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(Circulation. 2003;107:1966.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Absence of Association Between Infectious Agents and Endothelial Function in Healthy Young Men

Paul Khairy, MD, MSc; Stéphane Rinfret, MD, MSc; Jean-Claude Tardif, MD; Richard Marchand, MD; Stan Shapiro, PhD; James Brophy, MD, PhD; Jocelyn Dupuis, MD, PhD

From the Department of Medicine (P.K., S.R., J.-C.T., R.M., J.D.), Montreal Heart Institute, University of Montreal, and Department of Epidemiology and Biostatistics (P.K., S.S., J.B.), McGill University, Montreal, Quebec, Canada.

Correspondence to Jocelyn Dupuis, MD, PhD, Research Center, Montreal Heart Institute, 5000 Belanger St East, Montreal, Quebec, Canada H1T 1C8. E-mail dupuisj{at}icm.umontreal.ca

Background— Although several studies have reported correlations between infections and coronary artery disease, associations with endothelial dysfunction, its precursor, have not been established. This study assessed whether infection with Chlamydia pneumoniae (CP), cytomegalovirus (CMV), Epstein-Barr virus (EBV), or Helicobacter pylori (HP) is associated with decreased endothelial function.

Methods and Results— Sixty-five male subjects, aged 20 to 45 years, with no risk factors or known coronary artery disease were enrolled in a seroepidemiological cross-sectional study. Endothelial function was determined by flow-mediated brachial vasodilation. Serum antibodies consisting of anti-CP IgG and IgM, anti-CMV IgG, anti-EBV nuclear antigen, and anti-HP IgG and markers of inflammation including high-sensitivity C-reactive protein were measured. Average age was 29.3±5.5 years. Seroprevalence values were 65.1%, 34.9%, 88.9%, and 14.3% for CP, CMV, EBV, and HP, respectively. Average values for endothelium-dependent and -independent vasodilation were 9.4±4.5% and 12.6±5.0%. Despite adequate statistical power (82% for the primary end point), no association between endothelial function and seropositivity to individual infectious agents, infectious burden, or C-reactive protein was observed in regression analyses controlling for variables including age, blood pressure, and lipid parameters. Moreover, no dose-response trends between serum titers and endothelial function were found.

Conclusions— Lack of association between chronic infection with CP, CMV, EBV, HP, or pathogen burden and endothelial function was observed, suggesting that these agents are not implicated as early etiologic triggers in the genesis of coronary artery disease. These results do not preclude active involvement at later stages of the pathophysiological process, such as acceleration of existing atherosclerosis and acute plaque rupture.

Key Words: endothelium • vasodilation • infection

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