{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:39:09Z","timestamp":1787017149851,"version":"build-2736575974"},"reference-count":51,"publisher":"BMJ","issue":"12","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2016,10,13]]},"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>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 \u2018vulnerable periods\u2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>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 \u2018vulnerable periods\u2019 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\u2013cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Future plans and dissemination<\/jats:title>\n                    <jats:p>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 \u2018vulnerable period\u2019 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NTR1698 and NTR1106.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2016-012929","type":"journal-article","created":{"date-parts":[[2016,12,24]],"date-time":"2016-12-24T14:35:07Z","timestamp":1482590107000},"page":"e012929","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome\u2014a prospective multicentre biomarker study conducted in the Netherlands"],"prefix":"10.1136","volume":"6","author":[{"given":"Rohit M","family":"Oemrawsingh","sequence":"first","affiliation":[{"name":"Erasmus MC, Rotterdam, The Netherlands"},{"name":"Cardiovascular Research Institute COEUR, Rotterdam, The Netherlands"},{"name":"Netherlands Heart Institute\/Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K Martijn","family":"Akkerhuis","sequence":"additional","affiliation":[{"name":"Erasmus MC, Rotterdam, The Netherlands"},{"name":"Cardiovascular Research Institute COEUR, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor A","family":"Umans","sequence":"additional","affiliation":[{"name":"Medical Center Alkmaar, Alkmaar, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas","family":"Kietselaer","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Schotborgh","sequence":"additional","affiliation":[{"name":"HagaZiekenhuis, The Hague, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eelko","family":"Ronner","sequence":"additional","affiliation":[{"name":"Reinier de Graaf Hospital, Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Lenderink","sequence":"additional","affiliation":[{"name":"Zuyderland Hospital, Heerlen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anho","family":"Liem","sequence":"additional","affiliation":[{"name":"Sint Franciscus Gasthuis, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Haitsma","sequence":"additional","affiliation":[{"name":"Admiraal de Ruyter Hospital, Goes, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pim","family":"van der Harst","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert W","family":"Asselbergs","sequence":"additional","affiliation":[{"name":"Division Heart & Lungs, Department of Cardiology, UMC Utrecht, Utrecht, The Netherlands"},{"name":"Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, The Netherlands"},{"name":"Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Maas","sequence":"additional","affiliation":[{"name":"Gelre Hospital, Zutphen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton J","family":"Oude Ophuis","sequence":"additional","affiliation":[{"name":"Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands"},{"name":"Working Group on Cardiovascular Research the Netherlands (WCN), Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Ilmer","sequence":"additional","affiliation":[{"name":"Havenziekenhuis, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Dijkgraaf","sequence":"additional","affiliation":[{"name":"St. Jansdal Hospital, Harderwijk, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbert-Jan","family":"de Winter","sequence":"additional","affiliation":[{"name":"Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S Hong Kie","family":"The","sequence":"additional","affiliation":[{"name":"Treant Zorggroep, locatie Bethesda, Hoogeveen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"Wardeh","sequence":"additional","affiliation":[{"name":"Medisch Centrum Haaglanden location Westeinde, Den Haag, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Hermans","sequence":"additional","affiliation":[{"name":"St. Elisabeth Hospital, Tilburg, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Cramer","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron H","family":"van Schaik","sequence":"additional","affiliation":[{"name":"Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imo E","family":"Hoefer","sequence":"additional","affiliation":[{"name":"Division Heart & Lungs, Department of Cardiology, UMC Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter A","family":"Doevendans","sequence":"additional","affiliation":[{"name":"Netherlands Heart Institute\/Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten L","family":"Simoons","sequence":"additional","affiliation":[{"name":"Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Boersma","sequence":"additional","affiliation":[{"name":"Erasmus MC, Rotterdam, The Netherlands"},{"name":"Cardiovascular Research Institute COEUR, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2016,12,23]]},"reference":[{"key":"2025121403214832000_6.12.e012929.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(05)80050-X"},{"key":"2025121403214832000_6.12.e012929.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0195-668X(03)00114-3"},{"key":"2025121403214832000_6.12.e012929.3","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.22.2557"},{"key":"2025121403214832000_6.12.e012929.4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.284.7.835"},{"key":"2025121403214832000_6.12.e012929.5","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-004425"},{"key":"2025121403214832000_6.12.e012929.6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.7.898"},{"key":"2025121403214832000_6.12.e012929.7","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.08.1056"},{"key":"2025121403214832000_6.12.e012929.8","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000087481.55887.C9"},{"key":"2025121403214832000_6.12.e012929.9","doi-asserted-by":"publisher","DOI":"10.1136\/heart.83.3.361"},{"key":"2025121403214832000_6.12.e012929.10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.305637"},{"key":"2025121403214832000_6.12.e012929.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(06)02029-7"},{"key":"2025121403214832000_6.12.e012929.12","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1586\/14779072.6.4.435","article-title":"Tailor-made therapy for the prevention of acute coronary syndromes: future role of biomarkers in risk stratification and disease management","volume":"6","author":"Oemrawsingh","year":"2008","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"2025121403214832000_6.12.e012929.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2014.08.013"},{"key":"2025121403214832000_6.12.e012929.14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.atherosclerosis.2016.02.012","article-title":"High-sensitivity troponin T in relation to coronary plaque characteristics in patients with stable coronary artery disease; results of the ATHEROREMO-IVUS study","volume":"247","author":"Oemrawsingh","year":"2016","journal-title":"Atherosclerosis"},{"key":"2025121403214832000_6.12.e012929.15","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3109\/1354750X.2014.957725","article-title":"Circulating chemokines in relation to coronary plaque characteristics on radiofrequency intravascular ultrasound and cardiovascular outcome","volume":"19","author":"Cheng","year":"2014","journal-title":"Biomarkers"},{"key":"2025121403214832000_6.12.e012929.16","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.ijcard.2014.11.001","article-title":"Circulating acute phase proteins in relation to extent and composition of coronary atherosclerosis and cardiovascular outcome: results from the ATHEROREMO-IVUS study","volume":"177","author":"Battes","year":"2014","journal-title":"Int J Cardiol"},{"key":"2025121403214832000_6.12.e012929.17","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.atherosclerosis.2015.10.022","article-title":"Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome: results of the ATHEROREMO-IVUS study","volume":"243","author":"Cheng","year":"2015","journal-title":"Atherosclerosis"},{"key":"2025121403214832000_6.12.e012929.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.06.010"},{"key":"2025121403214832000_6.12.e012929.19","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1160\/TH14-07-0589","article-title":"Von Willebrand factor in relation to coronary plaque characteristics and cardiovascular outcome. Results of the ATHEROREMO-IVUS study","volume":"113","author":"Sonneveld","year":"2015","journal-title":"Thromb Haemost"},{"key":"2025121403214832000_6.12.e012929.20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.atherosclerosis.2016.03.010","article-title":"PCSK9 in relation to coronary plaque inflammation: results of the ATHEROREMO-IVUS study","volume":"248","author":"Cheng","year":"2016","journal-title":"Atherosclerosis"},{"key":"2025121403214832000_6.12.e012929.21","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043814"},{"key":"2025121403214832000_6.12.e012929.22","unstructured":"Grobbee DE , Hoes AW . Clinical epidemiology: principles, methods, and applications for clinical research. Boston: Jones and Bartlett Publishers, 2009:259\u201361."},{"key":"2025121403214832000_6.12.e012929.23","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1002\/clc.21988","article-title":"Lipoprotein(a), interleukin-10, C-reactive protein, and 8-year outcome after percutaneous coronary intervention","volume":"35","author":"Kardys","year":"2012","journal-title":"Clin Cardiol"},{"key":"2025121403214832000_6.12.e012929.24","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2010.197392"},{"key":"2025121403214832000_6.12.e012929.25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1415921"},{"key":"2025121403214832000_6.12.e012929.26","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1515\/cclm-2012-0786","article-title":"High-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide predict mortality in stable coronary artery disease: results from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study","volume":"51","author":"Giannitsis","year":"2013","journal-title":"Clin Chem Lab Med"},{"key":"2025121403214832000_6.12.e012929.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.04.027"},{"key":"2025121403214832000_6.12.e012929.28","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304964"},{"key":"2025121403214832000_6.12.e012929.29","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2013.209858"},{"key":"2025121403214832000_6.12.e012929.30","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv236"},{"key":"2025121403214832000_6.12.e012929.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ehj.2004.06.009"},{"key":"2025121403214832000_6.12.e012929.32","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn075"},{"key":"2025121403214832000_6.12.e012929.33","doi-asserted-by":"crossref","unstructured":"Verbeke G , Molenberghs G . Linear mixed models for longitudinal data. New York: Springer-Verlag, 2000.","DOI":"10.1007\/978-1-4419-0300-6"},{"key":"2025121403214832000_6.12.e012929.34","doi-asserted-by":"crossref","unstructured":"Rizopoulos R . Joint models for longitudinal and time-to-event data with applications in R. London: Chapman and Hall\/CRC, 2012.","DOI":"10.1201\/b12208"},{"key":"2025121403214832000_6.12.e012929.35","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwr374"},{"key":"2025121403214832000_6.12.e012929.36","unstructured":"Coordinating Center for the Global Registry of Acute Coronary Events, Center for Outcomes Research, University of Massachusetts Medical School. Methods and formulas used to calculate the GRACE Risk Scores for patients presenting to hospital with an acute coronary syndrome. https:\/\/www.outcomes-umassmed.org\/grace\/files\/GRACE_RiskModel_Coefficients.pdf (accessed 3 May 2016)."},{"key":"2025121403214832000_6.12.e012929.37","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.4244\/EIJV9I12A245","article-title":"Tools and techniques\u2014statistics: how many variables are allowed in the logistic and Cox regression models?","volume":"9","author":"van Domburg","year":"2014","journal-title":"EuroIntervention"},{"key":"2025121403214832000_6.12.e012929.38","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht484"},{"key":"2025121403214832000_6.12.e012929.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.07.998"},{"key":"2025121403214832000_6.12.e012929.40","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2004.038364"},{"key":"2025121403214832000_6.12.e012929.41","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000157141.00778.AC"},{"key":"2025121403214832000_6.12.e012929.42","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.2002.3159"},{"key":"2025121403214832000_6.12.e012929.43","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.607333"},{"key":"2025121403214832000_6.12.e012929.44","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.9.903"},{"key":"2025121403214832000_6.12.e012929.45","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.17.2063"},{"key":"2025121403214832000_6.12.e012929.46","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.17.2292"},{"key":"2025121403214832000_6.12.e012929.47","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.016080"},{"key":"2025121403214832000_6.12.e012929.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.03.003"},{"key":"2025121403214832000_6.12.e012929.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.10.027"},{"key":"2025121403214832000_6.12.e012929.50","first-page":"174","article-title":"Closing the loop on inflammation and atherothrombosis: why perform the CIRT and CANTOS trials?","volume":"124","author":"Ridker","year":"2013","journal-title":"Trans Am Clin Climatol Assoc"},{"key":"2025121403214832000_6.12.e012929.51","doi-asserted-by":"crossref","unstructured":"Fuster V , Sanz J . Gene therapy and stem cell therapy for cardiovascular diseases today: a model for translational research. Nat Clin Pract Cardiovasc Med 2007;(4 Suppl 1):S1\u20138 doi:10.1038\/ncpcardio0737.","DOI":"10.1038\/ncpcardio0737"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2016-012929","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T11:21:53Z","timestamp":1765711313000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2016-012929"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12,23]]},"published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1136\/bmjopen-2016-012929"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2016-012929","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12]]}}}