{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:34:36Z","timestamp":1790818476322,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"MORGAM","award":["BMH4-CT98-3183"],"award-info":[{"award-number":["BMH4-CT98-3183"]}]},{"name":"GenomEUtwin","award":["QLG2-CT-2002-01254"],"award-info":[{"award-number":["QLG2-CT-2002-01254"]}]},{"name":"ENGAGE","award":["HEALTH-F4-2007-201413"],"award-info":[{"award-number":["HEALTH-F4-2007-201413"]}]},{"name":"CHANCES","award":["HEALTH-F3-2010-242244"],"award-info":[{"award-number":["HEALTH-F3-2010-242244"]}]},{"name":"BiomarCaRE","award":["HEALTH-F2-2011-278913"],"award-info":[{"award-number":["HEALTH-F2-2011-278913"]}]},{"name":"euCanSHare","award":["825903"],"award-info":[{"award-number":["825903"]}]},{"name":"euCanSHare","award":["847770"],"award-info":[{"award-number":["847770"]}]},{"name":"AFFECT-EU","award":["847770"],"award-info":[{"award-number":["847770"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0601463"],"award-info":[{"award-number":["G0601463"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["80983"],"award-info":[{"award-number":["80983"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Community Medicine Research Network of the University Medicine Greifswald"},{"name":"German Federal State of Mecklenburg"},{"name":"Health Administration of the Lombardia Region","award":["17155\/2004"],"award-info":[{"award-number":["17155\/2004"]}]},{"name":"Health Administration of the Lombardia Region","award":["10800\/2009"],"award-info":[{"award-number":["10800\/2009"]}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["2012\/597"],"award-info":[{"award-number":["2012\/597"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013295","name":"Helmholtz Zentrum M\u00fcnchen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013295","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Research Center for Environmental Health"},{"name":"German Federal Ministry of Education and Research"},{"name":"State of Bavaria"},{"name":"University Hospital of Augsburg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We used individual-level data of 95 292 individuals of the European population harmonized in the Biomarker for Cardiovascular Risk Assessment across Europe consortium and investigated the prognostic ability of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). Cox-regression models were used to determine adjusted hazard ratios of diabetes and log-transformed biomarkers for fatal and non-fatal cardiovascular events. Models were compared using the likelihood ratio test. Stratification by specific biomarker cut-offs was performed for crude time-to-event analysis using Kaplan\u2013Meier plots. Overall, 6090 (6.4%) individuals had diabetes at baseline, median follow-up was 9.9 years. Adjusting for classical risk factors and biomarkers, diabetes [HR 2.11 (95% CI 1.92, 2.32)], and all biomarkers (HR per interquartile range hs-cTnI 1.08 [95% CI 1.04, 1.12]; NT-proBNP 1.44 [95% CI 1.37, 1.53]; hs-CRP 1.27 [95% CI 1.21, 1.33]) were independently associated with cardiovascular events. Specific cut-offs for each biomarker identified a high-risk group of individuals with diabetes losing a median of 15.5 years of life compared to diabetics without elevated biomarkers. Addition of biomarkers to the Cox-model significantly improved the prediction of outcomes (likelihood ratio test for nested models P &amp;lt; 0.001), accompanied by an increase in the c-index (increase to 0.81).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Biomarkers improve cardiovascular risk prediction in individuals with and without diabetes and facilitate the identification of individuals with diabetes at highest risk for cardiovascular events.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwad122","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T17:25:14Z","timestamp":1682011514000},"page":"1218-1226","source":"Crossref","is-referenced-by-count":14,"title":["Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals with diabetes mellitus"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7714-4446","authenticated-orcid":false,"given":"Paul M","family":"Haller","sequence":"first","affiliation":[{"name":"Department for Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf , Martinistrasse 52, 20246 Hamburg , Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/Luebeck , Martinistrasse 52, 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5211-5593","authenticated-orcid":false,"given":"Alina","family":"Go\u00dfling","sequence":"additional","affiliation":[{"name":"Department for Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf , Martinistrasse 52, 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5102-0955","authenticated-orcid":false,"given":"Christina","family":"Magnussen","sequence":"additional","affiliation":[{"name":"Department for Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf , Martinistrasse 52, 20246 Hamburg , Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/Luebeck , Martinistrasse 52, 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[{"name":"German Cancer Research Center, Division of Clinical Epidemiology and Aging Research , Im Neuenheimer Feld 280, 69120 Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-4521","authenticated-orcid":false,"given":"Ben","family":"Sch\u00f6ttker","sequence":"additional","affiliation":[{"name":"German Cancer Research Center, Division of Clinical Epidemiology and Aging Research , Im Neuenheimer Feld 280, 69120 Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0514-5885","authenticated-orcid":false,"given":"Licia","family":"Iacoviello","sequence":"additional","affiliation":[{"name":"1) Department of Epidemiology and Prevention, IRCCS NEUROMED , Via Atinense, 18, 86077 Pozzilli , Italy"},{"name":"Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria , Via O. Rossi 9, 21100 Varese , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4569-1186","authenticated-orcid":false,"given":"Simona","family":"Costanzo","sequence":"additional","affiliation":[{"name":"1) Department of Epidemiology and Prevention, IRCCS NEUROMED , Via Atinense, 18, 86077 Pozzilli , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Kee","sequence":"additional","affiliation":[{"name":"Centre for Public Health, Queens University of Belfast , Belfast BT12 6BA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2064-9603","authenticated-orcid":false,"given":"Wolfgang","family":"Koenig","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Herz-& Kreislauferkrankungen, Deutsches Herzzentrum M\u00fcnchen, Technische Universit\u00e4t M\u00fcnchen , Lazarettstra\u00dfe 36, 80636 M\u00fcnchen , Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance , Lazarettstra\u00dfe 36, 80636 Munich , Germany"},{"name":"Institute of Epidemiology and Medical Biometry, University of Ulm , Helmholtzstr. 22, 89081 Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0994-0184","authenticated-orcid":false,"given":"Allan","family":"Linneberg","sequence":"additional","affiliation":[{"name":"Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region of Denmark , Ndr. Fasanvej 57, 1. sal, Bygning 14, 2000 Frederiksber , Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, 2200 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaterina","family":"Sujana","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Helmholtz Zentrum M\u00fcnchen - German Research Center for Environmental Health, Institute of Epidemiology , Ingolst\u00e4dter Landstra\u00dfe 1, 85764 Neuherberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5667-6849","authenticated-orcid":false,"given":"Barbara","family":"Thorand","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Helmholtz Zentrum M\u00fcnchen - German Research Center for Environmental Health, Institute of Epidemiology , Ingolst\u00e4dter Landstra\u00dfe 1, 85764 Neuherberg , Germany"},{"name":"German Center for Diabetes Research (DZD) , Ingolst\u00e4dter Landstra\u00dfe 1, 85764 Neuherberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-5324","authenticated-orcid":false,"given":"Veikko","family":"Salomaa","sequence":"additional","affiliation":[{"name":"Finnish Institute for Health and Welfare, Department of Public Health and Welfare , P.O. Box 30, FI-00271 Helsinki , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teemu J","family":"Niiranen","sequence":"additional","affiliation":[{"name":"Finnish Institute for Health and Welfare, Department of Public Health and Welfare , P.O. Box 30, FI-00271 Helsinki , Finland"},{"name":"Department of Medicine, Turku University Hospital and University of Turku , Kiinamyllynkatu 10, 20520 Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"S\u00f6derberg","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine, Ume\u00e5 University , 901 87 Ume\u00e5 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"V\u00f6lzke","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Community Medicine, Funktionsbereich SHIP\/KEF, University Medicine Greifswald , Walter Rathenau Str. 48, 17475 Greifswald , Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Greifswald , Walter Rathenau Str. 48, 17475 Greifswald , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7471-475X","authenticated-orcid":false,"given":"Marcus","family":"D\u00f6rr","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Greifswald , Walter Rathenau Str. 48, 17475 Greifswald , Germany"},{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin B, University Medicine Greifswald , Ferdinand-Sauerbruch-Stra\u00dfe, 17475 Greifswald , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0400-5197","authenticated-orcid":false,"given":"Susana","family":"Sans","sequence":"additional","affiliation":[{"name":"Catalan Department of Health , Roc Boronat, 81, 08005 Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Padr\u00f3","sequence":"additional","affiliation":[{"name":"Cardiovascular-Program ICCC, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU) , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan B","family":"Felix","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Greifswald , Walter Rathenau Str. 48, 17475 Greifswald , Germany"},{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin B, University Medicine Greifswald , Ferdinand-Sauerbruch-Stra\u00dfe, 17475 Greifswald , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Nauck","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Greifswald , Walter Rathenau Str. 48, 17475 Greifswald , Germany"},{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald , Ferdinand-Sauerbruch-Stra\u00dfe, 17489 Greifswald , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Petersmann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald , Ferdinand-Sauerbruch-Stra\u00dfe, 17489 Greifswald , Germany"},{"name":"University Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Oldenburg , Rahel-Straus-Stra\u00dfe 10, 26133 Oldenburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Endocrine-metabolic Diseases and Aging, Istituto Superiore di Sanit\u00e0-ISS , 299 Viale Regina Elena, 00161 Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8040-5571","authenticated-orcid":false,"given":"Chiara","family":"Donfrancesco","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Endocrine-metabolic Diseases and Aging, Istituto Superiore di Sanit\u00e0-ISS , 299 Viale Regina Elena, 00161 Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"De Ponti","sequence":"additional","affiliation":[{"name":"Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria , Via O. Rossi 9, 21100 Varese , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4119-6615","authenticated-orcid":false,"given":"Giovanni","family":"Veronesi","sequence":"additional","affiliation":[{"name":"Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria , Via O. Rossi 9, 21100 Varese , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco M","family":"Ferrario","sequence":"additional","affiliation":[{"name":"Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria , Via O. Rossi 9, 21100 Varese , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2165-1411","authenticated-orcid":false,"given":"Kari","family":"Kuulasmaa","sequence":"additional","affiliation":[{"name":"Finnish Institute for Health and Welfare, Department of Public Health and Welfare , P.O. Box 30, FI-00271 Helsinki , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Zeller","sequence":"additional","affiliation":[{"name":"Department for Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf , Martinistrasse 52, 20246 Hamburg , Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/Luebeck , Martinistrasse 52, 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco M","family":"Ojeda","sequence":"additional","affiliation":[{"name":"Department for Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf , Martinistrasse 52, 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Blankenberg","sequence":"additional","affiliation":[{"name":"Department for Cardiology, University Heart and Vascular Center Hamburg, 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