Is Antibiotic Treatment Effective for Coronary Artery Disease?

Within the last 15 years there has been considerable discussion concerning the multiple contributors to coronary artery disease. With the realization during the late 1990s that atherosclerosis is an inflammatory response, attention has been directed to the possible role of infection. Early research into the role of Chlamydia pneumoniae generated interest in pursuing clinical trials using antibiotics to mitigate the effects of C pneumoniae and other organisms. Early trials were promising, with reduction in adverse events within months of the initiation of antibiotics and documentation of long-term benefits. However, there were inconsistencies within these small, early trials. Thereafter, larger multicenter trials were conducted but none were able to document long-term benefit. At most, a benefit was shown during the first 6 months of therapy. Since the conThe Journal of Applied Research • Vol. 7, No. 1, 2007 39 Vol. 7, No. 1, 2007 • The Journal of Applied Research 40 ing by microorganisms such as Chlamydia pneumoniae. Studies in the late 1990s first began augmenting current treatment for myocardial infarction (MI) and acute coronary syndrome (ACS) with antibiotics. These studies were small but had promising results.2 On a parallel track, research began on other organisms, such as Helicobacter pylori, herpes simplex virus, cytomegalovirus,3 and, most recently, nanobacteria.4 There may be other organisms involved in the initiation of atherosclerotic disease since improvement due to antibiotic treatment was often noted even with negative immunoassay for the proposed organisms. Over the last 6 years, several studies have reported conflicting results on antibiotic treatment of patients with demonstrated arteriosclerosis or confirmed cardiac disease. This review compares and critiques these studies and discusses treatment options and future recommendations. METHODS A review of current literature was conducted using Internet search engines such as PubMed and Medline using the keywords “antibiotic,” “coronary heart disease,” “atherosclerosis,” “inflammation,” “thrombosis,” “clinical trials,” “prospective trials,” “Chlamydia pneumoniae,” “Helicobacter pylori,” and “nanobacteria.” Data from several clinical trials were reviewed for statistical significance and results were compared. The choice of antibiotic, timing of delivery of medication, follow-up period, lab results, and endpoints were gathered and presented. RESULTS Current Evidence for the Role of Infection The most well-researched pathogen in recent studies of coronary artery disease is C pneumoniae. These intracellular bacteria can be rather difficult to eradicate with short courses of antibiotics. It is estimated that 50% of the adult population has been exposed to C pneumoniae, as evidenced by immunoassay.5 C pneumoniae or its cellular components have been demonstrated in postmortem examinations of plaques found in cardiac and carotid arteries. In fact, of 50 studies conducted prior to 2000, all but 4 documented the pathogen within atherosclerotic tissue.6 C pneumoniae has been shown in vivo to be sensitive to macrolides, tetracyclines, and fluoroquinolones. Most commonly, azithromycin (Zithromax; Pfizer, New York, NY) is the drug of choice.7,8 A second organism proposed to have an impact on atherosclerosis is Helicobacter pylori, via seeding of the vasculature.9 The invasive nature of this bacteria, coupled with its ability to cause gastric ulcer, led to investigations of its vascular impact. Nanobacteria were first discovered in hot springs in the early 1990s but were not researched until the late 1990s. These bacteria are still controversial in that they are significantly smaller than any known bacteria, and some theorize that they are too small to act as bacteria as we understand it. However, these organisms have been shown to form calcific shells and biofilms. Researchers have demonstrated nanobacteria in calcified arterial plaques.4,10 Nanobacteria have also been found in renal calculi, billary stones, and other areas of abnormal calcification in vivo. Although treatment trials are just beginning, anecdotal evidence implies that this may be a major cause of arterial calcification that is easily treated.11 Both herpes simplex virus and cytomegalovirus have been demonstrated in vitro to cause endothelial damage.12 They may also cause a generalized immune response promoting a worsening of chronically inflamed arterial