biomarcs study

8/12/2019 Biomarcs Study

1/22

BIOMarker study to identify the A cute r isk of a Coronary S yndrome

Eric Boersma

Erasmus MC, Rotterdam, The Netherlands


2/22

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


3/22

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


4/22

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


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



9/22

Alternative approach


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


16/22

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)


19/22

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


20/22

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)


21/22


22/22

Contact Details

Eric Boersma, principal investigator [email protected]

Martijn Akkerhuis, cardiologist

[email protected]

Rohit Oemrawsingh, PhD [email protected]

biomarcs study

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