TY - JOUR

T1 - A screening method to spot biomarkers that may warn of serious events in a chronic disease - illustrated by cardiological CLARICOR trial data

AU - Winkel, Per

AU - Hilden, Jørgen

AU - Jakobsen, Janus Christian

AU - Lindschou, Jane

AU - Jensen, Gorm Boje

AU - Kjøller, Erik

AU - Sajadieh, Ahmad

AU - Kastrup, Jens

AU - Kolmos, Hans Jorn

AU - Larsson, Anders

AU - Arnlov, Johan

AU - Bjerre, Mette

AU - Gluud, Christian

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - biomarkers

KW - cardiology

KW - control charts

KW - personalized medicine

KW - reverse alignment

KW - CORONARY-HEART-DISEASE

KW - ARTERY-DISEASE

KW - CLARITHROMYCIN

KW - ADJUDICATION

KW - AGREEMENT

KW - MORTALITY

KW - REGISTER

U2 - 10.1515/cclm-2021-0333

DO - 10.1515/cclm-2021-0333

M3 - Journal article

C2 - 34384145

VL - 59

SP - 1852

EP - 1860

JO - Clinical Chemistry and Laboratory Medicine

JF - Clinical Chemistry and Laboratory Medicine

SN - 1434-6621

IS - 11

ER -