title: The relationship of circulating endothelial cells to plasma indices of endothelial damage/dysfunction and apoptosis in acute coronary syndromes: implications for prognosis.
abstract: BACKGROUND
  While coronary artery disease has been linked to both endothelial damage and cellular apoptosis, their inter-relationships and impact on cardiovascular (CV) outcomes has been barely explored.
  
  
  OBJECTIVE
  First, we investigated the inter-relationships between circulating endothelial cells (CECs, and index of endothelial damage) and circulating plasma markers of endothelial damage/dysfunction [von Willebrand factor (VWF), soluble E selectin (sEsel)] and apoptosis [soluble Fas (sFas), Fas ligand (sFasL) and their ratio, sFas/sFasL] in patients presenting with acute coronary syndrome (ACS). Second, we assessed their prognostic values for major adverse CV events (MACE) in ACS.
  
  
  METHODS
  We studied 211 patients with ACS, who were compared with 60 healthy controls (HC) and 45 'disease controls' (patients with stable coronary artery disease, CAD). Simultaneous blood samples for CECs (immunobead method), VWF, sESel, sFas and sFasL (ELISA) were taken within 24 h of presentation of ACS and at 48 h post admission.
  
  
  RESULTS
  CEC, sEsel and VWF levels were significantly higher among the ACS groups compared with the CAD and HC (P < 0.05) groups. sFas was higher (P = 0.016) and sFasL lower (P = 0.021) in ACS compared with controls (HC and CAD). There was a significant increase in sFas/sFasL ratio with increasing disease severity (P = 0.0004). There were significant correlations between CECs and both VWF and sEsel (both P < 0.01) but no correlations between CECs and either sFas or sFas ligand. On univariate survival analysis, CECs were associated with an increased risk of both MACE [hazard ratio (HR) 2.4 (95% CI 1.2-4.1); P = 0.009] and cardiovascular death [HR 2.95 (95% CI 1.01-8.81); P = 0.047]. On multivariate Cox regression analysis, only VWF (and not CECs) remained as an independent predictor of MACE [HR 1.02 (95% CI 1.005-1.040); P = 0.009].
  
  
  CONCLUSIONS
  CECs were associated with abnormal plasma indices of endothelial damage/dysfunction and not apoptosis, despite abnormalities of all these markers being associated with ACS. VWF remained as an independent predictor of MACE, on multivariate analysis.
authors.affiliation: Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Boos
authors.forename: B
authors.initials: B
authors.lastname: Balakrishnan
authors.forename: A D
authors.initials: AD
authors.lastname: Blann
authors.forename: G Y H
authors.initials: GY
authors.lastname: Lip