DALLAS, July 15 -- British researchers say they have demonstrated for the first time that signs of a common respiratory infection can be a useful yardstick for predicting whether survivors of heart attack will suffer another attack, which may be fatal, or need treatment to restore blood flow to their hearts. Antibiotic treatment appears to quickly nullify the risk for these heart disease problems, the scientists report in today’s American Heart Association journal Circulation.
The scientists found that patients with the highest blood levels of antibodies to the Chlamydia pneumoniae (Cp) bacterium had a four-times-higher risk of heart disease problems than patients with no detectable Cp antibodies.
Valentin Fuster, M.D., Ph.D., a New York City-based scientist recognized for his own research into possible connections between inflammation and heart disease, says the new study’s results are "quite intriguing." and "reasonably convincing" indications that the micro-organism, which has been detected in blood vessel wall tissues in several recent studies, may be implicated in causing heart attacks.
Fuster, director of the Cardiovascular Institute at Mt. Sinai Medical School and president-elect of the American Heart Association, says that the British study, if validated by further research, may place Cp on a par with cigarette smoking as a lurking "trigger" for heart attack.
The scientists who conducted the study at St. George’s Hospital Medical School in London say their investigation is the first to measure antibodies to the pneumonia-causing microbe in heart attack survivors, then track them over time and document a reduction in heart disease problems (deaths, heart attacks, bypass surgeries, angioplasties and other consequences of heart disease) in those who were treated with the antibiotic azithromycin.
A single, three-day course of antibiotic treatment given to some patients with the highest antibody levels virtually eliminated their increased risk, bringing it down to equal that of a group with no trace of the respiratory germ. There was a similar outcome for patients receiving either a single three-day course of antibiotics or two such courses.
These findings may have important implications for the preventing the onset of coronary heart disease, especially given the safety of azithromycin and the fact that the beneficial effects are observed after only a short course of treatment, according to researcher Sandeep Gupta, M.R.C.P., and colleagues. Larger trials of antibiotics are needed to confirm their findings, the authors add.
The team measured Cp antibodies in the blood of 213 male survivors of heart attacks and divided the patients into three groups, according to antibody levels. The groups were followed for 18 months starting in early 1995, and the incidence of heart disease problems in each group was recorded.
The presence of antibodies only indicates exposure to the bacteria. Gupta and his co-authors say it is not clear whether the elevated antibodies represent "active or past infection."
But such strong new circumstantial evidence that antibody levels predict increased heart disease risk and antibiotics can reduce that risk, leads to intense speculation as to what cellular mechanisms may be involved. Fuster says the process may turn out to be fairly simple.
His laboratory studies have implicated immature white blood cells called monocytes in the formation of blood clots that can ultimately block a disease-narrowed artery, causing a heart attack, he says. Monocytes grow up to be tissue-gobbling scavenger cells called macrophages. Some scientists think the macrophages become infected with microscopic organisms like Chlamydia and, once inside a vessel wall, can cause chronic inflammation that creates excess cell growth leading to blockages.
Fuster, however, speculates that it may be the circulating monocyte itself -- designed by nature to root out blood-borne infection at early stages -- that grabs the offending Chlamydia and takes it through the blood to the site on a vessel wall where fibrous "plaque" already is growing.
The bacteria is thought to turn a monocyte into live "ammunition" for clot formation by stimulating it to produce a clot-promoting substance called tissue factor. After it’s activated, so the theory goes, the monocyte may drift to a patch of plaque on a diseased vessel wall and summon other cells to create a clot on the spot, plugging the vessel and causing a heart attack.
"I am suggesting that the vessel wall that is damaged is very predisposed to blood clots, and as the monocyte circulates with the Chlamydia in it, it is already a pro-coagulant [clot-prone] cell that can very easily become a clot," says Fuster, emphasizing that "this is simply a hypothesis."
Lymphocytes, the predominant infection-fighting white blood cells, aren’t found in large numbers in vessel plaques, he notes, which turned scientific suspicion toward the monocyte.
"If Chlamydia plays a role [in clot formation leading to heart attacks]," Fuster says, "it may be another risk factor, like cigarette smoking." Cigarette smoke, he notes, is also widely believed to stimulate the final step in a heart attack -- i.e., clot formation. Fuster says azithromycin, an antibiotic, thus may become a useful preventive tool for battling heart attacks -- "like discontinuing smoking" already is.
Gupta and his co-workers say it is "reasonable to propose" that azithromycin may have been acting against Cp within the coronary arteries of post-heart attack patients with elevated antibody levels. The authors add that future study should ascertain whether the increased risk they’ve seen also applies to individuals with artery disease who’ve not yet had a heart attack.
Gupta’s co-authors in London include Edward W. Leatham, M.D.; David Carrington, F.R.C.Path; Michael A. Mendall, M.D.; Juan Carlos Kaski, M.D.; and A. John Camm, M.D.
Circulation is one of five journals published in Dallas by the American Heart Association.