Association between endothelial progenitor cell depletion in blood and mild-to-moderate renal insufficiency in stable angina.
BACKGROUND
Low blood counts of CD34/kinase-insert domain receptor double-positive cells (CD34(+)/KDR(+) cells)-a leukocytes subpopulation enriched for bone marrow-derived endothelial progenitor cells (EPC)- predict adverse outcomes in coronary artery disease (CAD). The dependence of EPC numbers on the glomerular filtration rate (GFR), another prognostic factor, has not been reported in CAD yet. Our aim was to assess CD34(+)/KDR(+) cell counts versus GFR in stable angina.


METHODS
We studied 102 stable angina men with severe angiographic CAD and normal left-ventricular systolic function. CD34(+)/KDR(+) cells were enumerated by flow cytometry.


RESULTS
With lowering GFR, CD34(+)/KDR(+) cell numbers (% of lymphocytes, median and interquartile range) decreased: 0.04 (0.03-0.06), 0.03 (0.02-0.05) and 0.02 (0.01-0.03)% for GFR >or=90, 60-89 and 30-59 ml/min/1.73 m(2), respectively (P < 0.001 for trend). CD34(+)/KDR(+) cell counts correlated with GFR (r = 0.25, P = 0.01), CAD extension score (r = -0.20, P = 0.04), soluble form of vascular cell adhesion molecule-1 (sVCAM-1) (r = -0.22, P = 0.03) and homocysteine (r = -0.20, P = 0.04) levels. A GFR <90 ml/min/1.73 m(2) was associated with insignificantly higher plasma erythropoietin concentrations (r = -0.22, P = 0.09 for trend) that correlated with haemoglobin levels (r = -0.33, P = 0.01, n = 59). The GFR-CD34(+)/KDR(+) cells relation was attenuated, yet maintained (beta = 0.19 +/- 0.09, P = 0.04) on adjustment for the remaining multivariate determinants of CD34(+)/KDR(+) cell numbers: sVCAM-1 (beta = -0.20 +/- 0.09, P = 0.03) and haemoglobin (beta = 0.18 +/- 0.09, P = 0.05).


CONCLUSIONS
Mild-to-moderate renal dysfunction accompanying stable angina is associated with CD34(+)/KDR(+) cell depletion, which partially depends on concomitant endothelial dysfunction and a tendency to anaemia (despite insignificantly higher erythropoietin) irrespective of an angiographic CAD extent. This may exacerbate an imbalance between endothelial injury and EPC-mediated repair, thus contributing to high cardiovascular risk in CAD coexisting with renal insufficiency.
Surdacki
Andrzej
A
2nd Department of Cardiology, Jagiellonian University, 17 Kopernika Street, 31-501 Cracow, Poland. surdacki.andreas@gmx.net
Marewicz
Ewa
E
Wieteska
Ewa
E
Szastak
Grzegorz
G
Rakowski
Tomasz
T
Wieczorek-Surdacka
Ewa
E
Dudek
Dariusz
D
Pryjma
Juliusz
J
Dubiel
Jacek S
JS
D000368:Aged; D000787:Angina Pectoris / Q000276:immunology / Q000473:pathology*; D018952:Antigens, CD34 / Q000378:metabolism*; D002452:Cell Count; D003324:Coronary Artery Disease / Q000453:epidemiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D051437:Renal Insufficiency / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D012307:Risk Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D018952:Antigens, CD34; D040301:Vascular Endothelial Growth Factor Receptor-2