title: Human cytomegalovirus seropositivity is associated with impaired vascular function.
abstract: BACKGROUND
  Herpesvirus infection is a possible risk factor for atherogenesis, and diabetics may be at particular risk. Endothelial dysfunction is an early marker for atherosclerosis, and the present study tests the hypotheses that (1) prior infection with cytomegalovirus (CMV) and herpes simplex virus (HSV) is associated with endothelial dysfunction and (2) this may be more marked in diabetics.
  
  
  RESULTS
  Serum samples were tested for anti-IgG antibodies to CMV and HSV from 400 subjects (mean age for diabetics and nondiabetics, 37.8+/-4.3 and 37.9+/-3.7 [SD]). We also assessed Helicobacter pylori and Chlamydia pneumoniae serology. Coronary atheroma was quantified by means of electron beam computed tomography. Subjects (n=157) underwent venous occlusion plethysmography with acetylcholine, bradykinin, glyceryl trinitrate, norepinephrine, and l-NG-monomethyl-l-arginine. Individuals who were seropositive for CMV had reduced responses to bradykinin (P=0.005) and glyceryl trinitrate (P=0.006). The reduced response to bradykinin remained significant (P=0.045) after adjusting for the response to glyceryl trinitrate and was independent of conventional risk factors. Positive serology for the other organisms did not have an independent effect on reactivity. There was a weaker association between CMV and coronary artery calcification (P=0.09). Positive serology for each of the other pathogens did not affect reactivity, but there was a relation between total pathogen burden and impaired vascular reactivity. No significant differences were found between diabetics and nondiabetics.
  
  
  CONCLUSIONS
  This study shows that CMV-seropositive individuals have endothelial dysfunction and impaired responses to NO. This association was independent of conventional risk factors and may be associated with increased atherosclerosis burden.
authors.affiliation: Department of Epidemiology and Public Health, University College London, 5 University St, London, WC1E 6JJ, UK.
authors.forename: Cairistine
authors.initials: C
authors.lastname: Grahame-Clarke
authors.forename: Norman N
authors.initials: NN
authors.lastname: Chan
authors.forename: Dawn
authors.initials: D
authors.lastname: Andrew
authors.forename: Geoff L
authors.initials: GL
authors.lastname: Ridgway
authors.forename: D John
authors.initials: DJ
authors.lastname: Betteridge
authors.forename: Vincent
authors.initials: V
authors.lastname: Emery
authors.forename: Helen M
authors.initials: HM
authors.lastname: Colhoun
authors.forename: Patrick
authors.initials: P
authors.lastname: Vallance
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D019540:Area Under Curve; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000032:analysis; D023521:Chlamydophila Infections / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D015331:Cohort Studies; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000453:epidemiology; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology*; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D016481:Helicobacter Infections / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D006561:Herpes Simplex / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012039:Regional Blood Flow; D016036:Seroepidemiologic Studies; D017678:Sex Distribution; D012923:Social Class; D006113:United Kingdom / Q000453:epidemiology; D014665:Vasodilator Agents; D014666:Vasomotor System / Q000503:physiopathology*
chemical_list: D000914:Antibodies, Viral; D014665:Vasodilator Agents; D002097:C-Reactive Protein