Tumor biomarkers: association with heart failure outcomes

Canxia Shi, Haye H. van der Wal, H. H. W. Silljé , Martin Dokter, Freek van den Berg, Leon Huizinga, Michelle Vriesema, Joliene Post, Stefan D. Anker, John G. F. Cleland, Leong Loke Ng, Nilesh J. Samani, Kenneth Dickstein, Faiez Zannad, Chim Lang, Paul L. van Haelst, Jourik A. Gietema , Marco Metra, Pietro Ameri , Marco Canepa Dirk Jan van Veldhuisen, Adriaan A. Voors, Rudolf A. de Boer

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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 tumor biomarkers and HF outcomes. Methods: In 2,079 patients of BIOSTAT-CHF cohort, we measured six established tumor 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 endpoint 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, hemoglobin, and beta-blocker). All tumor biomarkers (except AFP) had significant associations with secondary endpoints (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 non-inferior AUC compared to 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 to NT-proBNP). Conclusions: Several established tumor 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 tumor biomarkers are also dysregulated in HF.
Original languageEnglish
Pages (from-to)207-218
Number of pages12
JournalJournal of Internal Medicine
Issue number2
Early online date5 May 2020
Publication statusPublished - 1 Aug 2020


  • Heart failure
  • Neoplasms
  • Biomarkers
  • tumor
  • Natriuretic peptides


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