G-CSF Predicts Cardiovascular Events in Patients with Stable Coronary Artery Disease.

Katharina M Katsaros,Johann Wojta,Stefan P Kastl,Walter S Speidl,Gerald Maurer,Serdar Farhan,Konstantin A Krychtiuk,Anna Wonnerth,Gerlinde Zorn,Kurt Huber,Ioannis Tentzeris,Svitlana Demyanets,Tobias Eckle

doi:10.1371/journal.pone.0142532

Abstract

Granulocyte-colony-stimulating-factor (G-CSF) induces mobilization of progenitor cells but may also exert pro-inflammatory and pro-thrombotic effects. Treatment with recombinant G-CSF after acute myocardial infarction is currently under examination and has been associated with in-stent restenosis. However, it is not known whether plasma levels of endogenous G-CSF are also associated with an increased cardiovascular risk. Therefore we included 280 patients with angiographically proven stable coronary artery disease. G-CSF was measured by specific ELISA and patients were followed for a median of 30 months for the occurrence of major adverse cardiovascular events (MACE: death, myocardial infarction, re-hospitalization). Those with cardiac events during follow-up showed significant higher G-CSF levels (32.3 pg/mL IQR 21.4–40.5 pg/mL vs. 24.6 pg/mL IQR 16.4–34.9 pg/mL; p<0.05) at baseline. Patients with G-CSF plasma levels above the median had a 2-fold increased risk for MACE (p<0.05). This was independent from established cardiovascular risk factors. In addition, G-CSF above the median was a predictor of clinical in-stent restenosis after implantation of bare-metal stents (6.6% vs. 19.4%; p<0.05) but not of drug-eluting stents (7.7% vs. 7.6%; p = 0.98). This data suggests that endogenous plasma levels of G-CSF predict cardiovascular events independently from established cardiac risk factors and are associated with increased in-stent restenosis rates after implantation of bare metal stents.

Highlights

Granulocyte-colony-stimulating-factor (G-CSF) is produced by monocytes, macrophages, fibroblasts, endothelial cells and bone marrow stromal cells, respectively
Further—as platelets are known to express G-CSF receptors—rising G-CSF plasma levels might result in a hyper-coagulable state due to increased platelet aggregation[3], which in turn might contribute to stent thrombosis, myocardial infarction and sudden death.[2]
Patients were maintained on aspirin 100 mg indefinitely, and clopidogrel 75 mg according to the guidelines of the European Society of Cardiology (ESC)

Summary

Introduction

Granulocyte-colony-stimulating-factor (G-CSF) is produced by monocytes, macrophages, fibroblasts, endothelial cells and bone marrow stromal cells, respectively. It induces mobilization of progenitor cells and acts as proliferative agent for stem cells. On the other side G-CSF has well known pro-inflammatory properties, which might be explained due to its ability in controlling neutrophil numbers as well as their activity during inflammation.[1] As a clinical consequence of inflammatory mechanisms instent-restenosis and progression of PLOS ONE | DOI:10.1371/journal.pone.0142532. Increased G-CSF Predicts Cardiovascular Events underlying coronary artery disease (CAD) might occur.[2] Further—as platelets are known to express G-CSF receptors—rising G-CSF plasma levels might result in a hyper-coagulable state due to increased platelet aggregation[3], which in turn might contribute to stent thrombosis, myocardial infarction and sudden death.[2]

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Results

Conclusion