title: The impact of third-generation beta-blocker antihypertensive treatment on endothelial function and the prothrombotic state: effects of smoking.
abstract: BACKGROUND
  The significance of beta-blockers in the treatment of cardiovascular diseases is well established. The effect of vasodilating beta-blockers on endothelial function and prothrombotic state has not been investigated.
  
  
  METHODS
  The study comprised 550 consecutive patients with uncomplicated essential hypertension. They were treated with celiprolol, carvedilol or nebivolol monotherapy (171, 179, and 200 patients, respectively), achieving comparable blood pressure reduction. Plasma levels of fibrinogen and homocystine and serum levels of plasminogen activator inhibitor-1 (PAI-1) were obtained before and 6 months after initiation of treatment.
  
  
  RESULTS
  The three drugs differentiated in regard to homocystine (P <.00001) and fibrinogen level changes (P =.00003), but not (P = NS) in PAI-1 change. In smokers, differentiation was found in all three parameters (P =.0002, P =.001, and P =.006 for fibrinogen, PAI-1, and homocystine, respectively), but in nonsmokers differentiation was found only in homocystine change (P =.00003). In smokers, fibrinogen, PAI-1, and homocystine were reduced more (P =.002, P =.0009, and P <.0001, respectively) than in nonsmokers in the whole study cohort. The effect of nebivolol was more prominent in smokers than nonsmokers in reducing all three parameters (P =.0001,.003, and.003, respectively), whereas in celiprolol and carvedilol-treated groups, differentiation between smokers and nonsmokers was significant (P =.00003 and.01, respectively) only in homocystine level change.
  
  
  CONCLUSIONS
  In hypertensive smokers, nebivolol resulted in a significant decrease of plasma PAI-1, fibrinogen and homocystine. Celiprolol also significantly affected these parameters but to a lesser degree, whereas carvedilol had no significant favorable action. In nonsmokers, homocystine was reduced significantly by nebivolol. We conclude that smoking status should be a determinant of antihypertensive treatment choice.
authors.affiliation: First Cardiology Department of Athens University, Hippokration Hospital, Athens, Greece.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Vyssoulis
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Marinakis
authors.forename: Konstantinos A
authors.initials: KA
authors.lastname: Aznaouridis
authors.forename: Eva A
authors.initials: EA
authors.lastname: Karpanou
authors.forename: Athina N
authors.initials: AN
authors.lastname: Arapogianni
authors.forename: Dennis V
authors.initials: DV
authors.lastname: Cokkinos
authors.forename: Christodoulos I
authors.initials: CI
authors.lastname: Stefanadis
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001578:Benzopyrans / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000627:therapeutic use; D000077261:Carvedilol; D017272:Celiprolol / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D004983:Ethanolamines / Q000627:therapeutic use; D005260:Female; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D006711:Homocystine / Q000097:blood / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011412:Propanolamines / Q000627:therapeutic use; D012907:Smoking / Q000097:blood; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001578:Benzopyrans; D015415:Biomarkers; D002227:Carbazoles; D004983:Ethanolamines; D017395:Plasminogen Activator Inhibitor 1; D011412:Propanolamines; D000068577:Nebivolol; D000077261:Carvedilol; D006711:Homocystine; D005340:Fibrinogen; D017272:Celiprolol