The study suggests that antiobiotics might have an anti-inflammatory benefit. The study appears in today's rapid access issue of Circulation: Journal of the American Heart Association.
Researchers were surprised to find that the reduced risk was not related to the presence of two bacteria suspected of playing a role in heart disease - Helicobacter pylori and Chlamydia pneumoniae.
"The beneficial effect of the antibiotics was independent of whether a person was infected with H. pylori or C. pneumonia," says author Michael A. Mendall, M.D., a consultant gastroenterologist at the Mayday Hospital in Croydon, England. "This implies these antibiotics are not working against these organisms. The antibiotics may be acting against other organisms to reduce the overall infectious burden of the body or may have their own anti-inflammatory properties."
The study is the first to compare two different classes of antibiotics in treating acute coronary syndromes. Researchers enrolled 325 patients (225 men and 100 women, ages 39 to 80) hospitalized with a heart attack or unstable angina (severe, unexpected chest pain that occurs at rest). Within 48 hours after being admitted, the patients were randomized to receive amoxycillin, azithromycin, or a placebo for one week. Those in the antibiotic groups also received omeprazole and metronidazole, drugs used in combination with the antibiotics to eradicate H. pylori.
At the start of the study, tests revealed that 157 of 310 patients (51 percent) had antibodies to H. pylori and 132 of 325 patients (41 percent) had antibodies to C. pneumoniae. Blood tests for antibodies detect the dormant bacteria. C. pneumoniae causes one kind of pneumonia and H. pylori causes stomach ulcers.
During one year of follow-up, patients who received the antibiotics were 36 percent less likely to be rehospitalized for unstable angina or a nonfatal heart attack, or to suffer a fatal heart attack, than those who took a placebo.
"It is an interesting proposal that antibiotics can affect a condition that has always been regarded as noninfectious," says Mendall, also a senior lecturer at St. George's Medical School, Tooting, London. "The question, of course, is whether the antibiotics are working against bacteria to improve heart outcome or whether the antibiotics improve outcome by an anti-inflammatory action." Inflammation plays a major role in coronary heart disease. Recent studies suggest that biological markers of inflammation identify people at high risk of developing the disease. Moreover, an association has been shown to exist between chronic infections, inflammatory markers and coronary heart disease.
The researchers, who included both cardiologists and gastroenterologists, set out to explore two issues: First, could the antibiotics amoxycillin, metronidazole and omeprazole (active against H. pylori) and azithromycin, metronidazole and omeprazole (active against C. pneumoniae and H. pylori) reduce levels of C-reactive protein, fibrinogen, and white cells, which at elevated concentrations in the blood indicate inflammation? Second, could the antibiotic treatments reduce the risk of angina and fatal and nonfatal heart attacks?
"The difference between the two antibiotic regimens is that azithromycin is known to have an anti-inflammatory property," Mendall says. "Amoxycillin has not been reported to have an anti-inflammatory effect. Alternately, the failure to find a difference in effect between the two antibiotic regimens suggests that metronidazole or omeprazole may be the important component of the regimen."
Metronidazole is used in other chronic inflammatory conditions such as Crohn's disease, as well as having a different pattern of antibacterial activity to the other antibiotics. Omeprazole has been shown to reduce the activity of macrophages - the key white blood cells involved in coronary heart disease, Mendall explains.
Twelve weeks after beginning the study, 17.2 percent of the patients receiving antibiotics were rehospitalized with unstable angina or a nonfatal heart attack, or suffered a fatal heart attack, compared to 27.2 percent of the placebo group. At the end of one year, the rates were 25.8 percent for those who received antibiotics and 38.9 percent for those who received placebo.
Blood concentrations of the three inflammation markers proved a mixed lot. Amoxycillin takers who had been hospitalized with unstable angina had a significant decline in C-reactive protein over the year-long follow-up compared to the placebo group. However, there was only a trend in those who had suffered a heart attack.
Fibrinogen levels fell in both antibiotic groups compared to patients on placebo, but the change was not statistically significant. No change was found in the levels of white cells.
"Our study design does not allow us to draw conclusions about the beneficial effects in all patients," Mendall says. "Further studies are needed to investigate the reasons for the long-term effects of a short course of antibiotic treatment."
Co-authors are Adam F.M. Stone, M.D.; Juan-Carlos Kaski, M.D., D.Sc.; Tracey M. Edger; Paul Risley; Jan Poloniecki, Ph.D.; A. John Camm, M.D.; and Timothy C. Northfield, M.D.
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