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Thromb Haemost 2010; 103(02): 435-441
DOI: 10.1160/TH09-06-0399
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Macrophage-modulating cytokines predict adverse outcome in heart failure

Philipp J. Hohensinner
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
2   Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
,
Kathrin Rychli
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Gerlinde Zorn
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Martin Hülsmann
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Rudolf Berger
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Deddo Mörtl
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Bernhard Richter
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Kurt Huber
2   Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
3   3rd Department of Medicine, Wilhelminenhospital, Vienna, Austria
,
Johann Wojta
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
2   Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
,
Richard Pacher
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Alexander Niessner
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
› Author Affiliations Financial support: The work of Philipp Hohensinner was supported by a fellowship of the Austrian Cardiology Society. The study was funded by the Association for the Promotion of Scientific Research – ATVB.
Further Information

Publication History

Received: 24 June 2009

Accepted after major revision: 06 January 2009

Publication Date:
22 November 2017 (online)

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Summary

Cytokines regulating the mobilisation, recruitment and survival of mononuclear cells may play an important role in progression of heart failure. Therefore, we investigated the role of granulocyte colony stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1) and macrophage colony stimulating factor (M-CSF) in patients with advanced heart failure. G-CSF, MCP-1 and M-CSF were determined in plasma of 351 patients with advanced heart failure by specific ELISAs. During a median follow up period of 16 months (95% confidence interval [CI]: 15–17 months) 175 patients (50%) experienced the composite endpoint rehospitalisation and all-cause mortality. M-CSF tertiles were associated with a gradually increasing risk with hazard ratios (HR) of 2.2 (95% CI: 1.5–3.2; for trend, p<0.001) for the composite endpoint and 2.6 (95% CI: 1.5–4.6; for trend, p=0.002) for all-cause mortality comparing third and first tertile. These associations remained significant in a multivariable Cox regression model after adjustment for BNP and other known risk factors (p=0.043 and p=0.024). High MCP-1 concentrations were associated with an increased risk of all-cause mortality with an adjusted HR of 1.9 (third vs. first tertile, 95% CI: 1.1–3.3; for trend, p=0.034). In contrast, G-CSF tertiles were not significantly associated with the composite endpoint or all-cause mortality in multivariable Cox regression. In conclusion, the independent and concentration-dependent association of macrophage-modulating cytokines and in particular of M-CSF with adverse outcome in advanced HF patients suggests that these cytokines may play an important pathophysiological role in progression of cardiomyopathy.

Keywords

Heart failure - cardiomyopathy - cytokines - macrophages

 

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