Study Links Heart Disease to Bacterial Infections

Researchers say they have for the first time demonstrated a direct link between bacterial infection and heart disease, confirming a suspicion that has been floating through the cardiology community for the better part of a decade.

The proof of a link suggests that at least some of the 961,000 deaths from heart disease in the United States every year could be prevented by treatment with antibiotics or, even better, by immunization against the responsible organisms.

It also might lead to new ways to identify people at the highest risk of death, experts said.

In the study, reported today in the journal Science, researchers from the Ontario Cancer Institute in Toronto, Canada, found that injecting mice with proteins from chlamydia bacteria can produce heart disease. As many as 95% of people are exposed to chlamydia during their lives.

The chlamydia protein, which sits on the bacterium’s surface, is virtually identical to one found in healthy heart tissue. When the mouse’s immune system gears up to attack the protein, it also damages the heart and coronary arteries.

“Ours is the first experimental proof to show how bacterial infection . . . can lead to heart disease,” said Dr. Josef M. Penninger of the Ontario Cancer Institute. “The results nearly knocked me off my chair.”

The results do not mean that high cholesterol, smoking, obesity and hypertension are not important factors in heart disease, said Dr. Paul Ridker of Harvard Medical School. Rather, the findings add one more risk factor to the constellation of health problems that lead to heart attacks.

Antibiotic Trials Backed

Though Ridker and some others do not believe that the case against chlamydia has been conclusively proved, they support human trials to see if antibiotics can prevent some heart attacks. “The public health importance is large enough that well-designed clinical trials [of antibiotic therapy] are worth the effort,” he said.

Already, three large trials enrolling more than 8,000 heart disease patients are underway to determine if antibiotics effective against chlamydia reduce the risk of heart attacks.

One of those trials is directed by Dr. P.K. Shah of Cedars-Sinai Medical Center in Los Angeles. He believes the new results “may be enough to tip the balance” of evidence toward the idea that bacteria cause heart disease.

But, he added, “the proof is still going to be in the pudding. We won’t be sure until we see the results of the clinical trials.”

The idea that infection can cause heart disease is not new. The streptococci bacteria that cause rheumatic fever also attack the heart, causing lingering damage. Several viruses attack the heart directly, producing myocarditis, which is often fatal.

Staphylococcal and streptococchal bacteria also have been shown to cause Kawasaki syndrome, a disorder in children that is marked by severe heart disease.

But those conditions are rare. Now some scientists are beginning to believe that infections may play a role in the vast majority of heart disease patients, perhaps as many as 80% of the nearly 14 million Americans who have coronary heart disease. But pinning down those links has proved elusive.

There have been many findings hinting at such a link. As many as 20% of heart attack victims do not have any of the known risk factors for heart disease, said Dr. Marvin I. Dunn of the University of Kansas School of Medicine in Kansas City.

Moreover, blocked coronary arteries show strong evidence of inflammation--an accumulation of white blood cells resulting from an immune attack on an infectious agent.

Ridker has shown that the risk of heart attack can be predicted by measuring the levels of so-called C-reactive protein, which is also produced in the inflammatory process caused by infections.

Many infectious agents have been tentatively linked to heart disease. Among them are: bacteria from the mouth, which can cause blood to clot; cytomegalovirus, a herpes virus that causes blindness, and Helicobacter pylori, which causes ulcers.

But much of the focus has recently shifted to Chlamydia pneumoniae and its close relatives, C. psittaci and C. trachomatis.

First identified in 1986 by Dr. J. Thomas Grayston of the University of Washington School of Public Health, C. pneumoniae causes at least 10% of all cases of pneumonia. C. psittaci causes psittacosis, or parrot fever, an influenza-like disease transmitted by birds. C. trachomatis is a common sexually transmitted disease and is a major cause of female infertility.

Since the discovery of C. pneumoniae, several studies have shown that it is present in a high percentage of clogged arteries, but rarely present in clean coronary arteries. Scientists also have found abnormally high levels of antibodies against the bacterium and other indicators of its presence in patients with heart disease or who have suffered heart attacks.

All that is suggestive evidence, but not proof that it causes heart disease, experts say. It is possible that the bacterium may simply thrive in the fatty environment of the plaques and infect them only after heart disease has developed.

Immune System Plays Key Role

Penninger and Dr. Kurt Bachmaier of the Ontario Cancer Institute were not originally attempting to link chlamydia to heart disease. Rather, they were following up on earlier studies of myosin, a muscle protein that is found primarily in heart tissue.

Injecting mice with myosin triggers an autoimmune attack on the heart, producing heart disease. Penninger, Bachmaier and their colleagues found that part of the structure of myosin is virtually identical to proteins on the surface of chlamydia.

When they injected mice with fragments from these chlamydia proteins, they observed that the proteins stimulated an immune attack on the heart and blocked or partially blocked coronary arteries within 21 days, suggesting that a bacterial infection could do the same thing.

They speculate that a chlamydia infection anywhere in the body can trigger a localized immune attack that spreads to the heart.

Only the mice with overactive immune systems developed heart disease, however. That may be why most people do not develop heart disease, although they have been infected by chlamydia. And Shah cautioned that the lesions in the mouse arteries do not look quite the same as those in human atherosclerosis.

Nonetheless, the results suggest that attempts to use antibiotics to treat or prevent heart disease may be on the right track. Several retrospective studies have hinted that patients who have been treated with antibiotics, such a Zithromax, that kill chlamydia are less likely to have heart attacks.

But scientists will not be convinced of the drugs’ efficacy until the antibiotics are tested in trials where their effects are compared to those of a placebo. Pfizer, which manufactures Zithromax, has enrolled 3,500 patients in such a study. Grayston is heading a Pfizer/National Institutes of Health study, to begin next month, that will enroll 4,000 people. And Shah is heading a privately funded study that will include 1,400 people.

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Heart Disease and Bacteria

Canadian researchers have shown that injecting mice with proteins from chlamydia bacteria produces an atherosclerosis-like condition within 21 days, the first direct evidence of a link between bacteria and heart disease. They believe the same chlamydia bacteria are often found in atherosclerotic plaques, the fatty buildups on the interior of coronary arteries, shown below at right. Researchers believe the bacteria cause a person’s immune system to attack heart tissues, helping to increase the size of the plaques.

Heart attack: A narrowed artery blocks blood flow to the heart.

* Normal artery

Oxygen-rich blood flows freely through the artery.

* Atherosclerosis

The plaques can block the arteries, causing angina, or pieces can break off and lodge elsewhere, producing heart attacks.

Source: American Heart Assn.