title: Impact of infectious burden on extent and long-term prognosis of atherosclerosis.
abstract: BACKGROUND
  Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. In hypothesizing an association between infectious agents and the development of atherosclerosis, we would expect a correlation to the extent of atherosclerosis. Moreover, this effect could be multiplied by the number of pathogens to which an individual had been exposed.
  
  
  RESULTS
  In 572 patients, IgG or IgA antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, Hemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were measured. The extent of atherosclerosis was determined by coronary angiography, carotid duplex sonography, and evaluation of the ankle-arm index. Elevated IgA antibodies against C pneumoniae (P<0.04) and IgG antibodies against H pylori (P<0.02), cytomegalovirus (P<0.05), and herpes simplex virus 2 (P<0.01) were associated with advanced atherosclerosis (> or =2 vascular regions), adjusted for age, sex, cardiovascular risk factors, and highly sensitive C-reactive protein. Infectious burden divided into 0 to 3, 4 to 5, and 6 to 8 seropositivities was significantly associated with advanced atherosclerosis, with an odds ratio (95% CI) of 1.8 (1.2 to 2.6) for 4 to 5 (P<0.01) and 2.5 (1.2 to 5.1) for 6 to 8 seropositivities (P<0.02) (adjusted). After a mean follow-up of 3.2 years, cardiovascular mortality rate was 7.0% in patients with advanced atherosclerosis and seropositive for 0 to 3 pathogens compared with 20.0% in those seropositive for 6 to 8 pathogens.
  
  
  CONCLUSIONS
  Our results support the hypothesis that infectious agents are involved in the development of atherosclerosis. We showed a significant association between infectious burden and the extent of atherosclerosis. Moreover, the risk for future death was increased by the number of infectious pathogens, especially in patients with advanced atherosclerosis.
authors.affiliation: Department of Medicine II, Johannes Gutenberg University Mainz, Germany. espinola@mail.uni-mainz.de
authors.forename: Christine
authors.initials: C
authors.lastname: Espinola-Klein
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Rupprecht
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: Christoph
authors.initials: C
authors.lastname: Bickel
authors.forename: Helmuth
authors.initials: H
authors.lastname: Kopp
authors.forename: Gerd
authors.initials: G
authors.lastname: Rippin
authors.forename: Anja
authors.initials: A
authors.lastname: Victor
authors.forename: Gerd
authors.initials: G
authors.lastname: Hafner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlumberger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Meyer
mesh_terms: D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism / Q000401:mortality; D001424:Bacterial Infections / Q000097:blood / Q000150:complications* / Q000382:microbiology; D002097:C-Reactive Protein / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D004266:DNA Virus Infections / Q000097:blood / Q000150:complications* / Q000821:virology; D005260:Female; D006193:Haemophilus influenzae / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009177:Mycoplasma pneumoniae / Q000276:immunology; D011379:Prognosis; D012307:Risk Factors; D018139:Simplexvirus / Q000276:immunology; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D014780:Viruses
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D002097:C-Reactive Protein