Changes in circulating progenitor cells are associated with outcome in heart failure patients: a longitudinal study.
BACKGROUND
Circulating progenitor cells (CPCs) are involved in the process of endothelial repair and are a prognostic factor in cardiovascular diseases. We evaluated the association between serial measurements of CPCs and functional capacity and outcomes in heart failure (HF).


METHODS
We included 156 consecutive consenting ambulatory HF patients (left ventricular ejection fraction < 40%). We evaluated CPCs and functional capacity (peak VO2) every 6 months for up to 2 years. CPCs were measured as early-outgrowth colony-forming units (EO-CFUs) and circulating CD34+, VEGFR2+ and/or CD133+ cells. We recorded mortality, HF hospital admissions, transplant, and ventricular assist device.


RESULTS
The mean age was 55 ± 15 years. A decrease in CD34+VEGFR2+ cells was independently associated with increased functional capacity; a 10-cell decrease in CD34+VEGFR2+ cells was associated with an increase of 0.2 mL/kg/min in peak VO2 (P < 0.05). We found an interaction effect (P = 0.02) between EO-CFUs and diabetes: in patients without diabetes, a 10-EO-CFU increase was independently associated with increased peak VO2 of 0.28 mL/kg/min (P = 0.01), and in patients with diabetes, a decrease in EO-CFUs was associated with an increased peak VO2 (P < 0.05). Higher EO-CFUs were associated with reduced mortality (hazard ratio, 0.25; 95% confidence interval, 0.09-0.69).


CONCLUSIONS
We noted differential relations between CPCs and outcomes in patients with vs without diabetes. Higher EO-CFUs and lower CD34+VEGFR2+ cells were associated with improved functional capacity and reduced mortality in nondiabetic patients. In patients with diabetes, lower EO-CFUs were associated with improved functional capacity. The basis for these differences requires further examination.
Heart Failure/Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. Electronic address: Carolina.alba@uhn.ca.
Ana C
AC
Alba
Spencer D
SD
Lalonde
Vivek
V
Rao
Stephen D
SD
Walter
Gordon H
GH
Guyatt
Heather J
HJ
Ross
D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D002452:Cell Count; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006333:Heart Failure / Q000401:mortality / Q000473:pathology*; D016027:Heart Transplantation / Q000706:statistics & numerical data; D006353:Heart-Assist Devices / Q000706:statistics & numerical data; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009864:Ontario; D010100:Oxygen / Q000097:blood; D010343:Patient Admission / Q000706:statistics & numerical data; D063868:Patient Outcome Assessment; D010455:Peptides / Q000097:blood; D011379:Prognosis; D013234:Stem Cells / Q000473:pathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000401:mortality / Q000473:pathology
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D040301:Vascular Endothelial Growth Factor Receptor-2; D010100:Oxygen