title: Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease.
abstract: OBJECTIVE
  We assessed the hypothesis that changes in endothelial vasomotor function in response to optimized therapy for atherosclerotic coronary artery disease predict future cardiovascular events.
  
  
  BACKGROUND
  Although endothelial vasomotor dysfunction is a predictor of cardiovascular events, it remains unclear whether reversibility of endothelial dysfunction in response to risk factor reduction provides prognostic information.
  
  
  METHODS
  This study included 251 patients with newly diagnosed coronary artery disease and an impaired flow-mediated dilation (FMD) of the brachial artery (FMD <5.5%). Measurement of FMD was repeated after 6 months for individualized and optimized therapy to reduce risk factors according to American College of Cardiology/American Heart Association guidelines. Patients were followed up for 36 months or until 1 of the following events occurred: cardiac death, nonfatal myocardial infarction, recurrent and refractory angina pectoris requiring coronary revascularization, or ischemic stroke.
  
  
  RESULTS
  FMD was persistently impaired (<5.5%) in 104 (41%) patients after 6 months of optimized therapy, whereas it improved (FMD > or =5.5%) in the remaining 147 (59%) patients. During 36 months of follow-up, events occurred in 27 (26%) patients with persistently impaired FMD and in 15 (10%) patients with improved FMD (p < 0.01 by chi-square test). Multivariate Cox hazards analysis showed that persistent impairment of FMD was an independent predictor of events (hazard ratio: 2.9, 95% confidence interval: 1.5 to 6.2, p < 0.01). Baseline FMD before the optimized therapy to reduce risk factor had no significant prognostic information.
  
  
  CONCLUSIONS
  Persistent impairment of endothelial vasomotor function despite optimized therapy to reduce risk factors has an adverse impact on outcome in coronary artery disease patients.
authors.affiliation: Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine, Yamanashi, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kitta
authors.forename: Jyun-ei
authors.initials: JE
authors.lastname: Obata
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Hirano
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kodama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujioka
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saito
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Keita
authors.initials: K
authors.lastname: Sano
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yano
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kugiyama
mesh_terms: D000368:Aged; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003324:Coronary Artery Disease / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D016896:Treatment Outcome; D014463:Ultrasonography