European Heart Journal Advance Access published online on April 21, 2007
European Heart Journal, doi:10.1093/eurheartj/ehm070
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Relationship between circulating endothelial cells and the predicted risk of cardiovascular events in acute coronary syndromes
Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH UK
Received 11 December 2006; revised 26 February 2007; accepted 8 March 2007.
* Corresponding author. Tel: +44 121 5074403; fax: +44 121 5544083. E-mail address: g.y.h.lip{at}bham.ac.uk
Aims: The quantification of circulating endothelial cells (CECs) in whole blood is a novel marker of direct endothelial injury and shows promise as a potential biomarker of cardiovascular (CV) risk. The inter-relationship(s) between CECs and predicted CV risk has not been explored in large cohort of ‘high-risk’ patients. We hypothesized that there would be a significant relationship between increasing CEC counts and predicted CV risk in a broad spectrum of patients presenting with acute coronary syndrome (ACS).
Methods and results: We studied 197 patients (aged 40–80 years) admitted with a confirmed diagnosis of unstable angina (UA), non-ST-elevation myocardial infarction (MI, NSTEMI), or ST-elevation MI (STEMI). CEC counts were performed on venous whole blood using the immunobead technique. Four well-validated ACS risk scores [(PURSUIT and TIMI for NSTEMI/UA) TIMI (STEMI) and GRACE (all ACS)] were calculated from the initial clinical history and electrocardiogram, as well as from values of laboratory parameters collected within 12 h of admission. We included a healthy control (HC) group of 50 matched patients in order to quantify the accuracy of CEC counts for the diagnosis of ACS and to compare disease vs. HC counts. CEC counts were significantly higher in the disease group when compared with the HC group. CEC counts significantly increased with increasing severity of disease (that is, UA vs. NSTEMI vs. STEMI; P = 0.002). CEC counts were higher among patients with clinical evidence of heart failure (Killip Class II–IV) when compared with those without (Killip Class I) on admission (P < 0.0001). There was a significant correlation between CEC counts and predicted CV risk for each of the four ACS risk scoring schemes (all P < 0.05). The area under the receiver-operating characteristic (ROC) curve (AUC) for the entire ACS cohort was 0.82 (95% CI: 0.76–0.88; P < 0.0001). A CEC count of 
7/mL provided a positive predictive value of 90.6% (95% CI: 85.6–95.7%) and a negative predictive value of 53.5% (41.9–65.1%) for the diagnosis of MI (NSTEMI/STEMI) in the presence of an appropriate clinical presentation.
Conclusion: There is a significant and positive correlation between increasing CECs and increasing CV risk in ACS. The diagnostic accuracy of CECs in this setting is only ‘moderate’. Whilst it is good at confirming the presence of MI, a CEC value of <7.0/mL is less reliable at confidently excluding patients without disease.
Key Words: Circulating endothelial cells • Cardiovascular risk • Outcome • Myocardial infarction • Acute coronary syndromes • Risk scores
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