BIOMarker study to identify the Acute risk of a Coronary Syndrome

Eric Boersma Erasmus MC, Rotterdam, The Netherlands

Epidemiology of ACS
Annually, in The Netherlands 90,000 subjects are admitted for an Acute Coronary Syndrome The annual number of fatal coronary events amounts 15,000

Rotterdam Study
Recognised MIs per 100 person years 1.5

1.0

0.5

0 50 60 70 Age (years)
De Torbal, et al. Eur Heart J 2006;27:729-36

80

90

Euro Heart Survey - Stable Angina

Death or MI (%) 6 4.8 events per 100 patient years 4

0 0
Daly C, et al. BMJ 2006;332:262-267

6 Follow-up (months)

12

Challenge
How to reduce the incidence of ACS?

Classical approach
How to reduce the incidence of ACS? 1. Identification of individuals who belong to a group that is are at high risk of a coronary event in the period (years) ahead 2. Installation of preventive measures, such as lifestyle changes, medication (e.g. aspirin, statins), revascularisation

Clinical characteristics and risk

Clinical characteristics are usefull to identify highrisk groups Most events occur as the result of a sudden, unexpected progression and destabilisation of a nonocclusive, asymptomatic coronary lesion Therefore, clinical baseline characteristics largely fail to identify episodes of coronary vulnerability in individual patients

Challenge
How to reduce the incidence of ACS?

Alternative approach
How to reduce the incidence of ACS? 1. Identification of vulnerable episodes in the lifetime of individuals, during which they are at high risk of an imminent coronary event 2. Timely installation of (intensified) preventive therapy

The role of (non)invasive imaging

Several imaging techniques are available to analyse 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 tomorrow Long-term and permanent risk-monitoring by invasive imaging techniques is infeasible

Hypothesis
Inflammation plays a central role in coronary plaque progression resulting in an ACS Vascular inflammation becomes activated several days or weeks before the coronary event Biomarkers of inflammation and hypercoagulability will be elevated before the event Hence, serial biomarker measurements might be used to identify vulnerable episodes in the lifetime of individuals, during which they are at high risk of an imminent ACS

Biomarkers during follow-up

Biomarker pattern associated with a stable coronary period

Regular blood samples during follow-up

Biomarkers during follow-up

Vulnerable episode

Biomarker pattern associated with a high risk of an ACS event in the vulnerable episode between samples 4-6

Regular blood samples during follow-up

Research Program - Perspective

The long-term perspective of the Research Program is to develop treatment strategies, based on frequent biomarker evaluation, to prevent coronary events that are about to occur

Research Program - Short-term goal

The short-term goal (5 year horizon) of the Research Program is to unravel the relation between biomarkers patterns and the incidence of coronary events during prolonged follow-up in (post)ACS patients

Research Program
1. Selection of candidate biomarkers - Literature 2. Variability in biomarker patterns after admission for ACS - BIOMArCS-pilot 3. Biomarker patterns and coronary events during long-term follow-up in ACS patients - BIOMArCS 4. Development of a dynamic risk model to recognise episodes of coronary vulnerability in (post)ACS patients, combining serial clinical and biomarker data

Time schedule
Project 1 Project 2A PhD Project 2B Project 3 Project 4 2008 2009 2010 2011 2012 PhD PhD

Project 3 - BIOMArCS
Relation between biomarker patterns during follow-up and incident coronary events in ACS patients Patients admitted for ACS
2 risk factors

N=700 21 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)

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 (MCRZ and Havenziekenhuis), Zoetermeer

What is our request?

Active participation in a nationwide joint collaboration between ICIN and WCN. Inclusion of 50 patients within 1.5 years
Investment in infrastructure

Efforts to carefully complete the protocol for each patient (strictly observational and nurse driven study)

What do we offer?
An innovative project under ICIN-WCN umbrella Hospitals: Participation in an innovative, nationwide study
Co-authorship Additional analyses (if adequately funded)

Cost-effective data-collection fee per patient Material (tubes + scanner) for free Electronic & www-based CRF Patient travel costs 10 for each non-regular visit

Contact Details
Eric Boersma, principal investigator h.boersma@erasmusmc.nl Martijn Akkerhuis, cardiologist k.akkerhuis@erasmusmc.nl Rohit Oemrawsingh, PhD fellow r.oemrawsingh@erasmusmc.nl