title: Effects of smoking on coronary microcirculatory function: a twin study.
abstract: BACKGROUND
  In asymptomatic smokers, coronary microcirculatory dysfunction, assessed by coronary flow reserve (CFR), is an early indicator of cardiovascular risk. Inflammation and oxidative stress may be the mechanisms through which smoking affects the microvasculature.
  
  
  OBJECTIVE
  The purpose of this study was to determine the relationship between smoking and CFR, taking into account potential shared genetic effects.
  
  
  METHODS
  We examined 360 male middle aged twins (288 non-smokers and 72 smokers), including 46 twin pairs discordant for current smoking. Coronary flow reserve (CFR) in response to adenosine was measured with positron emission tomography [N(13)] ammonia and quantitation of coronary blood flow at rest and after adenosine stress. Inflammation was assessed by measuring interleukin-6 and C-reactive protein, and oxidative stress was determined by measuring plasma hydroperoxides, glutathione (GSH), the oxidized form of GSH, GSSG, and the ratio of GSH to GSSG.
  
  
  RESULTS
  CFR was significantly lower in smokers compared to nonsmokers (2.25 vs. 2.75, p<0.01). This relationship persisted after accounting for known cardiovascular disease risk factors, and was marginally affected by adjusting for inflammatory and oxidative stress biomarkers. In addition, in smoking-discordant twin pairs, CFR in the smoking twin was significantly lower than in the non-smoking co-twin (2.25 vs. 2.67, p=0.03) even after adjustment for cardiovascular risk factors.
  
  
  CONCLUSIONS
  Our results demonstrate the adverse effects of smoking in the early phases of cardiovascular disease. Mechanisms other than peripherally measured inflammation and oxidative stress are involved.
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Cherie
authors.initials: C
authors.lastname: Rooks
authors.forename: Tracy
authors.initials: T
authors.lastname: Faber
authors.forename: John
authors.initials: J
authors.lastname: Votaw
authors.forename: Emir
authors.initials: E
authors.lastname: Veledar
authors.forename: Jack
authors.initials: J
authors.lastname: Goldberg
authors.forename: Paolo
authors.initials: P
authors.lastname: Raggi
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.forename: J Douglas
authors.initials: JD
authors.lastname: Bremner
authors.forename: Viola
authors.initials: V
authors.lastname: Vaccarino
mesh_terms: D002318:Cardiovascular Diseases / Q000175:diagnosis; D003326:Coronary Circulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D012306:Risk; D012907:Smoking / Q000009:adverse effects*