Do oral bacteria cause cardiovascular disease?

Abstract

The viridans group streptococci, bacteria commonly found in dental plaque and harmless when localized to the mouth, might be responsible for triggering thromboembolic events following episodes of dental bacteremia, according to recent studies by Mark C. Herzberg and Maurice W. Meyer at the University of Minnesota School of Dentistry (Minneapolis, MN, USA). The finding that certain otherwise harmless oral bacteria might trigger thromboembolic events should be of particular concern to individuals suffering from periodontal disease. Indeed, epidemiological studies from independent laboratories have shown an increased risk of myocardial infarction associated with periodontitis [Mattila, K.J. et al. (1989) Br. Med. J. 298, 779–781; DeStefano, F. et al. (1993) Arch. Intern. Med. 153, 2489–2494; Beck, J. et al. (1996) J. Periodontol. 67 (suppl.), 1123–1137].Speaking at this year's meeting of the American Association for the Advancement of Science (Philadelphia, PA, USA), Herzberg described experiments in which a strain of Streptococcus sanguis expressing platelet aggregation-associated protein (PAAP+) induced dose-related electrocardiographic (ECG) abnormalities in rabbits within 30 seconds after infusion directly into the blood at doses of 4–40×109 cells. PAAP is believed to behave as a thrombogenic agent by mimicking the hemostatic structural domains of collagen. The rabbits exhibited difficulty in breathing, altered blood pressure, an increased heart rate, and decreased cardiac contractility—responses not observed with PAAP− S. sanguis. The ECG abnormalities were consistent with obstruction of coronary arteries and the development of myocardial infarction, but the studies have not yet been extended to determine whether the rabbits will ultimately go into cardiac arrest. Coincident with the ECG abnormalities was dose-dependent thrombocytopenia and accumulation of 111Indium-labeled platelets in the lungs. The notion that dental infections can have adverse health effects elsewhere in the body is a very old idea that can be traced back as far as the Assyrians of the 7th century BC, noted Herzberg, but this study is the first to suggest that bacteria from the mouth can lead to thrombosis and associated cardiovascular diseases.Herzberg and colleagues had previously shown that PAAP+ S. sanguis can induce both human and rabbit platelets to aggregate in vitro [Erickson, P.R. and Herzberg, M.C. (1995) Infect. Immun. 63, 1084–1088]. They concluded that platelet aggregation was triggered by the presence of the PAAP protein on the surface of the bacteria and that either the expression or the active conformation of PAAP can be altered, depending upon the type of collagen present in the culture medium on which the bacteria are grown. They found that aggregation was most pronounced when the PAAP+ strain of S. sanguis was grown in the presence of type I collagen, an observation that might be related to the notion that in endocarditis, the expression of PAAP in streptococci is controlled by proteins, including the various collagens, present on damaged heart valves.Low levels of oral bacteria can be detected in the blood after even mild perturbation of the teeth, including such ordinary events as chewing food or brushing one's teeth, but severe periodontal disease provides a portal through which large quantities of oral bacteria, or even small particles of dental plaque containing somewhere in the range of 300 different species of bacteria, can directly enter the blood. `A person with severe periodontis can have the equivalent of a wound as large as 7–9 square inches, and it can be there for 20 years or more. It becomes a chronic point of access for small fragments of plaque into the blood,' said Herzberg.In addition to ischemic heart diseases, ischemic diseases of the brain, including stroke, might be associated with the formation of thromboembolisms by oral bacteria. There has been an epidemiological association of dental condition and stroke, noted Herzberg. But in the future, Herzberg and his colleagues will continue to focus their research on ischemic heart disease. The next stage is to see whether the ischemic events observed in preliminary studies in rabbits persist for longer periods of time, and whether they can actually lead to an infarct.