title: 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.
abstract: 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'.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  NTR1698 and NTR1106.
authors.affiliation: Erasmus MC, Rotterdam, The Netherlands.|Cardiovascular Research Institute COEUR, Rotterdam, The Netherlands.|Netherlands Heart Institute/Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands.
authors.forename: Rohit M
authors.initials: RM
authors.lastname: Oemrawsingh
authors.affiliation: Erasmus MC, Rotterdam, The Netherlands.|Cardiovascular Research Institute COEUR, Rotterdam, The Netherlands.
authors.forename: K Martijn
authors.initials: KM
authors.lastname: Akkerhuis
authors.affiliation: Medical Center Alkmaar, Alkmaar, The Netherlands.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Umans
authors.affiliation: Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Kietselaer
authors.affiliation: HagaZiekenhuis, The Hague, The Netherlands.
authors.forename: Carl
authors.initials: C
authors.lastname: Schotborgh
authors.affiliation: Reinier de Graaf Hospital, Delft, The Netherlands.
authors.forename: Eelko
authors.initials: E
authors.lastname: Ronner
authors.affiliation: Zuyderland Hospital, Heerlen, The Netherlands.
authors.forename: Timo
authors.initials: T
authors.lastname: Lenderink
authors.affiliation: Sint Franciscus Gasthuis, Rotterdam, The Netherlands.
authors.forename: Anho
authors.initials: A
authors.lastname: Liem
authors.affiliation: Admiraal de Ruyter Hospital, Goes, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Haitsma
authors.affiliation: University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: Division Heart & Lungs, Department of Cardiology, UMC Utrecht, Utrecht, The Netherlands.|Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, The Netherlands.|Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Asselbergs
authors.affiliation: Gelre Hospital, Zutphen, The Netherlands.
authors.forename: Arthur
authors.initials: A
authors.lastname: Maas
authors.affiliation: Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.|Working Group on Cardiovascular Research the Netherlands (WCN), Utrecht, The Netherlands.
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Oude Ophuis
authors.affiliation: Havenziekenhuis, Rotterdam, The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: Ilmer
authors.affiliation: St. Jansdal Hospital, Harderwijk, The Netherlands.
authors.forename: Rene
authors.initials: R
authors.lastname: Dijkgraaf
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Robbert-Jan
authors.initials: RJ
authors.lastname: de Winter
authors.affiliation: Treant Zorggroep, locatie Bethesda, Hoogeveen, The Netherlands.
authors.forename: S Hong Kie
authors.initials: SH
authors.lastname: The
authors.affiliation: Medisch Centrum Haaglanden location Westeinde, Den Haag, The Netherlands.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Wardeh
authors.affiliation: St. Elisabeth Hospital, Tilburg, The Netherlands.
authors.forename: Walter
authors.initials: W
authors.lastname: Hermans
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Etienne
authors.initials: E
authors.lastname: Cramer
authors.affiliation: Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Ron H
authors.initials: RH
authors.lastname: van Schaik
authors.affiliation: Division Heart & Lungs, Department of Cardiology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.affiliation: Netherlands Heart Institute/Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.affiliation: Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Maarten L
authors.initials: ML
authors.lastname: Simoons
authors.affiliation: Erasmus MC, Rotterdam, The Netherlands.|Cardiovascular Research Institute COEUR, Rotterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Boersma
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology; D009206:Myocardium / Q000473:pathology*; D009426:Netherlands; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers
keywords: coronary artery disease; risk stratification; vulnerable period