title: Nebivolol therapy improves endothelial function and increases exercise tolerance in patients with cardiac syndrome X.
abstract: OBJECTIVE
  We sought to determine whether nebivolol affects coronary endothelial function and exercise induced ischemia in patients with cardiac syndrome X (CSX).
  
  
  METHODS
  The study protocol undertaken was based on a single-blind randomized controlled prospective study. After a 2-week washout period, 38 patients with cardiac syndrome X were randomized to receive either nebivolol 5 mg daily (n=19) or metoprolol 50 mg daily (n=19) in a single- blind design for 12 weeks. The control group under study was consisted of 16 age- and gender-matched subjects with negative treadmill exercise tests. Plasma endothelial nitric oxide (NOx), L-arginine, and asymmetric dimethylarginine (ADMA) were measured in all patients at baseline and after 12 weeks of treatment. Statistical differences among groups were tested by one-way analysis of variance and unpaired samples t test for parametric; Kruskal-Wallis and Mann-Whitney U tests for non-parametric variables, respectively. A paired samples t test was used to compare continuous variables before and after drug therapy.
  
  
  RESULTS
  At baseline, plasma level of NOx, L-arginine, and L-arginine/ADMA ratio were lower (p<0.001 for all) in patients with CSX than in the control patients. Whereas, the plasma ADMA levels were increased in the patient group (p<0.001). After 12 weeks of drug therapy, the patients taking nebivolol had increased levels of plasma NOx , plasma L-arginine, the L-arginine/ADMA ratio and decreased levels of plasma ADMA compared to those of the patients taking metoprolol (p<0.001). In addition, exercise duration to 1-mm ST depression and total exercise duration significantly increased after treatment in the nebivolol group compared to the metoprolol group (p<0.01). In the nebivolol group, Canadian Cardiovascular Society (CCS) angina classification improved by one or more categories in 12 (70%) patients, whereas it deteriorated or remained in the same category in 5 (30%) patients. Meanwhile, in the metoprolol group, the CCS angina classification improved by one or more categories in 7 (41%), whereas it deteriorated or remained in the same category in 10 (59%) patients.
  
  
  CONCLUSIONS
  Circulating endothelial function parameters (plasma ADMA, L-arginine, NOx levels) were impaired in patients with CSX. Nebivolol treatment was associated with better improvements in both circulating endothelial function and exercise stress test parameters than metoprolol. We believe that further studies are needed to evaluate the effects of nebivolol treatment on long-term clinical outcomes in patients with CSX.
authors.affiliation: Department of Cardiology, Faculty of Medicine, Gazi University, Ankara, Turkey. nihatdrsen@yahoo.com
authors.forename: Nihat
authors.initials: N
authors.lastname: Sen
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Tavil
authors.forename: Hüsamettin
authors.initials: H
authors.lastname: Erdamar
authors.forename: Hüseyin Uğur
authors.initials: HU
authors.lastname: Yazici
authors.forename: Erdinç
authors.initials: E
authors.lastname: Cakir
authors.forename: Emin Ozgür
authors.initials: EO
authors.lastname: Akgül
authors.forename: Cumhur
authors.initials: C
authors.lastname: Bilgi
authors.forename: Mehmet Kemal
authors.initials: MK
authors.lastname: Erbil
authors.forename: Fatih
authors.initials: F
authors.lastname: Poyraz
authors.forename: Kaan
authors.initials: K
authors.lastname: Okyay
authors.forename: Murat
authors.initials: M
authors.lastname: Turfan
authors.forename: Mustafa
authors.initials: M
authors.lastname: Cemri
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001578:Benzopyrans / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006328:Cardiac Catheterization; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D004983:Ethanolamines / Q000627:therapeutic use*; D005080:Exercise Test; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008790:Metoprolol / Q000627:therapeutic use; D017566:Microvascular Angina / Q000188:drug therapy*; D000068577:Nebivolol; D009569:Nitric Oxide / Q000097:blood; D016037:Single-Blind Method
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; C487735:dimethylarginine; D000068577:Nebivolol; D009569:Nitric Oxide; D001120:Arginine; D008790:Metoprolol