DALLAS, March 30 -- Antibiotic treatment can reduce the "markers" of inflammation in the circulation of individuals who have coronary heart disease, but it has not yet been shown to prevent heart attacks, according to early results of a study reported today in Circulation: Journal of the American Heart Association.
These findings have led the study's author and principal investigator, Jeffrey L. Anderson, M.D., chief of the division of cardiology at the University of Utah Medical Center in Salt Lake City, and the study's co-principal investigator, J. Brent Muhlestein, M.D., to call for additional research before conclusions are drawn about the relationship between infection and heart disease. Several small earlier investigations indicated a much more dramatic cause-and-effect scenario, but those results may have been "overstated," Anderson says.
"There is a strong reason to believe that inflammation in the blood vessels plays a much larger role in coronary heart disease than was once thought," he adds.
"We now know that such factors as high cholesterol, cigarette smoking, high blood pressure and diabetes can cause inflammation in the blood vessels, which contributes to atherosclerosis, the cause of heart attacks," says Anderson. "If common infectious agents such as Chlamydia pneuomoniae 'rev up' the atherosclerotic inflammatory process, antibiotic therapy could become a major breakthrough treatment against a disease that kills more Americans each year than any other disease.
"We once thought peptic ulcers were unrelated to bacterial infection, but we know today that they can be effectively treated with antibiotics. We need to find out if the same could prove true of heart disease," he continues.
The ongoing two-year trial reported in Circulation includes 302 individuals with established heart disease and evidence of prior infection by a pneumonia-causing organism called Chlamydia pneumoniae. After six months, individuals receiving a three-month course of the antibiotic azithromycin had "modest but significant" reductions in the concentrations of four key markers for blood vessel inflammation, says Anderson.
The inflammatory markers evaluated in the Utah study included C-reactive protein, tumor necrosis factor (TNF) and the interleukins IL-1 and IL-6, molecules secreted by inflammatory cells in the blood vessels and associated with the formation and progression of the fat-laden plaque that characterizes atherosclerosis.
"Lower inflammatory marker levels were evident at six months, but not at three months, which lead researchers to hope that the 'ramping down' of these markers would continue during the 18 remaining months of the study," says Anderson.
"Whether we will see over the full two years a moderate but worthwhile further reduction in the levels of these markers, which are very important signals of inflammation and reduction in the number of cardiovascular events, is unknown," Anderson says.
Thus far, the researchers have found no reduction in the number of heart attacks and other "events" (death; unstable angina, which is chest pain that can not be treated effectively; procedures to restore blood flow such as angioplasty and bypass surgery; or stroke) in the group of individuals receiving azithromycin as compared to those on placebo (an inactive pill). There was also no difference in the quantity of antibodies against Chlamydia observed in the two groups of patients. However, administration of azithromycin substantially reduced the number of infections requiring antibiotics.
"At this point, we don't want to raise wild expectations that heart disease can be cured with a few doses of antibiotics," Muhlestein emphasizes. "Clearly, there are a number of other risk factors involved besides infection, but the established risk factors account for only about half of all cases of heart disease, so we need to keep looking for other answers."
J. Thomas Grayston, M.D., professor of epidemiology at the University of Washington Health Sciences Center in Seattle and author of an editorial published in conjunction with the journal article, agrees that any conclusions based on research completed thus far would be premature.
"Over 20 reports have appeared demonstrating the presence of Chlamydia pneumoniae in atherosclerotic plaques and indicating an association between these organisms and atherosclerosis," Grayston says. "But the evidence we have so far doesn't prove that Chlamydia pneumoniae causes atherosclerosis. Within a few years, the results of two large-scale, long-term studies now going on, each involving several thousand patients, may tell us how important this connection really is."
In the meantime, Grayston adds, the Utah-based trial is contributing valuable information, by showing that the concentrations of well-established inflammation markers may be reduced in patients receiving antibiotic pills and by revealing that earlier studies of antibiotics and heart disease may have overstated the early benefits of antibiotic therapy.
"The important thing is that it's much too early to start treating any heart patients with antibiotics," Grayston says. "The results of large clinical trials now underway will tell whether some of the patients may benefit from antibiotics or if we should lay this whole idea to rest."
Although Chlamydia pneumoniae was not even identified as a separate organism until 1986, it is now known to be the third-leading cause of pneumonia and bronchitis. It is responsible for about 10 percent of all cases of pneumonia, but millions of people also carry it for long periods in a dormant state.
"It is not unreasonable to say that some people carry this organism for the rest of their lives following a respiratory infection," Grayston notes, "and it's amazingly widespread among the general population."
Most American men and women over age 50 have been previously infected with Chlamydia pneumoniae, according to Grayston. "We also found Chlamydia in the plaque, fatty deposits in the blood vessels, of more than 70 percent of our own patients, and that really piqued our interest.
"Laboratory studies have also shown that injections of Chlamydia bacteria can cause rabbits to develop atherosclerosis and the progress of this disease can be delayed by giving the animals antibiotics," says Anderson.
Co-authors are John Carlquist, Ph.D.; Ann Allen, B.S.; Sanjeev Trehan, M.D.; Cindy Nielson, Pharm.D.; Staci Hall; John Brady, B.S., Marlene Egger, Ph.D.; Benjamin Horne B.S.; and Tobin Lim.
Media advisory: Drs. Anderson and Muhlestein can be reached by calling 801-581-7715; (Please do not publish number.)
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