title: The role of plasma aminothiols in the prediction of coronary microvascular dysfunction and plaque vulnerability.
abstract: BACKGROUND
  Although oxidative stress is considered a key pathogenic step in mediating vascular dysfunction and atherosclerosis development, their association has not been evaluated in human coronary circulation in vivo. Accordingly, we hypothesized that higher oxidative stress would be associated with abnormal coronary epicardial structure and microvascular function.
  
  
  METHODS
  We measured coronary flow velocity reserve (CFVR) and hyperemic microvascular resistance (HMR) as indices of microvascular function, and epicardial plaque volume and necrotic core using intravascular ultrasound (IVUS) in 47 patients undergoing cardiac catheterization. Plasma glutathione, cystine and their ratio served as measures of oxidative stress while high-sensitivity C-reactive protein (hs-CRP) served as a measure of inflammation.
  
  
  RESULTS
  Lower glutathione, a measure of increased oxidative stress was associated with impaired microvascular function [CFVR (r=0.39, p=0.01) and HMR (r=-0.43, p=0.004)], greater plaque burden (r=-0.32, p=0.03) and necrotic core (r=-0.39, p=0.008). Similarly, higher cystine/glutathione ratio was associated with impaired microvascular function [CFVR (r=-0.29, p=0.04)] and greater necrotic core (r=0.37, p=0.01). In comparison, higher hs-CRP was associated only with greater necrotic core (r=0.45, p=0.003). After multivariate adjustment for age, gender, hypertension, diabetes, acute coronary syndrome presentation, body mass index, tobacco abuse, statin use and hs-CRP, glutathione remained an independent predictor of CFVR, HMR and necrotic core (p<0.05).
  
  
  CONCLUSIONS
  Lower plasma glutathione level a measure of increased oxidative stress, was an independent predictor of impaired coronary microvascular function and plaque necrotic core.
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States.
authors.forename: Saurabh S
authors.initials: SS
authors.lastname: Dhawan
authors.forename: Parham
authors.initials: P
authors.lastname: Eshtehardi
authors.forename: Michael C
authors.initials: MC
authors.lastname: McDaniel
authors.forename: Lucy V
authors.initials: LV
authors.lastname: Fike
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.forename: Habib
authors.initials: H
authors.lastname: Samady
mesh_terms: D000368:Aged; D001783:Blood Flow Velocity; D002097:C-Reactive Protein / Q000378:metabolism; D006328:Cardiac Catheterization; D003324:Coronary Artery Disease / Q000503:physiopathology; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D003545:Cysteine / Q000097:blood*; D003553:Cystine / Q000097:blood; D005260:Female; D005978:Glutathione / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D010496:Pericardium / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D012307:Risk Factors; D014463:Ultrasonography
chemical_list: D003553:Cystine; D002097:C-Reactive Protein; D005978:Glutathione; D003545:Cysteine