Human cytomegalovirus seropositivity is associated with impaired vascular function.
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.
Grahame-Clarke
Cairistine
C
Department of Epidemiology and Public Health, University College London, 5 University St, London, WC1E 6JJ, UK.
Chan
Norman N
NN
Andrew
Dawn
D
Ridgway
Geoff L
GL
Betteridge
D John
DJ
Emery
Vincent
V
Colhoun
Helen M
HM
Vallance
Patrick
P
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*
D000914:Antibodies, Viral; D014665:Vasodilator Agents; D002097:C-Reactive Protein