A screening method to spot biomarkers that may warn of serious events in a chronic disease - illustrated by cardiological CLARICOR trial data

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Per Winkel, University of Copenhagen
  • ,
  • Jørgen Hilden, University of Copenhagen
  • ,
  • Janus Christian Jakobsen, University of Copenhagen, Holbæk Hospital, University of Southern Denmark
  • ,
  • Jane Lindschou, University of Copenhagen
  • ,
  • Gorm Boje Jensen, University of Copenhagen
  • ,
  • Erik Kjøller, University of Copenhagen
  • ,
  • Ahmad Sajadieh, Bispebjerg Hospital
  • ,
  • Jens Kastrup, University of Copenhagen
  • ,
  • Hans Jørn Kolmos, University of Southern Denmark
  • ,
  • Anders Larsson, Uppsala University
  • ,
  • Johan Ärnlöv, Karolinska Institute
  • ,
  • Mette Bjerre
  • Christian Gluud, University of Copenhagen, University of Southern Denmark

OBJECTIVES: To develop a crude screening method for detecting biomarkers which frequently exhibit a rise (or fall) in level prior to a serious event (e.g. a stroke) in patients with a chronic disease, signalling that the biomarker may have an alarm-raising or prognostic potential. The subsequent assessment of the marker's clinical utility requires costly, difficult longitudinal studies. Therefore, initial screening of candidate-biomarkers is desirable.

METHODS: The method exploits a cohort of patients with biomarkers measured at entry and with recording of first serious event during follow-up. Copying those individual records onto a common timeline where a specific event occurs on the same day (Day 0) for all patients, the baseline biomarker level, when plotted against the patient's entry time on the revised timeline, will have a positive (negative) regression slope if biomarker levels generally rise (decline) the closer one gets to the event. As an example, we study 1,958 placebo-treated patients with stable coronary artery disease followed for nine years in the CLARICOR trial (NCT00121550), examining 11 newer biomarkers.

RESULTS: Rising average serum levels of cardiac troponin T and of N-terminal pro-B-type natriuretic peptide were seen prior to a fatal cardiovascular outcome. C-reactive protein rose prior to non-cardiovascular death. Glomerular filtration rate, seven lipoproteins, and nine newer cardiological biomarkers did not show convincing changes.

CONCLUSIONS: For early detection of biomarkers with an alarm-raising potential in chronic diseases, we proposed the described easy procedure. Using only baseline biomarker values and clinical course of participants with coronary heart disease, we identified the same cardiovascular biomarkers as those previously found containing prognostic information using longitudinal or survival analysis.

Original languageEnglish
JournalClinical Chemistry and Laboratory Medicine
Volume59
Issue11
Pages (from-to)1852-1860
Number of pages9
ISSN1434-6621
DOIs
Publication statusPublished - Oct 2021

    Research areas

  • biomarkers, cardiology, control charts, personalized medicine, reverse alignment, CLARITHROMYCIN, MORTALITY, ADJUDICATION, REGISTER, AGREEMENT, CORONARY-HEART-DISEASE, ARTERY-DISEASE

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