Coronary artery disease patients who tested positive for C. pneumoniae showed improved blood flow in the brachial artery (in the arm) and reduced blood levels of two known markers for endothelial dysfunction after five weeks of daily treatment with azithromycin. Patients given placebo did not improve.
Damage to the endothelium, the delicate lining inside arteries and other blood vessels, may lead to atherosclerotic plaques forming and eventually to chest pain (angina) and heart attacks. For several years heart researchers have tried to identify a specific bacterium or virus that might damage the endothelium. Once a microbe was identified, researchers tried to find an antibiotic that could eradicate it, says Juan Carlos Kaski, M.D., a co-author of the study and a professor of cardiovascular science at St. George’s Hospital Medical School, London. He says that C. pneumoniae proved to be a good candidate for this approach because it is a common infection and evidence of it has been discovered in plaque removed from arteries of people with coronary artery disease.
“We have found in this study that treatment with azithromycin, an antibiotic used to treat C. pneumoniae infections, improved the function of the endothelium,” says Kaski. “The antibiotic thus appears to allow the artery to increase its caliber.” This caliber change means the vessel widens in response to appropriate stimuli. Forty males, average age 55, were enrolled in the study. All had documented coronary artery disease. They were randomly assigned to receive either azithromycin or placebo for five weeks. Flow-mediated dilation (FMD) of the brachial artery was measured at study entry and at the end of treatment. FMD measures the blood vessel’s ability to relax in response to blood flow increases, and also endothelial function. A healthy artery (with a healthy endothelium) will be more “flexible” than a diseased artery. In addition, levels of E-selectin and von Willebrand factor (both markers of endothelial dysfunction) and levels of C-reactive protein (a marker of inflammation) were measured at entry and after treatment.
After treatment, patients’ average FMD of the brachial artery improved from 2.66 percent at baseline to 4.78 percent. In the placebo group the baseline measurement was 3.11 percent and at five weeks it was 3.09 percent, indicating no improvement. Moreover, in treated patients, the level of E-selectin declined by an average of 28.2 nanograms per milliliter (ng/mL) in treated patients and von Willebrand factor level declined by an average of 36.6 International Units per deciliter (IU/dL).
The study showed improved arterial function, but it was not designed to provide evidence that the antibiotic could reverse atherosclerosis or reduce the number of heart attacks. Moreover, Kaski says the benefit of the antibiotic might not be a direct result of the drug’s ability to eradicate the pathogen, because their study showed that patients who had very high levels of C. pneumoniae antibodies had essentially the same benefit as those with low levels.
A direct anti-inflammatory action of the antibiotic has been suggested because azithromycin is in a class of drugs called macrolides, which have anti-inflammatory effects. Inflammation is one of the body’s responses to infection. But Kaski says that the question remains open since azithromycin did not reduce the levels of C-reactive protein in this study.
“Thus whether the beneficial effects of azithromycin were due to its antibacterial or anti-inflammatory actions is unresolved by our study,” says Kaski.
The next step, he says, is to design a study that will allow the researchers to “identify the mechanism responsible for the beneficial effect of antibiotics so that we arrive at a rational treatment, which might include developing even more effective antibiotics or perhaps a vaccine, or just appropriate anti-inflammatory agents.” However, it is too soon to recommend the use of antibiotics to either treat or prevent heart disease.
Kaski’s co-authors were Nikhil Parchure, MRCP, and Emmanouil G. Zouridakis, M.D.
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