Download - Biomarcs Study
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BIOMarker study to identify the A cute r isk of a Coronary S yndrome
Eric Boersma
Erasmus MC, Rotterdam, The Netherlands
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Epidemiology of ACS
Annually, in The Netherlands 90,000 subjects are
admitted for an Acute Coronary SyndromeThe annual number of fatal coronary eventsamounts 15,000
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Rotterdam Study
0
1.5
0.5
De Torbal, et al. Eur Heart J 2006;27:729-36
1.0
9060
Recognised MIs per 100 person years
Age (years)
807050
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Euro Heart Survey - Stable Angina
0
6
2
4
123
Death or MI (%)
Follow-up (months)
960
Daly C, et al. BMJ 2006;332:262-267
4.8 events per 100 patient years
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Challenge
How to reduce the incidence of ACS?
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Classical approach
How to reduce the incidence of ACS?
1. Identification of individuals who belong to a groupthat is are at high risk of a coronary event in theperiod (years) ahead
2. Installation of preventive measures , such as life-style changes, medication (e.g. aspirin, statins),revascularisation
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Clinical characteristics and risk
Clinical characteristics are usefull to identify high-risk groups
Most events occur as the result of a sudden,unexpected progression and destabilisation of anonocclusive, asymptomatic coronary lesion
Therefore, clinical baseline characteristics largelyfail to identify episodes of coronary vulnerability in
individual patients
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Challenge
How to reduce the incidence of ACS?
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Alternative approach
How to reduce the incidence of ACS?
1. Identification of vulnerable episodes in the lifetimeof individuals, during which they are at high risk ofan imminent coronary event
2. Timely installation of (intensified) preventivetherapy
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The role of (non)invasive imaging
Several imaging techniques are available toanalyse plaque composition and indicate its
stability level (e.g. IVUS, MS-CT, MRI)However, atherosclerosis is a dynamic process -lesions that are stable today, might be destabilised
tomorrowLong-term and permanent risk-monitoring byinvasive imaging techniques is infeasible
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Hypothesis
Inflammation plays a central role in coronaryplaque progression resulting in an ACS
Vascular inflammation becomes activated severaldays or weeks before the coronary event
Biomarkers of inflammation and hypercoagulabilitywill be elevated before the event
Hence, serial biomarker measurements might be
used to identify vulnerable episodes in the lifetimeof individuals, during which they are at high risk ofan imminent ACS
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Biomarkers during follow-up
1 2 3 4 5 6
Biomarker pattern associatedwith a stable coronary period
Regular blood samplesduring follow-up
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Biomarkers during follow-up
Vulnerable episode
1 2 3 4 5 6Regular blood samples
during follow-up
Biomarker pattern associatedwith a high risk of an ACSevent in the vulnerableepisode between samples 4-6
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Research Program - Perspective
The long-term perspective of the ResearchProgram is to develop treatment strategies, based
on frequent biomarker evaluation, to preventcoronary events that are about to occur
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Research Program - Short-term goal
The short-term goal (5 year horizon) of theResearch Program is to unravel the relation
between biomarkers patterns and the incidence ofcoronary events during prolonged follow-up in(post)ACS patients
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Research Program
1. Selection of candidate biomarkers - Literature2. Variability in biomarker patterns after admission
for ACS - BIOMArCS-pilot3. Biomarker patterns and coronary events during
long-term follow-up in ACS patients - BIOMArCS4. Development of a dynamic risk model to
recognise episodes of coronary vulnerability in(post)ACS patients, combining serial clinical andbiomarker data
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Time schedule
2008 2009 2010 2011 2012
Project 1
Project 2A
Project 2B
Project 3
Project 4
PhD
PhD
PhD
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Project 3 - BIOMArCS
Relation between biomarker patterns duringfollow-up and incident coronary events in ACSpatientsPatients admitted for ACS
2 risk factors
N=70021 sampling moments
admission, discharge, each 14 days until 6 months,then each month until 1 year
Analysis: 70 cases (i.e. patients with repeat ACS;10%) + 210 controls * 15 samples (on average)
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Project 3 - BIOMArCS
Sponsorship: Dutch Heart Foundation, ICIN,Erasmus MC
Academic hospitals (ICIN)Rotterdam, Maastricht, Utrecht, Amsterdam (AMC),Groningen
Non-academic hospitals (WCN) Alkmaar, Den Haag (MCH Westeinde), Goes,Harderwijk, Heerlen, Nijmegen, Rotterdam (MCRZand Havenziekenhuis), Zoetermeer
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What is our request?
Active participation in a nationwide jointcollaboration between ICIN and WCN.
Inclusion of 50 patients within 1.5 yearsInvestment in infrastructure
Efforts to carefully complete the protocol for eachpatient(strictly observational and nurse driven study)
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Contact Details
Eric Boersma, principal investigator [email protected]
Martijn Akkerhuis, cardiologist
Rohit Oemrawsingh, PhD [email protected]