Study Finds Direct Association Between Cardiovascular Disease and Periodontal Bacteria
Researchers report this week that older adults who have higher
proportions of four periodontal-disease-causing bacteria inhabiting
their mouths also tend to have thicker carotid arteries, a strong
predictor of stroke and heart attack. The study, published in the
current issue of the journal Circulation, was supported by four
agencies of the National Institutes of Health.
According to the authors, these data mark the first report of a direct association
between cardiovascular disease and bacteria involved in periodontal disease,
inflammation of the gums that affects to varying degrees an estimated 200 million
Americans. But the researchers say the findings are not proof that the bacteria
cause cardiovascular disease, directly or indirectly.
“What was interesting to us was the specificity of the association,” said
Moïse Desvarieux, M. D., Ph. D., the study’s lead author and an infectious
disease epidemiologist at Columbia University’s Mailman School of Public
Health and the University of Minnesota. “These same four bacteria were
there, they were always there in the analysis, and the relationship seems to
be pretty much, with one exception, limited to them.”
Desvarieux stressed that although the new data further illuminate a long-standing
scientific issue, they shed little light on the broader public health question
related to cardiovascular disease. The 657 people in the study had their oral
bacteria and carotid thickness evaluated at the same point in time. So Desvarieux
said, “It’s impossible to know which comes first, the periodontal
disease or thickening of the carotid artery.” The answer to that question
is fundamental to establishing causality in this case, whether chronic inflammation
or infection could have led to the atherosclerosis of the carotid arteries.
He and his colleagues noted that the public health information could come soon. “We
will re-examine the participants in less than three years, and, at that point,
we can better evaluate the progression of the atherosclerosis and, hopefully,
begin to establish a time frame underlying the diseases,” said Ralph Sacco,
M.D., M.S., associate chair of Neurology, professor of Neurology and Epidemiology,
and the director of the Stroke and Critical Care Division of Columbia University
College of Physicians and Surgeons. He also is an author on the paper.
The idea that oral bacteria shed from chronic gum infections, enter the circulatory
system, and possibly contribute to diseases of the heart and other body organs
once was widely accepted in medicine. The concept, known as the “focal
infection theory,” fell out of fashion by the 1940s, then resurfaced four
decades later with the publication of new data proposing a link.
Since then, a major sticking point in advancing the research has been simply
how to pursue the hypothesis. Lacking the scientific tools to track oral bacteria
in the body over several decades to determine if they directly trigger heart
disease, most previous studies pursued indirect evidence. These included various
measures of oral and cardiovascular health, which researchers then extrapolated
to the influence of the oral pathogens. Conspicuously missing from the debate
has been a large, well-designed study that in some way directly evaluates the
role of the oral pathogens themselves.
To fill this void, the National Institute of Dental and Craniofacial Research
launched the Oral Infections and Vascular Disease Epidemiology Study (INVEST),
a multi-disciplinary endeavor whose principal investigator is Dr. Desvarieux.
The study, which is the source of the paper published this week in Circulation,
will monitor the oral and cardiovascular health of a large, racially mixed group
of people. All enrollees in the study live in a northern section of Manhattan
in New York City and are age 55 or older. Participants are also members of the
Northern Manhattan Study (NOMAS), a prospective cohort study supported by NIH’s
National Institute of Neurological Disorders and Stroke. Dr. Sacco is principal
investigator of the companion NOMAS study.
“Although more than 600 bacteria have been shown to colonize the mouth,
each person tends to carry different proportions of these microbes,” said
Panos N. Papapanou, D.D.S, Ph.D., an author on the paper and professor and chair
of the Section of Oral and Diagnostics Sciences and director of the Division
of Periodontics at Columbia University School of Dental and Oral Surgery. He
noted that only a subset of bacteria tend to be dominant in dental plaque.
“We wanted to know during the baseline examination of the participants whether
it was true that the greater the proportion of so-called ‘bad’ bacteria
in the mouth, the higher the likelihood of a thickened carotid artery,” added
Papapanou, whose laboratory performed the periodontal microbiological analysis.
To get their answer, Desvarieux and colleagues collected on average seven dental
plaque samples from a total of 657 older adults enrolled in INVEST who had not
lost their teeth. The samples, taken from predetermined sites in the mouth, both
diseased and healthy, were measured for 11 oral bacteria, including four bacteria
widely regarded to be involved in causing periodontal disease: Actinobacillus
actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Treponema
denticola. The other seven bacteria served as controls, as their role in periodontal
disease was either neutral or has not yet been established.
Then, to evaluate their cardiovascular health, the participants received a carotid
intima-media thickness (IMT) measurement and provided a blood sample to determine
their C-reactive protein levels. C-reactive protein has been reported to be elevated
in people with periodontal disease, and recent studies found that testing for
this protein may be predictive of developing heart disease.
Controlling for several risk factors that might skew their data such as smoking
and diabetes, both of which are independently associated with these conditions
the scientists found the higher the levels of these periodontal-disease-causing
bacteria, the more likely people were to have thicker carotid arteries. Interestingly,
they noted no association between IMT, the periodontal pathogens, and C-reactive
protein levels, suggesting the protein is involved in another cardiovascular
Next, the scientists wondered whether the broad association might be due to the
four pathogens involved in causing periodontal disease, which combined accounted
for only 23 percent of the bacteria in dental plaque. If so, the finding would
provide added specificity to strengthen the case for the association.
“After re-analyzing the data, we found, with the exception of an oral bacterium
called Micromonas micros, the relationship was limited to these four established
oral pathogens,” said David Jacobs, Ph. D., another author and a professor
in the Division of Epidemiology at the University of Minnesota School of Public
“In other words, it was exactly what we hypothesized,” said Desvarieux.
However, he cautioned, “It now becomes crucial to follow the participants
over time and see whether these baseline findings hold up and further translate
into clinical disease.”
The study was supported by the NIH’s National Institute of Dental and Craniofacial
Research, the National Institute of Neurological Disorders and Stroke, National
Heart, Lung, and Blood Institute, and National Center for Research Resources.