Temporal patterns of macrophage- and neutrophil-related markers are associated with clinical outcome in heart failure patients

Dominika Klimczak-Tomaniak, Elke Bouwens, Anne Sophie Schuurman, K. Martijn Akkerhuis, Alina Constantinescu, Jasper Brugts, B. Daan Westenbrink, Jan van Ramshorst, Tjeerd Germans, Leszek Pączek, Victor Umans, Eric Boersma, Isabella Kardys*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)


Aims: Evidence on the association of macrophage- and neutrophil-related blood biomarkers with clinical outcome in heart failure patients is limited, and, with the exception of C-reactive protein, no data exist on their temporal evolution. We aimed to investigate whether temporal patterns of these biomarkers are related to clinical outcome in patients with stable chronic heart failure (CHF). Methods and Results: In 263 patients with CHF, we performed serial plasma measurements of scavenger receptor cysteine-rich type 1 protein M130 (CD163), tartrate-resistant acid phosphatase type 5 (TRAP), granulins (GRN), spondin-1 (SPON1), peptidoglycan recognition protein 1 (PGLYRP1), and tissue factor pathway inhibitor (TFPI). The Cardiovascular Panel III (Olink Proteomics AB, Uppsala, Sweden) was used. During 2.2 years of follow-up, we collected 1984 samples before the occurrence of the composite primary endpoint (PE) or censoring. For efficiency, we selected 567 samples for the measurements (all baseline samples, the last two samples preceding the PE, and the last sample before censoring in event-free patients). The relationship between repeatedly measured biomarker levels and the PE was evaluated by joint models. Mean (±standard deviation) age was 67 ± 13 years; 189 (72%) were men; left ventricular ejection fraction (%) was 32 ± 11. During follow-up, 70 (27%) patients experienced the PE. Serially measured biomarkers predicted the PE in a multivariable model adjusted for baseline clinical characteristics [hazard ratio (95% confidence interval) per 1-standard deviation change in biomarker]: CD163 [2.07(1.47–2.98), P < 0.001], TRAP [0.62 (0.43–0.90), P = 0.009], GRN [2.46 (1.64–3.84), P < 0.001], SPON1 [3.94 (2.50–6.50), P < 0.001], and PGLYRP1 [1.62 (1.14–2.31), P = 0.006]. Conclusions: Changes in plasma levels of CD163, TRAP, GRN, SPON1, and PGLYRP1 precede adverse cardiovascular events in patients with CHF.

Original languageEnglish
Pages (from-to)1190-1200
Number of pages11
JournalESC heart failure
Issue number3
Publication statusPublished - 1 Jun 2020

Bibliographical note

Funding Information:
The Bio‐SHiFT study was supported by the Jaap Schouten Foundation (Rotterdam, the Netherlands) and the Noordwest Academie (Alkmaar, the Netherlands).

Publisher Copyright:
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology


Dive into the research topics of 'Temporal patterns of macrophage- and neutrophil-related markers are associated with clinical outcome in heart failure patients'. Together they form a unique fingerprint.

Cite this