title: Endothelial Dysfunction is Associated with Occult Coronary Artery Disease Detected by Positron Emission Tomography.
abstract: OBJECTIVE
  Silent myocardial ischemia is common in asymptomatic subjects without a prior history of coronary artery disease (CAD) and is associated with increased morbidity and mortality. Our objective was to determine whether endothelial dysfunction is associated with silent myocardial ischemia and whether the association is independent of genetic and familial factors.
  
  
  METHODS
  We examined 416 male monozygotic and dizygotic twins aged 47 to 63 years, free of symptomatic CAD. Subclinical ischemia was diagnosed by [13N] ammonia positron emission tomography at rest and after adenosine stress. Endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery. Generalized estimating equations were used for analysis.
  
  
  RESULTS
  Fixed perfusion defects were found in 24 (6%) twins and reversible perfusion defects in 90 (22%) twins, indicating subclinical ischemia. There was an inverse correlation between FMD and the reversible perfusion defect score (r = - 0.14, p=0.01) but not the fixed defect score (r= -0.017, p=0.73). From the lowest to the highest quartile of FMD, the prevalence of reversible defects decreased 28% to 14%, p=0.008. In multivariable analysis, reversible defects were significantly associated with each quartile of decreasing FMD (OR =1.3; 95% 1.1, 2.5). In 54 twin pairs discordant for endothelial dysfunction (FMD ≤ 7% dilation from baseline), twins with endothelial dysfunction had 9% higher likelihood of having perfusion defects than their co-twins without endothelial dysfunction (p=0.041).
  
  
  CONCLUSIONS
  Endothelial dysfunction is independently associated with silent ischemia and this association is not confounded by genetic or other shared familial factors.
authors.affiliation: Department of Epidemiology, Emory University School of Public Health, Atlanta, GA ; Division of Cardiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Ambar
authors.initials: A
authors.lastname: Kulshreshtha
authors.affiliation: Department of Epidemiology, Emory University School of Public Health, Atlanta, GA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Division of Cardiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.affiliation: Department of Epidemiology, Emory University School of Public Health, Atlanta, GA ; Division of Cardiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Emir
authors.initials: E
authors.lastname: Veledar
authors.affiliation: Department of Radiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: John
authors.initials: J
authors.lastname: Votaw
authors.affiliation: Department of Radiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Irina
authors.initials: I
authors.lastname: Uphoff
authors.affiliation: Department of Psychiatry, Emory University School of Medicine, Atlanta, GA.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Bremner
authors.affiliation: Vietnam Era Twin Registry, Seattle, WA ; University of Washington School of Public Health, Seattle, WA.
authors.forename: Jack
authors.initials: J
authors.lastname: Goldberg
authors.affiliation: Department of Epidemiology, Emory University School of Public Health, Atlanta, GA ; Division of Cardiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Viola
authors.initials: V
authors.lastname: Vaccarino
keywords: Endothelial dysfunction; Flow-mediated vasodilation; Positron Emission Tomography; Silent ischemia