Sleep-disordered breathing is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with decompensated systolic heart failure.
BACKGROUND
Sleep-disordered breathing (SDB) is known to occur frequently in and may predict worsening progression of patients with congestive heart failure (CHF). SDB is also known to play an important role in the development of idiopathic pulmonary arterial hypertension (PAH) via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin (OPG) and endothelial progenitor cells (EPCs). The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAH.


METHODS
EPCs were isolated, cultured, and quantified from CHF patients with SDB (n = 52), or without SDB (n = 68). OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP) from each group was analyzed and correlated with EPCs and the mean pulmonary artery pressure (mPAP) measured by right heart catheterization.


RESULTS
A significant decrease in circulating EPCs (29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/× 200 field; P < 0.05) was found in CHF patients with SDB compared to those without SDB. Both OPG (789.83 ± 89.38 vs. 551.29 ± 42.12 pg/mL; P < 0.05) and NT-proBNP (5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P < 0.05) were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP (50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P < 0.05). EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour (RDI, r = -0.45, P = 0.037) and blood level of OPG (r = -0.53, P = 0.011). Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RDI.


CONCLUSIONS
SDB due to hypoxemia from decompensated CHF is associated with (1) OPG elevation, (2) EPC depletion, and (3) mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.
Department of Cardiology, Huaihe Hospital of Henan University, No.8 Baogonghu Road, Kaifeng, Henan, China.
Han
H
Zhang
Department of Intensive Care Unit, Huaihe Hospital of Henan University, No.8 Baogonghu Road, Kaifeng, Henan, China.
Liu
L
Feng
Department of Cardiology, Huaihe Hospital of Henan University, No.8 Baogonghu Road, Kaifeng, Henan, China.
Qi-Lin
QL
Wan
Department of Cardiology, Huaihe Hospital of Henan University, No.8 Baogonghu Road, Kaifeng, Henan, China.
Yan
Y
Hong
Department of Cardiology, Huaihe Hospital of Henan University, No.8 Baogonghu Road, Kaifeng, Henan, China.
Yan-Ming
YM
Li
Department of Cardiology, Huaihe Hospital of Henan University, No.8 Baogonghu Road, Kaifeng, Henan, China.
Guan-Chang
GC
Cheng
Department of Cardiology, Huaihe Hospital of Henan University, No.8 Baogonghu Road, Kaifeng, Henan, China ; Reid Hospital and Health Care Services, Indiana University School of Medicine, Richmond, USA.
Xin-Qiang
XQ
Han
Congestive heart failure; Endothelial progenitor cells; Osteoprotegerin; Sleep-disordered breathing