title: Predisposition to atherosclerosis by infections: role of endothelial dysfunction.
abstract: BACKGROUND
  Several microorganisms have been implicated in the pathogenesis of atherosclerosis. We hypothesized that infections may predispose to atherosclerosis by inflicting endothelial injury.
  
  
  RESULTS
  Of 375 patients undergoing coronary angiography, 218 had assessment of endothelial function using intracoronary acetylcholine (ACH) and of endothelium-independent function with sodium nitroprusside and adenosine. Immunoglobulin-G antibody titers to cytomegalovirus, Chlamydia pneumoniae, Helicobacter pylori, hepatitis A virus, and herpes simplex virus-1 were measured. Pathogen burden was defined as the number of positive antibodies. Although positive serology to individual pathogens tended to be associated with increased incidence of coronary arteriosclerosis (CAD), the pathogen burden correlated with the presence of CAD, even after adjustment for risk factors (OR 1.3; 95% CI, 1.05 to 1.6, P=0.018). Moreover, the severity of CAD was independently associated with the pathogen burden (P=0.001). Pathogen burden was an independent predictor of endothelial dysfunction, determined as the percent change in coronary vascular resistance in response to ACH (P=0.009) but not the responses to sodium nitroprusside or adenosine. Pathogen burden was also an independent determinant of endothelial function in the subgroup with angiographically normal coronary arteries.
  
  
  CONCLUSIONS
  The immunoglobulin-G antibody response to multiple pathogens (pathogen burden) is an independent risk factor for endothelial dysfunction and the presence and severity of CAD. Endothelial dysfunction provides the crucial link by which pathogens may contribute to atherogenesis.
authors.affiliation: Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md, USA.
authors.forename: Abhiram
authors.initials: A
authors.lastname: Prasad
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhu
authors.forename: Julian P J
authors.initials: JP
authors.lastname: Halcox
authors.forename: Myron A
authors.initials: MA
authors.lastname: Waclawiw
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology* / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007239:Infections / Q000150:complications* / Q000175:diagnosis / Q000382:microbiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010496:Pericardium / Q000503:physiopathology; D015995:Prevalence; D012307:Risk Factors; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D014665:Vasodilator Agents; D009599:Nitroprusside; D002097:C-Reactive Protein; D000241:Adenosine