Role for chronic infections in atherosclerosis?

To the Editor: The study by Espinola-Klein et al1 showed a significant association between infectious burden (C pneumoniae, H pylori, cytomegalovirus, herpes simplex virus 2) 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. The specific IgG or IgA antibodies used in the study, however, do not necessarily distinguish between persistence of infections and only a previous contact. Other more sensitive markers of actual infections are available: specific IgG-containing immune complexes for C pneumoniae2; the C-urea breath test for H pylori3; specific polymerase chain reaction for cytomegalovirus and herpes simplex virus 2 infections.4 Because of these limitations, the present data do not really indicate that these infectious agents per se play a direct role in atherosclerosis. On the other hand, the high prevalence of a seropositivity to multiple infectious agents in atherosclerotic patients may rather suggest a “bystander activation” of the immune system.5 Autoreactive T cells may exist in these subjects, representing a potential reservoir of pathogenic effectors that, when stimulated by microbial adjuvants, could trigger an autoimmune phenomenon. The induction of cross-reactivity does not require a replicating agent, and immune-mediated injury can occur after the immunogen has been removed. In our opinion, this mechanism could better explain the significant association found among seropositivity to multiple different infectious agents, extension of atherosclerosis, and long-term prognosis of atherosclerotic patients.