Linking Infection to Heart Disease
By Denise Grady
Published: February 17, 1998
INFECTIONS in the mouth may play havoc elsewhere in the body, leading to blood clots that can bring on heart attacks and strokes, researchers reported yesterday.
Their findings, based on experiments in rabbits, add to a growing body of evidence in people linking certain chronic infections, including gum disease, to cardiovascular disease. Such infections have not been proved to cause heart disease, but the apparent connection has captured increasing attention from scientists in this country and in Europe.
The new study is the first to show that bacteria from the mouth can induce clotting, which is the pivotal event in most heart attacks and strokes. The research was done in Minneapolis at the University of Minnesota by a team lead by Dr. Mark Herzberg and Dr. Maurice Meyer, and presented at a meeting of the American Association for the Advancement of Sciene in Philadelphia.
They set out to study what happens when bacteria that are harmless in the mouth invade the bloodstream. That is likely to occur in people with infected gums, a condition also known as periodontal disease or pyorrhea. Gum disease develops when plaque deposits, which are a sticky film of bacteria on the teeth, grow and penetrate beneath the gumline. Bacteria begin to eat away the tissues around the teeth and to digest a pathway for themselves into the bloodstream.
If many gums are infected, the amount of damaged tissue open to invasion can be shockingly large. “Severe periodontal disease is the equivalent to a wound about eight square inches,” Dr. Herzberg said. “Imagine a wound that size on your skin, always ulcerated and exposed to a whole variety of bacteria.” Dental plaque contains about 300 species of bacteria, and a severe infection contains billions of bacteria.
People can usually prevent periodontal disease by brushing their teeth, using dental floss and having regular cleanings by a dentist or hygienist, Dr. Herzberg said. once the disease does set in, surgery and antibiotics may be needed to clear it up, and the treatment can take several months.
Dr. Herzberg and Dr. Meyer studied Streptococcus sanguis, the predominant bacterium in dental plaque. It is considered harmless, a normal inhabitant in a healthy mouth. But the researchers found that when they mixed the bacteria with human blood in test tubes, they led clots to form.
When billions of these bacteria were injected into rabbits, the effects were powerful. Within a minute, heart abnormalities appeared on the animals’ electrocardiograms, along with changes in blood pressure and breathing. Dr. Herzberg said those changes were probably due to clot formation in the coronary arteries and lungs.
The clots were caused by a protein on the surface of the bacterial cells, Dr. Herzberg said. Platelets stick to it and begin clumping because the bacterial protein resembles a normal human one, collagen, which is involved in the early stages of clotting. Platelets apparently mistake the bacterial substance for collagen, Dr. Herzberg said. Not all bacteria make the protein, and he and his colleagues found that only the strains that did were able to provoke strong responses in the animals.
“There’s no evidence this bacteria does anything in humans like what we see in rabbits,” Dr. Herzberg said. But, he added, “I think we’re showing a potential for these organisms to contribute to clotting events that may proceed to a heart attack.”
Clotting touches off most heart attacks and strokes by blocking arteries that feed the heart or brain. Even though most victims’ arteries have already been narrowed by fatty deposits, the deposits alone are not usually enough to choke off the blood supply: the final blow is nearly always the formation of a clot.
The idea that dental infections can cause problems in other parts of the body is a very old theory that has bobbed in and out of favor throughout the history of medicine, Dr. Herzberg said. Studying the medical literature, he found that the Assyrians proposed it in the 7th century B.C., but that it was then forgotten until the 16th century. The idea faded again and resurfaced in the 18th century, when Dr. Benjamin Rush, a Pennsylvania doctor and signer of the Declaration of Independence, reported that arthritis went away in some people after they had infected teeth pulled out.
Doctors now pay serious attention to the possibility that bacteria from the mouth can cause an array of problems if they get into the bloodstream. The potential link to arthritis is being studied in some laboratories, Dr. Herzberg said. Pregnant women with gum disease have been found to have a substantially increased risk of giving birth prematurely. And people with certain heart problems or artificial joints are thought to be especially vulnerable to such bacteria, and are advised to take antibiotics whenever they have dental work that might cause bleeding, which opens the bloodstream to bacterial invasion.
In addition, since 1989, about a half dozen studies have found that people with periodontal disease have an increased risk of heart disease and stroke. The increase has ranged from 20 percent to a doubling or tripling of risk, said Dr. James Beck, an epidemiologist in the dental school at the University of North Carolina in Chapel Hill. Dr. Beck said the evidence did not prove cause and effect, but it did suggest that gum disease might increase the risk of cardiosvascular disease.
Recent studies have also suggested that other infections may play a role in cardiovascular disease. The bacterium Chlamydia pneumoniae, which infects the lungs, is thought to damage arteries as well, and a common virus, cytomegalovirus, has also been blamed for causing arterial blockages in people who have had bypass surgery or heart transplants.
Dr. Thomas Quinn, an infectious disease researcher at Johns Hopkins University, said most researchers had come to believe that inflammation, a response of the immune system brought on by infection, plays an important role in cardiovascular disease, perhaps by injuring blood vessels and predisposing them to the buildup of fatty deposits. Antibiotics that attack Chlamydia pneumoniae are being tested to see if they can help prevent heart attacks in high-risk patients, he said.
“This is a brand new area of investigation,” he said, adding that it was conceivable, depending on how the studies turned out, that in the future some patients with heart disease would take antibiotics as part of their treatment. But Dr. Quinn also emphasized that those patients would not be told to take some pills and go back to eating butter and steak. The new theory does not challenge established findings about the roles of diet and exercise in heart disease, but just proposes another possible risk factor.
Dr. Quinn also compared the current state of knowledge to the one that existed 10 years ago for stomach ulcers. Many doctors then rejected the idea that bacteria, rather than stress or diet, might be the cause, but the theory was ultimately proved correct, and now most ulcers are cured with a treatment that includes antibiotics.
Dr. Charles Hennekens of the Harvard School of Public Health said: “This is an exciting area of research. It’s attractive and plausible, but not yet conclusive.” He said he and his colleagues would present data at a conference next month showing that they could find no connection between periodontal disease and cardiovascular problems in a study of more than 20,000 male doctors. “But that’s only one study,” he said. He described Dr. Herzberg’s work on clotting as an important finding that needed further study to determine its relevance to humans.
Dr. Herzberg also said that further studies were needed to determine whether dental disease and heart disease were really connected. But regardless of the outcome, he said, people should still try to prevent periodontal disease, or treat it promptly, because if it is left untreated, the teeth will eventually loosen and fall out.