Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study

Paul Welsh, Lei Kou, Changhong Yu, Inder Anand, Dirk J. van Veldhuisen, Aldo P. Maggioni, Akshay S. Desai, Scott D. Solomon, Marc A. Pfeffer, Sunfa Cheng, Lars Gullestad, Pål Aukrust, Thor Ueland, Karl Swedberg, James B. Young, Michael W. Kattan, Naveed Sattar, John J.V. McMurray

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Aims: To test the prognostic value of emerging biomarkers in the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial. Methods and results: Circulating cardiac [N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT)], neurohumoral [mid-regional pro-adrenomedullin (MR-proADM) and copeptin], renal (cystatin C), and inflammatory [high-sensitivity C-reactive protein (hsCRP)] biomarkers were measured at randomization in 1853 participants with complete data. The relationship between these biomarkers and the primary composite endpoint of heart failure hospitalization or cardiovascular death over 28 months of follow-up (n = 834) was evaluated using Cox proportional hazards regression, the c-statistic and the net reclassification index (NRI). After adjustment, the hazard ratio (HR) for the composite outcome in the top tertile of the distribution compared to the lowest tertile for each biomarker was: NT-proBNP 3.96 (95% CI 3.16–4.98), hsTnT 3.09 (95% CI 2.47–3.88), MR-proADM 2.28 (95% CI 1.83–2.84), copeptin 1.66 (95% CI 1.35–2.04), cystatin C 1.92 (95% CI 1.55–2.37), and hsCRP 1.51 (95% CI 1.27–1.80). A basic clinical prediction model was improved on addition of each biomarker individually, most strongly by NT-proBNP (NRI +62.3%, P < 0.001), but thereafter was only improved marginally by addition of hsTnT (NRI +33.1%, P = 0.004). Further addition of biomarkers did not improve discrimination further. Findings were similar for all-cause mortality. Conclusion: Once NT-proBNP is included, only hsTnT moderately further improved risk stratification in this group of chronic heart failure with reduced ejection fraction patients with moderate anaemia. NT-proBNP and hsTnT far outperform other emerging biomarkers in prediction of adverse outcome.

Original languageEnglish (US)
Pages (from-to)268-277
Number of pages10
JournalEuropean Journal of Heart Failure
Volume20
Issue number2
DOIs
StatePublished - Feb 1 2018

Keywords

  • Adrenomedullin
  • Copeptin
  • Cystatin C
  • Heart failure
  • Natriuretic peptides
  • Troponin

PubMed: MeSH publication types

  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

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    Welsh, P., Kou, L., Yu, C., Anand, I., van Veldhuisen, D. J., Maggioni, A. P., Desai, A. S., Solomon, S. D., Pfeffer, M. A., Cheng, S., Gullestad, L., Aukrust, P., Ueland, T., Swedberg, K., Young, J. B., Kattan, M. W., Sattar, N., & McMurray, J. J. V. (2018). Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study. European Journal of Heart Failure, 20(2), 268-277. https://doi.org/10.1002/ejhf.988