The Role of Infection in Carotid Plaque Pathogenesis and Stability: The Clinical Evidence

Gregory      C. Makris; Marinos      C. Makris; Victoria      V. Wilmot; George      Geroulakos; Matthew      E. Falagas

Abstract

Introduction: Chlamydia pneumoniae was the first pathogen linked with carotid atherosclerotic changes and plaque rupture. Currently, other common pathogens are also under investigation as potential contributors. Methods: A systematic review of PubMed and Scopus databases was performed. Studies evaluating the infectious burden between symptomatic and asymptomatic patients with carotid plaque disease (CPD) were included. Furthermore, trials referring to common infectious agents (other than C. pneumoniae) incriminated for contribution in CPD were analyzed separately. Results: Forty four studies were identified; 6 investigated the connection of infection with the plaque destabilization, 3 of which reported a significant association between infection and symptoms. Studies retrieved for the investigation of agents other than C. pneumoniae were: 18 about viruses, 16 about other bacteria and 4 examining both. Significant association or high detection rates of agents’ genome or specific antibodies with CPD characteristics (intima media thickness values > 1mm or symptoms) were found in a number of studies: 3 for HCV, 2 for CMV and 1 for enterovirus, EBV, HBV, and HIV. Moreover 4 studies about dental pathogens (i.e. Porpyromonas gingivalis), 5 about H. Pylori strains and 1 about Borrelia burgdorferi were identified supporting a positive association. Conclusion: There is considerable evidence supporting the contribution of other commonly encountered pathogens in the pathogenesis and rupture of the carotid plaque. Research in this direction should not be abandoned and further studies are necessary to elucidate the exact role of common infections in the pathogenesis and development of CPD and how this can be translated into novel pharmacological approaches for prevention and treatment.

Keywords: Carotid plaque, infection, antibiotics, antivirals, Chlamydia pneumoniae, carotid atherosclerotic changes, carotid plaque disease, HCV, CMV, enterovirus, EBV, HBV, HIV, Porpyromonas gingivalis, H. Pylori, Borrelia burgdorferi, Atherosclerosis, anti-chlamydial agents, coronary artery dis-ease, Helicobacter pylori, herpes simplex virus, cytomegalovirus, carotid endarterectomy, polymerase chain reaction, tumor necrosis factor, atherosclerotic plaques, hepatitis C, hepatitis B, intima media thickness, antiretroviral therapy, periodontitis, Por-phyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia, Prevotella intermedia, Actinobacillus actinomycetemcomitans, Mycobacterium Tuberculosis, Diphtheroid, Staphylococcus Species, CD8 positive cytotoxic T cells, CD4 positive T cells, azithromycin, clarythromycin, roxyth-romycin