Clinical Research in Cardiology

, Volume 108, Issue 2, pp 133–141 | Cite as

T cell and monocyte/macrophage activation markers associate with adverse outcome, but give limited prognostic value in anemic patients with heart failure: results from RED-HF

  • Aurelija Abraityte
  • Pål Aukrust
  • Lei Kou
  • Inder S. Anand
  • James Young
  • John J. V. Mcmurray
  • Dirk J. van Veldhuisen
  • Lars Gullestad
  • Thor UelandEmail author
Original Paper



Activated leukocytes may contribute to the development and progression of heart failure (HF). We investigated the predictive value of circulating levels of stable and readily detectable markers reflecting both monocyte/macrophage and T-cell activity, on clinical outcomes in HF patients with reduced ejection fraction (HFrEF).


The association between baseline plasma levels of soluble CD163 (sCD163), macrophage migration inhibitory factor (MIF), granulysin, soluble interleukin-2 receptor (sIL-2R), and activated leukocyte cell adhesion molecule (ALCAM) and the primary endpoint of death from any cause or first hospitalization for worsening of HF was evaluated using multivariable Cox proportional hazard models in 1541 patients with systolic HF and mild to moderate anemia, enrolled in the Reduction of Events by darbepoetin alfa in Heart Failure (RED-HF) trial. Modifying effects and interaction with darbepoetin alfa treatment were also assessed.


All leukocyte markers, except granulysin, were associated with the primary outcome and all-cause death in univariate analysis (all p < 0.01) and remained significantly associated in multivariable analysis adjusting for conventional clinical variables (e.g. age, gender, BMI, NYHA class, creatinine, LVEF, etiology) and CRP. However, after final adjustment for TnT and NT-proBNP no associations were found with outcomes. No interaction with darbepoetin alpha treatment was observed for any marker.


Leukocyte activation markers sCD163, MIF, sIL-2R, and ALCAM were associated with adverse outcome in patients with HFrEF, but add little as prognostic markers on top of established biochemical risk markers.


Leukocyte Monocyte Macrophage T cell Heart failure Prognosis 


Compliance with ethical standards

Conflict of interest

Inder Anand, John J. V. Mcmurray, Dirk J. van Veldhuisen and James Young are members of the RED-HF Executive Committee—no payments in the last 12 months. John J. V. Mcmurray has received travel and accommodation costs paid by Cytokinetics/Amgen in relation to advisory board and clinical trial meetings about omecamtiv mecarbil.

Supplementary material

392_2018_1331_MOESM1_ESM.docx (384 kb)
Supplementary material 1 (DOCX 383 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Aurelija Abraityte
    • 1
    • 4
    • 5
  • Pål Aukrust
    • 1
    • 3
    • 4
    • 6
  • Lei Kou
    • 8
  • Inder S. Anand
    • 9
  • James Young
    • 8
  • John J. V. Mcmurray
    • 10
  • Dirk J. van Veldhuisen
    • 11
  • Lars Gullestad
    • 2
    • 5
  • Thor Ueland
    • 1
    • 4
    • 7
    Email author
  1. 1.Research Institute of Internal MedicineOslo University HospitalOsloNorway
  2. 2.Department of CardiologyOslo University HospitalOsloNorway
  3. 3.Section of Clinical Immunology and Infectious DiseasesOslo University HospitalOsloNorway
  4. 4.Faculty of MedicineUniversity of OsloOsloNorway
  5. 5.Center for Heart Failure ResearchUniversity of OsloOsloNorway
  6. 6.K. G. Jebsen Inflammation Research CenterUniversity of OsloOsloNorway
  7. 7.K. G. Jebsen Thrombosis Research and Expertise CenterUniversity of TromsøTromsöNorway
  8. 8.Cleveland Clinic FoundationClevelandUSA
  9. 9.VA Medical Center and University of MinnesotaMinneapolisUSA
  10. 10.BHF Glasgow Cardiovascular Research CentreUniversity of GlasgowGlasgowUK
  11. 11.University Medical Center GroningenGroningenThe Netherlands

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