cardiovascular risk, but elevated high sensi- tive CRP will be determined in an unselected population from the northwestern part of Switzerland. Research from several groups has shown that CRP, a marker of low grade systemic inflammation, is a strong predictor of vascular risk among apparently healthy men and women, even in the absence of hyperlipidemia. Moreover, in studies of over 8000 patients it has been shown that statin therapy lowers CRP in a lipid-independent fashion and that the magnitude of benefit of statin therapy is greater in the presence of high CRP levels. Finally, concerning the critical issue of primary prevention, it has been demonstrated in a hypothesis-generating setting that CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
the absolute risk of a future cardiovascular event among those with low to normal LDL cholesterol levels but above normal CRP levels is just as high as in those with overt hyperlipidemia, and that statin therapy is highly effective in this group. The primary goal will be to collect data about the frequency of subjects with this particular risk profile which is, as high sensitive CRP is not measured usually, difficult to discover. The secondary goal will be to identfy subjects with normal LDL cholesterol (<3.36 mmol/L) but elevated high sensitive CRP levels (>2.0 mg/L) who might participate in the intervention trial (JUPITER). As part of SINOPE we will in addition ask practitionners in the northwestern part of Switzerland to participate in the search for normocholesterolemic subjects with elevated CRP levels. The JUPITER trial is a worldwide ongoing randomized, double-blind, placebo- controlled, multicenter, phase III study of rosuvastatin (Crestor®) 20mg in the primary prevention of cardiovascular events among subjects with low levels of LDL choles- terol and elevated levels of CRP. The primary objective of this study is to investigate whether long-term treatment with rosuvastatin 20mg compared with placebo will de- crease the rate (based on time to first event after randomization) of major cardiovas- cular events (combined endpoint of cardiovascular death, stroke, myocardial infarc- tion, unstable angina, or arterial revascularization) among individuals with low LDL cholesterol (<3.36 mmol/L) who are at high vascular risk on the basis of an enhanced inflammatory response, as determined by elevated levels of CRP (>2.0 mg/L). The secondary objectives of the study are to investigate the safety of long-term treatment with rosuvastatin compared with placebo through comparisons of total mortality, non- cardiovascular mortality, and adverse events, and to investigate whether therapy with rosuvastatin reduces the incidence of diabetes mellitus, venous thromboembolic events, and the incidence of bone fractures. 13. Patient Confidentiality
All information obtained as a result of the study will be regarded as confidential. Clinically relevant results will be transmitted to the referring GP after oral consent has been obtained from the subjects. For data processing, results will be anonimized (initals only plus month/year of birth). Data storage will be done with Dicom. Data will be kept available for health authorities for 10 years in a safe place in the Olten study CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
14. Data Analysis
In this observational prospective cross-sectional study, data are to be collected to ascertain the general health status in a large observational group of subjects. 15. Disclosure of Data and Publication
All information obtained as a result of the study will be regarded as confidential, at least until the appropriate analysis and review by the principal investigators are completed. All rights are reserved to the participating authors. 16. Investigator Approval
We have carefully written and read this protocol and agree that it contains all the necessary information required to conduct the study and we agree to conduct it as described. We understand that this study will not be initiated without formal Ethical Committee approvals and that the administrative requirements of the governing body of the institution will be fully complied with. We have informed and agree that the study will be run according to the Swiss guidelines. Informed written consent will be obtained from all participating subjects and appropriately documented. The undersigned agree that the study will be carried out in conformance with the Declaration of Helsinki (attention beeing drawn to Section 1,9-11, concerning freely given consent). 17. Funding
All examinations performed on patients will be made without charge to the patients or their health insurances. Money will be raised by several means (primarily by private donators, to a lesser extent by the medical industry) and collected in the Protective CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
18. Budget
Inclusion of 5000 randomly selected subjects Screening procedure / Advertisements Newspapers Buro material, post charges, telefone expenditures Health Nurse (EKG, BP, patient history, etc.) Medical investigator (Michel Romanens, MD) Laboratory level 1 (TC, HDLC, TG, Glucose) Medical Work / Statistical analysis / Publication CORDICARE 1 / SINOPE STUDY: Version 07.03.2005

19. Appendices
Appendix 1: Advertisement text (Version 07.03.2005)
Infarkt-Prävention: CORDICARE 1 / SINOPE
Eine kostenlose Untersuchung der Stiftung für Protektive Medizin.
Die Stiftung für Protektive Medizin führt in Olten eine grosse Untersuchung an
voraussichtlich 5000 Personen durch.
In dieser Untersuchung können Sie Ihr Risiko für Herz- und Hirnschlag abschätzen
lassen. Die Untersuchung ist mit einer kurzen Befragung, einer Blutdruckmessung
und einer Blutentnahme verbunden. Ihr Risiko für Herz- und Hirnschlag wird
unmittelbar nach Abschluss der Untersuchungen abgeschätzt und Ihnen in einem
Gespräch erläutert.
Diese Untersuchung ist für Sie kostenlos und dient der Erfassung des Risikos für
Herz- und Hirnschlag in unserer Bevölkerung. Zudem bieten wir Ihnen die
Möglichkeit, an weitergehenden, kostenlosen Untersuchungen teilnehmen zu
können, beispielsweise betreffend der Darstellung Ihrer Blutgefässe anhand von
Messungen des Grades einer allfällig vorhandenen Arterienverkalkung.
Sind Sie interessiert ? Dann vereinbaren Sie einen Termin in Olten über unsere
kostenlose Hotline 0800 xxx. Weitere Informationen finden Sie auch im Internet
(www.infarkt-prävention.ch)
Ihre Stiftung für Protektive Medizin

Appendix 2: website text (not yet available)


CORDICARE 1 / SINOPE STUDY: Version 07.03.2005

Appendix 3: Written informed consent form (Version 07.03.2005)
CORDICARE 1 / SINOPE STUDIEN DER STIF-
TUNG FÜR PROTEKTIVE MEDIZIN
Einverständniserklärung des Probanden und
der Probandin

Ich bin darüber informiert worden, dass diese Studie (CORDICARE I / SINOPE) dazu
dient, mein Risiko für Herz- und Hirninfarkt mit Hilfe von Labormethoden besser
abzuschätzen.
Ich bin damit einverstanden, dass der Hausarzt meiner Wahl im Falle einer weiter
abklärungsbedürftigen Situation informiert werden darf.
Der Name der Hausärztin / des Hausarztes ist _______________________.
Die Praxis befindet sich in folgender Ortschaft: _______________________.
Hiermit bestätige ich mit Datum und meiner Unterschrift, dass ich bereit bin, an
dieser Studie teilzunehmen, mir den Blutdruck messen lasse und mir eine
Blutentnahme machen lasse. Ich kann die Untersuchungen auch jederzeit ohne
weitere Angabe von Gründen abbrechen bzw. unterbrechen.
Datum: _____________________________________________________
Unterschrift: __________________________________________________
Zusätzlich bin ich damit einverstanden, dass mich der Studienleiter Dr. med. Michel
Romanens zu einem späteren Zeitpunkt kontaktieren darf, um mir zukünftige
Studien vorzuschlagen.
Diese zukünftigen Studien beinhalten die Bildgebung der Arterienverkalkung mit
Ultraschall der Halsschlagader und mit Computer-Tomographie der
Herzkranzgefässe, dies in Kombination mit genetischen Risikofaktoren, für
Herzinfarkt und Hirnschlag.
Diese zukünftigen Studien können auch die Prüfung des Effekts neuer Medikamente
auf die Senkung des Risikos für Herzinfarkt und auf die günstige Beeinflussung
neuer Risikofaktoren (hoch sensitives C-reaktives Protein) beinhalten.
Diese Einverständniserklärung ist selbstverständlich für mich nicht bindend und nicht
zwingend. Die heutige Untersuchung kann auch ohne meine Einverständnis, für
weitere Studien in Zukunft kontaktiert werden zu dürfen, durchgeführt werden.
Datum: ____________________________________________________
Unterschrift: __________________________________________________
CORDICARE 1 / SINOPE STUDY: Version 07.03.2005

Appendix 4: Detailed Questionnaire on patients (Version 07.03.2005)

CORDICARE 1 / SINOPE STUDIEN DER
STIFTUNG FÜR PROTEKTIVE MEDIZIN
STUDIEN-FRAGEBOGEN
Probanden-Identifikationsnummer (bitte leer lassen, nicht ausfüllen)
Fragen zu Ihrer Person
Durch Proband auszufüllen
Beispiel
Fragen zu möglichen Herz- und Kreislaufsymptomen
Beim Raschen Gehen Druck oder Klemmen im Bereich des Brustbeins Beim Raschen Gehen Luftmangel, der zum Anhalten zwingt Fragen zu Risikofaktoren und Krankheiten
Ich bin Raucherin / Raucher
Ich habe während xxx Jahren geraucht (Zigaretten, Stumpen, Pfeife) Meine Körpergrösse beträgt (Zentimeter) In der Familie traten Herzinfarkte < 55 bei männlichen und < 65 bei weiblichen Verwandten auf. Ich leide an einer Erkrankung der Herzkranzgefässe Ich habe bereits einmal einen Herzinfarkt erlitten Ich habe bereits einmal eine Streifung oder Hirnschlag erlitten Nehmen Sie Medikamente zur Senkung des Cholesterins ein ? Ich leide an Zuckerkrankheit (Diabetes mellitus) Bitte übergeben Sie dieses Blatt der Studienassistentin. Sie wird mit Ihnendas Blatt durchgehen, den Blutdruck messen und eine Blutentnahme durchführen. Anschliessend wird die Studienassistentin Ihr Risiko fürHerzschlag und Hirnschlag berechnen. Sollten Sie dringend weitere ärztliche Abklärung durch Ihren Hausarzt benötigen, wird Ihnen dies durch die Studienassistentin mitgeteilt. Dies ist zB der Fall bei sehr hohen Blutdruckwerten oder sehr hohenCholesterinwerten. Bei Unklarheiten steht Ihnen im Notfall jederzeit, gegebenenfalls auch nach terminlicher Vereinbarung der Studienleiter, Dr. med. Michel Romanens, zur Verfügung. CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
Appendix 5: German description of the study (Version 07.03.2005)
Die kardiovaskulären Erkrankungen sind in der Schweiz immer noch eine der
häufigsten Ursachen für frühzeitigen Tod und Invalidität. Die von der
internationationalen Atherosklerose-Gesellschaft empfohlene Messung des
kardiovaskulären Risikos anhand von Risikotabellen gestattet bereits eine grobe
Einteilung des Risikos in „hoch, mittel, niedrig“. Leider ereignen sich rund 2/3 der
Herzinfarkte im niedrigen und mittleren Risikobereich. Der mittlere Risikobereich
betrifft gemäss deutschen Erhebungen (PROCAM Studie) rund 15% der
Bevölkerung, welche als Zielgruppe für die verfeinerte Risikoanalyse mit neuen
Methoden identifiziert wurde.
Diese neuen Methoden basieren auf 3 Grundpfeilern: Bildgebung der
Arterienverkalkung (Hals- und Herzschlagadern), Gentests, neue Labortests
(„emerging risk factors“), wie zB hoch sensitives C-reaktives Protein.
Die Stiftung für Protektive Medizin (PMF) hat unter anderem das Ziel, anhand von
populationsbasierten Studien neue epidemiologische Daten in der Deutschschweiz
zu generieren. Zudem können erstmals in grossen Populationen in der Schweiz
etablierte Risikofaktoren mit neuen Risikofaktoren korreliert werden.
Die Studie CORDICARE I / SINOPE ist die erste epidemiologische Studie von PMF.
Anhand von 5000 unselektionierten Personen, welche freiwillig und unentgeltlich
betreffend der konventionellen Risikofaktoren untersucht werden, wird eine
Datenbank geschaffen, welche als Basis für die künftigen Studienprojekte
(CORDICARE II-V). Mit dieser Studie beabsichtigt PMF neben der Generierung
wissenschaftlicher Erkenntnisse im Bereich Epidemiologie kardiovaskulärer
Erkrankungen, auch das Interesse an den Aktivitäten von PMF zu wecken und damit
die Wahrscheinlichkeit für künftige namhafte finanzielle Beiträge für die Projekte
CORIDCARE II-V zu erhöhen.
Mit CORDICARE I / SINOPE möchte PMF auch insbesondere dem Bedürfnis nach
vermehrter Prävention vermeidbarer Krankheiten in der Schweiz entgegen kommen.
Das Studienzenter befindet sich in den Räumlichkeiten des RODIAG Diagnostic
Centers, Belchenstrasse 18, 4600 Olten.
Die Reihenuntersuchungen könnten im Mai 2005 beginnen und werden ca ein Jahr
dauern. Anhand von Inseraten in der Mittelandzeitung und anhand von Internetseiten
(www.infarkt-vorbeugen.ch), auf welche insgesamt drei mal anlässlich von
internationalen Fussball-Länderspielen in der Schweiz anhand von grossen Plakaten
aufmerksam gemacht werden wird, soll das Interesse an CORDICARE I / SINOPE
zusätzlich geweckt werden. Die Teilnehmer werden auf die weiteren
Untersuchungsmöglichkeiten (CORDICARE II-V) aufmerksam gemacht, dürfen
hierfür jedoch nur im späteren Verlauf von PMF kontaktiert werden, wenn eine
schriftliche Einwilligung vorliegt. Interessierte Personen melden sich via Gratis-
Telefonnummer (0800 xxx) an hierfür speziell ausgebildetes Personal im RODIAG
Institut, welches dann einen Termin für die Untersuchung vereinbart. Die
Untersuchung wird von geschultem Personal mit einer Mindest-Ausbildung als
medizinische Praxisassistentin durchgeführt (Personalien, Fragebogen, Blutdruck-
Messung, Blutentnahme, Messung von Cholesterin und Glucose, Berechnung des
globalen Risikos für Herz- und (indirekt) für Hirnschlag anhand des SCORE-
Algorhythmus (http://www.scopri.ch/riskalgorithms.htm). Bei Unklarheiten wendet
sich die Untersucherin an den Studienleiter, Dr. med. Michel Romanens, welche
Fragen der Probanden beantwortet und gegebenenfalls entscheidet, ob ein vom
Proband angegebene(r) Hausärztin oder Hausarzt aufgesucht werden sollte.
CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
Appendix 6: Overview of the CORDICARE studies

The Cordicare Programs
5000 subjectsHx, BP, Chol, HDL, TG, hsCRP 2000 subjects selected from Cordicare IHx, BP, Chol, HDL, TG, hsCRP, atherosclerosis imaging GENE 1000 subjectsHx, BP, CHOL, HDL, TG, hsCRP, atherosclerosis imagingEchocardiography, Aortic Imaging, BNPGENE cohort study over 4 years follow-up with undefined intervals 500 subjects selected from Cordicare IIintensive versus usual primary careGENE, pharmacogenomics, pharmacogenetics cohort study over 4 years of follow up at annual intervals 2000 subjects from Cordicare IIoutcome study: relation of LAB to IMAGING and GENEGENE Hx denotes patient history, BP denotes blood pressure, Chol denotes Cholesterol, HDL denotes HDL
Cholesterol, TG denotes triglycerides, GENE denotes genetic test of cardiovascular risk, LAB denotes
laboratory investigations, IMAGING denotes atherosclerosis imaging non-invasively (ultrasound of
carotid arteries, non-contrast enhanced computed tomography of coronary arteries).



CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
Appendix 7: Calculation of vascular risk
Einleitung:
Die Berechnung des vaskulären Risikos erfolgt anhand eines Risiko-Algorhythmus,
welcher von der EU entwickelt wurde (EU-SCORE, Ref. 5) und das Risiko für die 10-
Jahres Mortalität für Herzinfarkt und nicht kardiale vaskuläre Mortalität berechnet. Da
die vaskuläre Mortalität sich teils aus der Kombination Tod durch Herzschlag und
Tod durch Hirnschlag errechnen lässt (siehe Tabellen unten, separat für Männer und
Frauen und Alterskategorie), kann aus dem EU-SCORE indirekt das Hirnschlag-
Risiko berechnet werden. Der Algorhythmus ist für die Schweiz adaptiert.
Risikokategorien für die gesamte vaskuläre Mortalität (Herzinfarkt und nicht
Herzinfarkt-bedingte vaskuläre Mortalität):
Niedriges Risiko: 0.0-2.9%
Intermediäres Risiko: 3.0-4.9%
Hohes Risiko: 5.0% und mehr
Beispiel:
Mann, 55 jährig, Raucher, Cholesterin 6.5 mmol/l, Blutdruck 144 mm Hg systolisch.
Risikoschätzung für 10 Jahre: (www.scopri.ch/riskalgorithms.htm, inkl Referenz 5 als pdf !)
Herzinfarkt-Sterberisiko:
Nicht Herzinfarkt-bedingte vaskuläre Mortalität: Tödliches Hirnschlag Risiko (11% von 6.7%): Beurteilung des Risikos:
Hohes vaskuläres Mortalitätsrisiko, vor allem bedingt durch das Cholesterin und den
Nikotinabusus. Niedriges Hirnschlagrisiko.
Bemerkung: bei Frauen steigt das relative Risiko für Hirnschlag bei zunehmendem
Alter mehr an als bei den Männern.

Tabelle: Sterbeziffern 1999 nach Diagnose, Schweiz, Bundesamt für Statistik
Sterbefälle und Sterbeziffern wichtiger Todesursachen, nach Alter, Männer
Hirn: Gefässbedingte Erkrankungen des HirnsHerz: Sämtliche Herzkrankheiten Sterbeziffer / 100'000
20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 .85+ Sterbefälle und Sterbeziffern wichtiger Todesursachen, nach Alter, Frauen
Sterbeziffer / 100'000
20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 .85+ TOTAL CORDICARE 1 / SINOPE STUDY: Version 07.03.2005
References

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2 Wood D, De Backer G, Faergeman O, Graham I, Mancia G, Pyörälä K. Prevention of coronary heart disease in clinical practice. Recommendations of the Second Joint Task Force of European and other Societies on coronary prevention. Eur Heart J 1998;19:1434-503. 3 Battegay E, Bertel O, Darioli R, Gutzwiller F, Keller U, Mordasini R, Nigg C, Riesen W.F. Empfehlungen 1999 zur Behandlungsindikation des Risikofaktors Cholesterin. Schweiz Ärztezeitung 1999;80:549-52. 4 The following references are summarized here: 1. Ridker PM. High-sensitivity C-reactive protein: Potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circula-tion 2001;103(13):1813-1818. 2. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among ap-parently healthy women. Circulation 1998;98980:731-733. 3. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflam-mation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336(14):973-979. 4. Ridker PM, Genest J, Libby P. In : Braunwald E, Zipes DP, Liby P, editors. Risk factors for atherosclerotic disease. 6th ed. Philadelphia, PA: WB Saun-ders, Inc.; 2001. p. 1010-1039. 5. Ridker PM, Glynn RJ, Hennekens CH. C-reactive protein adds to the predic-tive value of total and HDL cholesterol in determining risk of first myocardial in-farction. Circulation 1998;97(20):2007-2011. 6. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342(12):836-843. 5 Conroy R, Pyörälä K, Fitzgerald A, et al. Score project group. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J 2003;24:987-1003

Source: http://www.gesundheitscheck.ch/CordicareOne07032005.pdf