Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals with diabetes mellitus

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Paul M. Haller
  • Alina Goßling
  • Christina Magnussen
  • Hermann Brenner
  • Ben Schöttker
  • Licia Iacoviello
  • Simona Costanzo
  • Frank Kee
  • Wolfgang Koenig
  • Linneberg, Allan René
  • Chaterina Sujana
  • Barbara Thorand
  • Veikko Salomaa
  • Teemu J. Niiranen
  • Stefan Söderberg
  • Henry Völzke
  • Marcus Dörr
  • Susana Sans
  • Teresa Padró
  • Stephan B. Felix
  • Matthias Nauck
  • Astrid Petersmann
  • Luigi Palmieri
  • Chiara Donfrancesco
  • Roberto De Ponti
  • Giovanni Veronesi
  • Marco M. Ferrario
  • Kari Kuulasmaa
  • Tanja Zeller
  • Francisco M. Ojeda
  • Stefan Blankenberg
  • Dirk Westermann
  • for the BiomarCaRE Consortium

Aims: 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. Methods and results: 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-Meier 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 < 0.001), accompanied by an increase in the c-index (increase to 0.81). Conclusion: 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.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Preventive Cardiology
Vol/bind30
Udgave nummer12
Sider (fra-til)1218-1226
Antal sider9
ISSN2047-4873
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The MORGAM Project has received funding from EU projects MORGAM (Biomed, BMH4-CT98-3183), GenomEUtwin (FP5, QLG2-CT-2002-01254), ENGAGE (FP7, HEALTH-F4-2007-201413), CHANCES (FP7, HEALTH-F3-2010-242244), BiomarCaRE (FP7, HEALTH-F2-2011-278913), euCanSHare (Horizon 2020, No. 825903), and AFFECT-EU (Horizon 2020, No. 847770); and Medical Research Council, London (G0601463, No. 80983: Biomarkers in the MORGAM Populations). This has supported central coordination, workshops, and part of the activities of the MORGAM Data Centre, the MORGAM Laboratories, and the MORGAM Participating Centres. SHIP is part of the Community Medicine Research Network of the University Medicine Greifswald, which is supported by the German Federal State of Mecklenburg—West Pomerania. The Brianza cohorts have been funded by the Health Administration of the Lombardia Region (Grant Nos. 17155/2004 and 10800/2009), and the latest follow-up activities were partially supported with grants from the Italian Ministry of Health [Grant 2012/597]. The KORA study was initiated and financed by the Helmholtz Zentrum München—German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Data collection in the KORA study is done in cooperation with the University Hospital of Augsburg.

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved.

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