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Complement anaphylatoxin C3a as a novel independent prognostic marker in heart failure

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Abstract

Objectives

The purpose of this study was to evaluate complement activation in a heart failure cohort. Based on their powerful biological activity, we hypothesized that the levels of anaphylatoxin C3a are related to pathological signs and outcomes in heart failure.

Design, setting and patients

Complement activation products C3a and SC5b9 were determined in 182 consecutive CHF patients (single centre, prospective cohort study), with a left ventricular ejection fraction <45%. Mortality and re-hospitalisation due to the progression of CHF were assessed after a median follow-up of 14 months.

Interventions

None.

Results

In the univariate analysis, high level of anaphylatoxin C3a was significantly associated with clinical events (p < 0.0001), whereas SC5b9 showed a tendency of association (p = 0.094). In multivariable Cox analysis, adjusted for age, NT-proBNP, diastolic blood pressure, body mass index (BMI), haemoglobin and creatinine levels, C3a was a significant predictor of HF-related re-hospitalization or death (HR 1.189 per 1-SD increase, 95% CI 1.023–1.383), and of cardiovascular events or death (HR 1.302, CI 1.083–1.566). C3a was strongly associated with the presence of peripheral oedema, inflammatory markers (CRP, prealbumin, IL-6, sTNFRI, sTNFRII), heat-shock protein 70 levels and endothelial activation markers (von-Willebrand factor and endothelin-1).

Conclusions

Results of the present study showed that complement activation is strongly linked to unfavourable outcomes in heart failure. High levels of anaphylatoxin C3a predicted re-hospitalization, cardiovascular events and mortality in adjusted survival model. Increased C3a levels were associated with biomarkers of acute-phase reaction, inflammation, cellular stress response, endothelial-cell activation and oedematous complications independently from disease severity.

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Acknowledgments

We are grateful to our patients who agreed to participate in this study. The skilful technical assistance of Holeczky Rudolfné, Szigeti Antalné, Korponai Gézáné, Piroska Sturmann and Márta Kókai is acknowledged with many thanks. This work was supported by the following grants: Hungarian Scientific Research Fund (OTKA T046837, NF72689), National Development Agency TÁMOP 4.2.2-08/01/KMR-2008-0004 and Ministry of Health (ETT 229/2006).

Conflict of interest

Dr Kunde is employee of BRAHMS GmbH (now Thermofisher), Hennigsdorf, Germany that commercializes immunoassays and has developed the CT-proET-1 assay, for which it owns patent rights. The present study was not financed by BRAHMS AG. The remaining authors report no conflicts.

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Authors and Affiliations

  1. IIIrd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, Budapest, 1125, Hungary

    Tímea Gombos, Zsolt Förhécz, Zoltán Pozsonyi, George Füst, Lívia Jánoskuti, István Karádi & Zoltán Prohászka

  2. Research Group of Inflammation Biology and Immunogenomics, Hungarian Academy of Sciences, Budapest, Hungary

    Zoltán Prohászka

  3. Heart Center, Semmelweis University, Budapest, Hungary

    Gábor Széplaki

  4. Department of Global Medical Affairs, BRAHMS GmbH, Neuendorfstr. 25, 16761, Hennigsdorf, Germany

    Jan Kunde

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  1. Tímea Gombos
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  2. Zsolt Förhécz
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  4. Gábor Széplaki
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  5. Jan Kunde
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  7. Lívia Jánoskuti
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  8. István Karádi
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  9. Zoltán Prohászka
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Correspondence to Zoltán Prohászka.

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Gombos, T., Förhécz, Z., Pozsonyi, Z. et al. Complement anaphylatoxin C3a as a novel independent prognostic marker in heart failure. Clin Res Cardiol 101, 607–615 (2012). https://doi.org/10.1007/s00392-012-0432-6

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  • DOI: https://doi.org/10.1007/s00392-012-0432-6

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