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journal contribution
posted on 2020-05-14, 13:05authored byC Shi, HH van der Wal, HHW Silljé, MM Dokter, F van den Berg, L Huizinga, M Vriesema, J Post, SD Anker, JG Cleland, LL Ng, NJ Samani, K Dickstein, F Zannad, CC Lang, PL van Haelst, JA Gietema, M Metra, P Ameri, M Canepa, DJ van Veldhuisen, AA Voors, RA de Boer
BACKGROUND:There is increasing recognition that heart failure (HF) and cancer are conditions with a number of shared characteristics. OBJECTIVES:To explore the association between tumour biomarkers and HF outcomes. METHODS:In 2,079 patients of BIOSTAT-CHF cohort, we measured six established tumour biomarkers: CA125, CA15-3, CA19-9, CEA, CYFRA 21-1 and AFP. RESULTS:During a median follow-up of 21 months, 555 (27%) patients reached the primary end-point of all-cause mortality. CA125, CYFRA 21-1, CEA and CA19-9 levels were positively correlated with NT-proBNP quartiles (all P < 0.001, P for trend < 0.001) and were, respectively, associated with a hazard ratio of 1.17 (95% CI 1.12-1.23; P < 0.0001), 1.45 (95% CI 1.30-1.61; P < 0.0001), 1.19 (95% CI 1.09-1.30; P = 0.006) and 1.10 (95% CI 1.05-1.16; P < 0.001) for all-cause mortality after correction for BIOSTAT risk model (age, BUN, NT-proBNP, haemoglobin and beta blocker). All tumour biomarkers (except AFP) had significant associations with secondary end-points (composite of all-cause mortality and HF hospitalization, HF hospitalization, cardiovascular (CV) mortality and non-CV mortality). ROC curves showed the AUC of CYFRA 21-1 (0.64) had a noninferior AUC compared with NT-proBNP (0.68) for all-cause mortality (P = 0.08). A combination of CYFRA 21-1 and NT-proBNP (AUC = 0.71) improved the predictive value of the model for all-cause mortality (P = 0.0002 compared with NT-proBNP). CONCLUSIONS:Several established tumour biomarkers showed independent associations with indices of severity of HF and independent prognostic value for HF outcomes. This demonstrates that pathophysiological pathways sensed by these tumour biomarkers are also dysregulated in HF.
Funding
We thank all BIOSTAT participants and investigators. This study was funded by grant from theEuropean Research Council (ERC CoG 818715, SECRETE‐HF) and the European Commission (FP7‐242209‐BIOSTAT‐CHF).Canxia Shi is supported with a scholarship from the China Scholarship Council [CSC number: 201806170057]. Dr. de Boer is furthermore supported by the Dutch Heart Foundation [CVON DOSIS, grant 2014‐40, CVON SHE‐PREDICTS‐HF, grant 2017‐21; CVON RED‐CVD, grant 2017‐11; and CVON PREDICT2, grant 2018‐30]; and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research [NWO VIDI, grant 917·13·350], and by a grant from the Leducq Foundation [Cure PhosphoLambaN‐induced Cardiomyopathy (Cure‐PLaN)]. We would like to thank Roche Diagnostics for providing reagents to measure the tumour biomarkers (Dr. K van Lynden, Roche Diagnostics BV, the Netherlands).
History
Citation
Shi, C, van der Wal, HH, Silljé, HHW, Dokter, MM, van den Berg, F, Huizinga, L, Vriesema, M, Post, J, Anker, SD, Cleland, JG, Ng, LL, Samani, NJ, Dickstein, K, Zannad, F, Lang, CC, van Haelst, PL, Gietema, JA, Metra, M, Ameri, P, Canepa, M, van Veldhuisen, DJ, Voors, AA, de Boer, RA (University Medical Center Groningen, Groningen, the Netherlands; Universitätsmedizin Berlin, Berlin, Germany; Imperial College, London, UK; University of Glasgow, Glasgow; University of Leicester, Leicester; Glenfield Hospital, Leicester, UK; Stavanger University Hospital, Stavanger, Norway; Centre Hospitalier Regional et Universitaire de Nancy, Vandoeuvre les Nancy, France; University of Dundee, Dundee, UK; F. Hoffmann‐La Roche Ltd. Diagnostics Division, Basel, Switzerland; University Medical Center Groningen, Groningen, the Netherlands; University of Brescia, Brescia; IRCCS Ospedale Policlinico San Martino, Genova; University of Genova, Genova, Italy. Tumour biomarkers: association with heart failure outcomes. J Intern Med; 2020; 00: 1– 12. https://doi.org/10.1111/joim.13053