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Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome—a prospective multicentre biomarker study conducted in the Netherlands
  1. Rohit M Oemrawsingh1,2,3,
  2. K Martijn Akkerhuis1,2,
  3. Victor A Umans4,
  4. Bas Kietselaer5,
  5. Carl Schotborgh6,
  6. Eelko Ronner7,
  7. Timo Lenderink8,
  8. Anho Liem9,
  9. David Haitsma10,
  10. Pim van der Harst11,
  11. Folkert W Asselbergs12,13,14,
  12. Arthur Maas15,
  13. Anton J Oude Ophuis16,17,
  14. Ben Ilmer18,
  15. Rene Dijkgraaf19,
  16. Robbert-Jan de Winter20,
  17. S Hong Kie The21,
  18. Alexander J Wardeh22,
  19. Walter Hermans23,
  20. Etienne Cramer24,
  21. Ron H van Schaik1,
  22. Imo E Hoefer12,
  23. Pieter A Doevendans3,
  24. Maarten L Simoons1,
  25. Eric Boersma1,2
  1. 1Erasmus MC, Rotterdam, The Netherlands
  2. 2Cardiovascular Research Institute COEUR, Rotterdam, The Netherlands
  3. 3Netherlands Heart Institute/Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands
  4. 4Medical Center Alkmaar, Alkmaar, The Netherlands
  5. 5Maastricht University Medical Center, Maastricht, The Netherlands
  6. 6HagaZiekenhuis, The Hague, The Netherlands
  7. 7Reinier de Graaf Hospital, Delft, The Netherlands
  8. 8Zuyderland Hospital, Heerlen, The Netherlands
  9. 9Sint Franciscus Gasthuis, Rotterdam, The Netherlands
  10. 10Admiraal de Ruyter Hospital, Goes, The Netherlands
  11. 11University of Groningen, University Medical Center Groningen, The Netherlands
  12. 12Division Heart & Lungs, Department of Cardiology, UMC Utrecht, Utrecht, The Netherlands
  13. 13Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, The Netherlands
  14. 14Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London, UK
  15. 15Gelre Hospital, Zutphen, The Netherlands
  16. 16Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands
  17. 17Working Group on Cardiovascular Research the Netherlands (WCN), Utrecht, The Netherlands
  18. 18Havenziekenhuis, Rotterdam, The Netherlands
  19. 19St. Jansdal Hospital, Harderwijk, The Netherlands
  20. 20Academic Medical Center, Amsterdam, The Netherlands
  21. 21Treant Zorggroep, locatie Bethesda, Hoogeveen, The Netherlands
  22. 22Medisch Centrum Haaglanden location Westeinde, Den Haag, The Netherlands
  23. 23St. Elisabeth Hospital, Tilburg, The Netherlands
  24. 24Radboud University Medical Center, Nijmegen, The Netherlands
  1. Correspondence to Professor Eric Boersma; h.boersma{at}


Purpose Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such ‘vulnerable periods’.

Participants BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor.

Methods and analysis We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate ‘vulnerable periods’ during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case–cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS.

Future plans and dissemination Follow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should identification of a ‘vulnerable period’ prove to be feasible, then future research could focus on event reduction through pharmacological or mechanical intervention during such periods of high risk for ACS.

Trial registration number NTR1698 and NTR1106.

  • coronary artery disease
  • risk stratification
  • vulnerable period

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  • Contributors RMO, KMA, EB and MLS were responsible for the design of the BIOMArCS study. RMO drafted the manuscript. All other authors, KMA, EB, MLS, VAU, BK, CS, ER, TL, AL, DH, PvdH, FWA, AM, AJOO, BI, RD, R-JdW, SHKT, AJW, WH, EC, RHvS, IEH, PAD, revised it critically for important intellectual content and approved this version to be published. All authors contributed substantially to data acquisition for the BIOMArCS study and agree to be accountable for all aspects of this work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding The study is supported and funded by the Netherlands Heart Foundation (grant number 2007B012), the Netherlands Heart Institute-Interuniversity Cardiology Institute of the Netherlands (project number 071.01) and the Working Group on Cardiovascular Research Netherlands, all of which are non-commercial funding bodies. An unrestricted research grant is further obtained from Eli Lilly, the Netherlands. FWA is supported by a Dekker scholarship-Junior Staff Member 2014T001—the Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre.

  • Competing interests BIOMArCS was designed and initiated by the principal investigators. The trial will be conducted, and its results interpreted and reported independently of the aforementioned sponsors.

  • Ethics approval IRB of the ErasmusMC for national approval and subsequently the IRB of every participating institution for local approval.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Anyone can submit a prespecified analytical plan for biomarker analyses within the BIOMArCS data set to the principal investigator/Clinical Epidemiology Unit of the Erasmus MC Department of Cardiology. Biomarker analyses can only be performed after evaluation and written approval thereof by the BIOMArCS Executive Committee.

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