Prognostic value of 12 novel cardiological biomarkers in stable coronary artery disease. A 10-year follow-up of the placebo group of the Copenhagen CLARICOR trial

Per Winkel, Janus Christian Jakobsen, Jørgen Hilden, Gorm Boje Jensen, Erik Kjøller, Ahmad Sajadieh, Jens Kastrup, Hans Jørn Kolmos, Kasper Karmark Iversen, Mette Bjerre, Anders Larsson, Johan Ärnlöv, Christian Gluud, Per Winkel, Janus Christian Jakobsen, Jørgen Hilden, Gorm Boje Jensen, Erik Kjøller, Ahmad Sajadieh, Jens Kastrup, Hans Jørn Kolmos, Kasper Karmark Iversen, Mette Bjerre, Anders Larsson, Johan Ärnlöv, Christian Gluud

Abstract

Objective: To assess if 12 novel circulating biomarkers, when added to 'standard predictors' available in general practice, could improve the 10-year prediction of cardiovascular events and mortality in patients with stable coronary heart disease.

Design: The patients participated as placebo receiving patients in the randomised clarithromycin for patients with stable coronary artery disease (CLARICOR) trial at a random time in their disease trajectory.

Setting: Five Copenhagen University cardiology departments and a coordinating centre.

Participants: 1998 participants with stable coronary artery disease.

Outcomes: Death and composite of myocardial infarction, unstable angina pectoris, cerebrovascular disease and death.

Results: When only 'standard predictors' were included, 83.4% of all-cause death predictions and 68.4% of composite outcome predictions were correct. Log(calprotectin) and log(cathepsin-S) were not associated (p≥0.01) with the outcomes, not even as single predictors. Adding the remaining 10 biomarkers (high-sensitive assay cardiac troponin T; neutrophil gelatinase-associated lipocalin; osteoprotegerin; N-terminal pro-B-type natriuretic peptide; tumour necrosis factor receptor 1 and 2; pregnancy-associated plasma protein A; endostatin; YKL40; cathepsin-B), which were all individually significantly associated with the prediction of the two outcomes, increased the figures to 84.7% and 69.7%.

Conclusion: When 'standard predictors' routinely available in general practices are used for risk assessment in consecutively sampled patients with stable coronary artery disease, the addition of 10 novel biomarkers to the prediction model improved the correct prediction of all-cause death and the composite outcome by <1.5%.

Trial registration number: NCT00121550.

Keywords: biomarker; cardiology; coronary heart disease.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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