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

• Main Authors: Kallel Choumous, Cohen William, Saut Noémie, Blankenberg Stefan, Schnabel Renate, Rupprecht Hans J, Bickel Christoph, Munzel Thomas, Tregouet David-Alexandre, Morange Pierre-Emmanuel
• Format: Article
• Language: English
• Published: BMC 2012-11-01
• Series: BMC Medical Genetics
• Subjects: Haemostasis; Protein C; Endothelial protein C receptor; Coronary artery disease
• Online Access: http://www.biomedcentral.com/1471-2350/13/103

<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Methods</p> <p>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 Athero<it>Gene</it> 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 <it>PROCR</it> rs867186 (Ser219Gly) variant.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>