Atorvastatin treatment improves endothelial function through endothelial progenitor cells mobilization in ischemic heart failure patients

• Published in: Atherosclerosis Vol. 238; no. 2; pp. 159 - 164
• Main Authors: Oikonomou, Evangelos, Siasos, Gerasimos, Zaromitidou, Marina, Hatzis, George, Mourouzis, Konstantinos, Chrysohoou, Christine, Zisimos, Konstantinos, Mazaris, Savvas, Tourikis, Panagiotis, Athanasiou, Dimitris, Stefanadis, Christodoulos, Papavassiliou, Athanasios G, Tousoulis, Dimitris
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.02.2015
• Subjects: AC133 Antigen; Aged; Aged, 80 and over; Antigens, CD - blood; Antigens, CD34 - blood; Atorvastatin Calcium; Biomarkers - blood; Brachial Artery - drug effects; Brachial Artery - metabolism; Brachial Artery - pathology; Brachial Artery - physiopathology; Cardiovascular; Cell Movement - drug effects; Cross-Over Studies; Double-Blind Method; Endothelial function; Endothelial progenitor cells; Endothelial Progenitor Cells - drug effects; Endothelial Progenitor Cells - metabolism; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Female; Glycoproteins - blood; Greece; Heart failure; Heart Failure - blood; Heart Failure - diagnosis; Heart Failure - drug therapy; Heart Failure - etiology; Heart Failure - physiopathology; Heptanoic Acids - therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Inflammation Mediators - blood; Male; Middle Aged; Myocardial Ischemia - complications; Myocardial Ischemia - diagnosis; Peptides - blood; Pyrroles - therapeutic use; Recovery of Function; Statins; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha - blood; Vascular Endothelial Growth Factor Receptor-2 - blood; Vasodilation - drug effects; Heart failure; Endothelial function; Statins; Endothelial progenitor cells; Endothelium
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2014.12.014

Abstract Objective : Endothelial function is an independent predictor of prognosis in heart failure (HF) subjects. Statins, beyond their lipid lowering role, exert beneficial effect in patients with atherosclerosis. In the present study we examined the impact of low and intermediate dose atorvastatin treatment on endothelial function, bone marrow-derived endothelial progenitor cells (EPC) mobilization and inflammatory status according to HF patient status. Methods : We studied the effect of 4 weeks administration of atorvastatin in 26 patients with ischemic HF. The study was carried out on two separate arms, one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d (randomized, double-blind, cross-over design). The number of circulating CD34(+)/CD133(+)/KDR(+) EPCs was evaluated by flow cytometry. Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery. Serum levels of tumor necrosis factor alpha (TNF-α) were measured by ELISA. Results : Treatment with atorvastatin 40 mg/d significantly increased circulating EPC ( p  = 0.002), FMD ( p  = 0.001) and reduced TNF-α ( p  = 0.01) compared to baseline. Similarly, treatment with atorvastatin 10 mg/day increased circulating EPC ( p  = 0.01), FMD ( p  = 0.08) and reduced TNF-α ( p  = 0.01) compared to baseline. Interestingly, with 40 mg/day atorvastatin treatment the increase in EPC was higher in subjects categorized as NYHA class II compared to subjects categorized as NYHA class III ( p  = 0.03). Conclusions : Our results confirmed the distinct impact of atorvastatin treatment on the restoration of endothelial function due to EPC mobilization in ischemic HF subjects. Moreover, these findings provide the potential clinical significance of EPC status monitoring to individualize treatment in HF subjects.