title: Circulating CD34+ progenitor cells and risk of mortality in a population with coronary artery disease.
abstract: BACKGROUND
  Low circulating progenitor cell numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis.
  
  
  OBJECTIVE
  To investigate whether low numbers of progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk.
  
  
  RESULTS
  Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD45(med+) blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary end point of all-cause death. There was an inverse association between CD34(+) and CD34(+)/CD133(+) cell counts and risk of death in cohort 1 (β=-0.92, P=0.043 and β=-1.64, P=0.019, respectively) that was confirmed in cohort 2 (β=-1.25, P=0.020 and β=-1.81, P=0.015, respectively). Covariate-adjusted hazard ratios in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34(+)/CD133(+) cell counts improved risk prediction metrics beyond standard risk factors.
  
  
  CONCLUSIONS
  Reduced circulating progenitor cell counts, identified primarily as CD34(+) mononuclear cells or its subset expressing CD133, are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction, and cell selection for cell-based therapies.
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.|Institute of Cardiovascular Sciences, University College London, London, UK.
authors.forename: Riyaz S
authors.initials: RS
authors.lastname: Patel
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Qunna
authors.initials: Q
authors.lastname: Li
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Nima
authors.initials: N
authors.lastname: Ghasemzadeh
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eapen
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Lauren D
authors.initials: LD
authors.lastname: Moss
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: A Umair
authors.initials: AU
authors.lastname: Janjua
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Manocha
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Hatem Al
authors.initials: HA
authors.lastname: Kassem
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.|Dept of Medicine, Baptist Health South Florida, Florida, USA.
authors.forename: Emir
authors.initials: E
authors.lastname: Veledar
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Habib
authors.initials: H
authors.lastname: Samady
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: W Robert
authors.initials: WR
authors.lastname: Taylor
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.|Dept of Medicine, Baptist Health South Florida, Florida, USA.|Dept. of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA, USA.
authors.forename: A Maziar
authors.initials: AM
authors.lastname: Zafari
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Sperling
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.|Dept. of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, GA, USA.
authors.forename: Viola
authors.initials: V
authors.lastname: Vaccarino
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.affiliation: Dept. of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000097:blood*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D016037:Single-Blind Method; D013234:Stem Cells / Q000378:metabolism*; D015996:Survival Rate / Q000639:trends; D055815:Young Adult
chemical_list: D018952:Antigens, CD34
keywords: antigen CD34; biomarkers; coronary artery disease; flow cytometry; outcome assessment (health care); prognosis; risk; stem cells