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Open Access Research article

Association of soluble endothelial protein C receptor plasma levels and PROCR rs867186 with cardiovascular risk factors and cardiovascular events in coronary artery disease patients: The Athero Gene Study

Choumous Kallel1, William Cohen1, Noémie Saut1, Stefan Blankenberg2, Renate Schnabel2, Hans J Rupprecht3, Christoph Bickel4, Thomas Munzel3, David-Alexandre Tregouet5 and Pierre-Emmanuel Morange1*

Author Affiliations

1 INSERM UMR_1062, Aix-Marseille Université, Marseille, F-13385, France

2 Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany

3 Department of Medicine II, Johannes Gutenberg-University Mainz, Mainz, Germany

4 Federal Armed Forces Central Hospital Koblenz, Koblenz, Germany

5 INSERM, UMR_S 937; Institute of Cardiometabolism And Nutrition (ICAN), Université Pierre et Marie Curie Paris 6, Paris, F-75013, France

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BMC Medical Genetics 2012, 13:103  doi:10.1186/1471-2350-13-103

Published: 8 November 2012

Abstract

Background

Blood coagulation is an essential determinant of coronary artery disease (CAD). Soluble Endothelial Protein C Receptor (sEPCR) may be a biomarker of a hypercoagulable state. We prospectively investigated the relationship between plasma sEPCR levels and the risk of cardiovascular events (CVE).

Methods

We measured baseline sEPCR levels in 1673 individuals with CAD (521 with acute coronary syndrome [ACS] and 1152 with stable angina pectoris [SAP]) from the AtheroGene cohort. During a median follow up of 3.7 years, 136 individuals had a CVE. In addition, 891 of these CAD patients were genotyped for the PROCR rs867186 (Ser219Gly) variant.

Results

At baseline, sEPCR levels were similar in individuals with ACS and SAP (median: 111 vs. 115 ng/mL respectively; p=0.20). Increased sEPCR levels were found to be associated with several cardiovascular risk factors including gender (p=0.006), soluble Tissue Factor levels (p=0.0001), diabetes (p=0.0005), and factors reflecting impaired renal function such as creatinine and cystatin C (p<0.0001). sEPCR levels were not significantly associated with the risk of CVE (median: 110 and 114 ng/mL in individuals with and without future CVE respectively; p=0.68). The rs867186 variant was found to explain 59% of sEPCR levels variability (p<10-200) but did not associate with CVE risk.

Conclusion

Our findings show that in patients with CAD, circulating sEPCR levels are related to classical cardiovascular risk factors and renal impairment but are not related to long-term incidence of CVE.

Keywords:
\; Haemostasis; Protein C; Endothelial protein C receptor; Coronary artery disease