Published Online
on August 4, 2003

A more recent version of this article appeared on August 12, 2003

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Submitted on March 11, 2003
Revised on May 13, 2003
Accepted on May 14, 2003

Human Cytomegalovirus Seropositivity Is Associated With Impaired Vascular Function

Cairistine Grahame-Clarke PhD, MRCP, Norman N. Chan MRCP, Dawn Andrew; , Geoff L. Ridgway FRCP, FRCPath, D. John Betteridge PhD, MD, Vincent Emery PhD, Helen M. Colhoun MFPHM, and Patrick Vallance MD, FRCP, FMedSci^*

From the Department of Epidemiology and Public Health, University College London, London, UK (N.N.C., H.M.C.); the Department of Virology, Royal Free and University College School of Medicine, Royal Free Campus, London, UK (D.A., V.E.); the Department of Medicine, Royal Free and University College Medical School, London, UK (C.G.-C., D.J.B., P.V.); and the Department of Clinical Microbiology, University College London Hospitals, London, UK (G.L.R.).

^* To whom correspondence should be addressed. E-mail: Patrick.Vallance{at}ucl.ac.uk.

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.

Methods and 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-N^G-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.

Key words: atherosclerosis • risk factors • viruses

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