Emerging concepts in disease management: a role for antimicrobial therapy in coronary artery disease.
Coronary artery disease, the leading cause of morbidity and mortality in developed countries, is a chronic inflammatory process that develops in response to a variety of injuries. A number of microbial organisms have been implicated in its pathogenesis. The strongest evidence to date for an association between an infectious agent and coronary heart disease is that for Chlamydia pneumoniae. Evidence implicating other microbial organisms is much less compelling. Sero-epidemiological and pathological data have linked infection with C. pneumoniae to atherosclerotic coronary artery disease. A possible mechanism by which C. pneumoniae may participate in the pathogenesis of atherosclerosis is through immune activation and the initiation of a chronic inflammatory state in the infected arterial wall. Locally secreted inflammatory cytokines trigger a cascade of secondary cellular processes that lead to characteristic structural changes. C. pneumoniae has been detected in atherosclerotic plaques and in the serum of patients with coronary artery disease. It induces foam cells (the hallmark of early atherosclerosis) and it markedly accelerates this disease process in animal models. C. pneumoniae has been associated with elevated levels of inflammatory cytokines and acute phase reactants. Data from three interventional studies in humans have suggested that treatment with antibiotics decreases inflammatory markers and perhaps influences the anti-C. pneumoniae antibody titers; however, adverse clinical events were not uniformly reduced in all trials. Two large prospective clinical trials, the WIZARD trial and ACES, are underway to confirm these preliminary findings and test the hypothesis that antibiotics may be beneficial in preventing or modifying the course of coronary artery disease. At present, antimicrobial therapy for atherosclerosis is not advocated outside of well-controlled research settings.
Girard
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Mayo Clinic, Infectious Diseases, 200 First St. SW, Rochester, MN 55905, USA.
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000097:blood; D002690:Chlamydia Infections / Q000150:complications* / Q000188:drug therapy; D016993:Chlamydophila pneumoniae; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D011817:Rabbits
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial