Treating periodontal disease with scaling and root planing combined with a topical antibiotic gel can significantly lower the levels of two inflammatory proteins associated with a heightened risk of heart disease, scientists from the State University of New York at Buffalo report.

Blood drawn from 102 subjects with periodontal disease showed elevated levels of both C-reactive protein and fibrinogen, proteins associated with increased risk for heart disease and blood clotting. All of the subjects were free of other conditions that could cause elevated levels of the proteins.

Scientists from the UB School of Dentistry’s Department of Oral Biology divided the subjects into two groups to determine if periodontal therapy would be effective in lowering the levels of the heart disease markers. One group received scaling and root planing treatment while the second group received treatment with the topical antibiotic Atridox followed by scaling and root planing.

Based on a treatment regimen at three, six and nine months and blood samples taken at six weeks and at three, six, nine and 12 months, repeated periodontal treatment resulted in a significant reduction in the systemic levels of the inflammation markers, the UB scientists said.

“People who have high levels of CRP in their blood are at high risk of heart disease,” Dr. Sara Grossi, senior author of the study, said. “Our results showed that in people who had elevated levels of CRP at baseline, removal of dental plaque bacteria by scaling or scaling combined with topical antibiotics produced a statistically significant reduction, bringing CRP levels close to the low-risk level.”

“Both treatments also significantly reduced levels of fibrinogen in patients with elevated fibrinogen levels,” she added.

Source: American Dental Association. http://www.ada.org/prof/resources/pubs/adanews/adanewsarticle.asp?articleid=841%20

Poor dental hygiene increases risk of heart attack and stroke

Not brushing your teeth may increase the risk of heart attack and stroke, according to the results of a recent study.

More than 700 different types of bacteria live in the mouth. Poor dental hygiene allows these bacteria to flourish, and bleeding gums gives them direct access to the bloodstream. Professor Howard Jenkinson, from the University of Bristol, England, and colleagues who led the study found that certain types of bacteria stick onto platelets causing the platelets to clump together and encase the bacteria, thus creating small blood clots.

The formation of these small blood clots increases a person’s risk of having a stroke or a heart attack. It also enables the bacteria to evade detection by the immune system and protects them from antibiotics, thus explaining why antibiotics do not always work when they are used to treat infectious heart disease.

“Cardiovascular disease is currently the biggest killer in the western world. Oral bacteria such as Streptococcus gordoniiand Streptococcus sanguinis are common infecting agents, and we now recognise that bacterial infections are an independent risk factor for heart diseases,” Said Professor Jenkins in a press release. “In other words it doesn’t matter how fit, slim or healthy you are, you’re adding to your chances of getting heart disease by having bad teeth.”

  http://www.worldhealth.net/news/poor_dental_hygiene_increases_risk_of_he/

High Incidence of Actinobacillus Actinomycetemcomitans Infection in Acute Coronary Syndrome
Kaoru Sakurai1), Dongqing Wang2), Jun-ichi Suzuki1), Makoto Umeda2), Toshiyuki Nagasawa2), Yuichi Izumi2), Isao Ishikawa2)3) and Mitsuaki Isobe1)

Recent epidemiological studies suggest that periodontitis is an important risk factor for coronary heart disease (CHD). The aim of this study was to evaluate the association between periodontitis and CHD, particularly acute coronary syndrome (ACS), focusing on microbiological and immunological features.

Twenty-eight CHD patients, 15 with ACS and 13 with chronic CHD, were included in this study. Coronary angiography, periodontal examination, and dental radiography were performed in all patients. Subgingival plaque, saliva, and blood samples were analyzed for the periodontopathogens Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, and Prevotella intermedia using polymerase chain reaction.

Specific serum antibody titers to the 5 periodontal pathogens were determined by enzyme-linked immunosorbent assay. It was found that 33% of the ACS patients (5/15) harbored A. actinomycetemcomitans in oral samples, whereas no A. actinomycetemcomitans (0/13) was found in the chronic CHD patients (P < 0.05). Furthermore, ACS patients showed significantly higher serum IgG titers to A. actinomycetemcomitans (P < 0.05) compared with chronic CHD. More tooth loss and alveolar bone loss were noted in ACS patients than in chronic CHD patients, although the differences were not statistically significant.

Periodontal pathogens, particularly A. actinomycetemcomitans, may play a role in the development of ACS.

Treatment of Periodontitis and Endothelial Function

New England Journal of Medicine   Volume 356:911-920 March 1, 2007 Number 9        Maurizio S. Tonetti, D.M.D., Ph.D., Francesco D’Aiuto, D.M.D., Ph.D., Luigi Nibali, D.M.D., Ph.D., Ann Donald, Clare Storry, B.Sc., Mohamed Parkar, M.Phil., Jean Suvan, M.Sc., Aroon D. Hingorani, Ph.D., Patrick Vallance, M.D., and John Deanfield, M.B., B.Chir.

ABSTRACT

Background Systemic inflammation may impair vascular function, and epidemiologic data suggest a possible link between periodontitis and cardiovascular disease.

Methods We randomly assigned 120 patients with severe periodontitis to community-based periodontal care (59 patients) or intensive periodontal treatment (61). Endothelial function, as assessed by measurement of the diameter of the brachial artery during flow (flow-mediated dilatation), and inflammatory biomarkers and markers of coagulation and endothelial activation were evaluated before treatment and 1, 7, 30, 60, and 180 days after treatment.

Results Twenty-four hours after treatment, flow-mediated dilatation was significantly lower in the intensive-treatment group than in the control-treatment group (absolute difference, 1.4%; 95% confidence interval [CI], 0.5 to 2.3; P=0.002), and levels of C-reactive protein, interleukin-6, and the endothelial-activation markers soluble E-selectin and von Willebrand factor were significantly higher (P<0.05 for all comparisons). However, flow-mediated dilatation was greater and the plasma levels of soluble E-selectin were lower in the intensive-treatment group than in the control-treatment group 60 days after therapy (absolute difference in flow-mediated dilatation, 0.9%; 95% CI, 0.1 to 1.7; P=0.02) and 180 days after therapy (difference, 2.0%; 95% CI, 1.2 to 2.8; P<0.001). The degree of improvement was associated with improvement in measures of periodontal disease (r=0.29 by Spearman rank correlation, P=0.003). There were no serious adverse effects in either of the two groups, and no cardiovascular events occurred.

Conclusions Intensive periodontal treatment resulted in acute, short-term systemic inflammation and endothelial dysfunction. However, 6 months after therapy, the benefits in oral health were associated with improvement in endothelial function.

 Ann N Y Acad Sci. 2006 Nov;1088:251-64

Low-grade inflammation in chronic infectious diseases: paradigm of periodontal infections. Moutsopoulos NM, Madianos PN.Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.

Increasing evidence implicates periodontitis, a chronic inflammatory disease of the tooth-supporting structures, as a potential risk factor for increased morbidity or mortality for several systemic conditions including cardiovascular disease (atherosclerosis, heart attack, and stroke), pregnancy complications (spontaneous preterm birth [SPB]), and diabetes mellitus.

Cross-sectional, case-control, and cohort studies indicate that periodontitis may confer two- and up to sevenfold increase in the risk for cardiovascular disease and premature birth, respectively. Given the recently acquired knowledge that systemic inflammation may contribute in the pathogenesis of atherosclerosis and may predispose to premature birth, research in the field of periodontics has focused on the potential of this chronic low-grade inflammatory condition to contribute to the generation of a systemic inflammatory phenotype.

Consistent with this hypothesis clinical studies demonstrate that periodontitis patients have elevated markers of systemic inflammation, such as C-reactive protein (CRP), interleukin 6 (IL-6), haptoglobin, and fibrinogen. These are higher in periodontal patients with acute myocardial infarction (AMI) than in patients with AMI alone, supporting the notion that periodontal disease is an independent contributor to systemic inflammation. In the case of adverse pregnancy outcomes, studies on fetal cord blood from SBP babies indicate a strong in utero IgM antibody response specific to several oral periodontal pathogens, which induces an inflammatory response at the fetal-placental unit, leading to prematurity.

The importance of periodontal infections to systemic health is further strengthened by pilot intervention trials indicating thatperiodontal therapy may improve surrogate cardiovascular outcomes, such as endothelial function, and may reduce four- to fivefold the incidence of premature birth. Nevertheless, further research is needed to fully discern the underlying mechanisms by which local chronic infections can have an impact on systemic health, and in this endeavor periodontal disease may serve as an ideal disease model.

Atherosis: Volume 183, Issue 2, Pages 342-348 (December 2005)
21 of 29

Associations between IgG antibody to oral organisms and carotid intima–medial thickness in community-dwelling adults
James D. Becka, Paul Ekeb, Dongming Linc, Phoebus Madianosd, David Coupere, Kevin Mossa, John Elterf, Gerardo Heissg, Steven Offenbacherc
Received 6 December 2004; received in revised form 25 February 2005; accepted 21 March 2005.
Abstract
Aims
The aims of this study are to describe the relationships between IgG antibodies to 17 oral organisms and atherosclerosis as indexed by carotid intima–medial wall thickness (IMT) and to evaluate the role of smoking.
Methods and results
Our study is based on a subset of participants in the Atherosclerosis Risk in Communities (ARIC) Study, who received a complete periodontal examination during visit 4 (1996–1998). The outcome was mean carotid IMT≥1mm assessed by B-mode ultrasound. The exposures were serum IgG antibody levels against 17 periodontal organisms using a whole bacterial checkerboard immunoblotting technique. Evaluation of all 17 antibodies indicated that antibody to Campylobacter rectus resulted in the best-fitting model (OR=2.3, 95% CI=1.83–2.84) and individuals with both high C. rectus and Peptostreptococcus micros titers had almost twice the prevalence of IMT≥1mm than those with only a high C. rectus antibody (8.3% versus 16.3%). Stratification by smoking indicated that all microbial models significant for smokers were also significant for never smokers except for Porphyromonas gingivalis (p=0.08).

Conclusions
This is the first study to report a relationship between IgG antibody reactive to oral organisms and subclinical atherosclerosiswith significant relationships evident in both ever and never smokers.

1: Eur J Vasc Endovasc Surg. 2007 Jul;34(1):102-6. Epub 2007 May 2.

Oral bacteria are a possible risk factor for valvular incompetence in primary varicose veins.

Kurihara N, Inoue Y, Iwai T, Sugano N, Umeda M, Huang Y, Ishikawa I.

Department of Vascular and Applied Surgery and Periodontology, Tokyo Medical and Dental University Graduate School of Medicine and Dentisty, Tokyo, Japan. [email protected]

OBJECTIVES: To investigate a possible link between valvular incompetence in primary varicose veins and chronic infection of periodontal disease by assessing the presence of oral bacteria in the great saphenous vein from patients with varicose veins and control subjects. MATERIAL AND METHODS: Forty-four primary varicose vein patients were enrolled in the study. 12 control saphenous veins were obtained from patients undergoing peripheral arterial bypass without clinical evidence of venous reflux. In total, 56 saphenous vein specimen (44 varicose veins and 12 control veins) were examined for 7 periodontal bacteria using a polymerase chain reaction (PCR) method. RESULTS: Of the 44 primary varicose vein patients, 31 patients were women and mean age was 59 years (range, 39-79 years). PCR examination of the diseased vein specimens showed that 48% were positive for at least one of 7 periodontal bacterial DNA. No bacteria were detected in the control specimens. CONCLUSION: Bacterial colonisation or infection of varicose veins is a frequent event although we were not able to establish whether this is a cause or consequence of the development of varices but this could be considered a risk factor for the development of varices.

Periodontitis May Increase Risk of Peripheral Arterial Disease

Chen YW, Umeda M, Nagasawa T et al.  Eur J Vasc Endovasc Surg 2008; 35(2): 153-158.

A case controlled study looked at the association between periodontitis and PAD.  25 subjects having bypass surgery were matched with 32 healthy controls matched for age, sex, race and smoking history.  DNA detection was used to look for periodontal pathogens.  All subjects underwent a clinical periodontal examination and also had levels of IgG against the perio pathogens registered along with measures of their inflammatory cytokine levels.

Patients with PAD had a signifcantly higher prevalence of periodontitis and fewer teeth.   DNA from the periodontal pathogens was detected in the arterial samples., higher IgG titers as well as significantly increased levels of the cytokines.

Regression analysis indicated that periodontis is associated with a five-fold increase in risk for PAD.  The authors recognized that this does not confirm a causal relationship.

UC Davis study identifies C-reactive protein as cause of blood clot formation

(SACRAMENTO, Calif.) — Further underscoring the limitations of cholesterol screening in assessing a patient’s risk for heart disease, a new study by UC Davis physicians is the first to conclusively link C-reactive proteins (CRP) to formation of blood clots, a major cause of heart attacks, strokes and other vascular disease. Until now, CRP had been recognized mainly as a risk marker of heart disease. The study appears in the Jan. 25 print edition of the journal Circulation, a publication of the American Heart Association, and is available on the Web at www.circulationaha.org.

“The study provides further conclusive evidence that CRP, until now viewed as an ‘innocent bystander’ in the formation of heart disease, is in fact a key culprit that causes inflammation in the arteries, resulting in formation of clots and plaque that lead to heart attacks and strokes,” said Ishwarlal Jialal, professor of pathology and director of the Laboratory for Atherosclerosis and Metabolic Research at UC Davis School of Medicine and Medical Center.

The study demonstrates that CRP causes cells in the arteries, known as human aortic endothelial cells, to produce higher levels of an enzyme that inhibits the breakdown of clots. The enzyme, plasminogen activator inhibitor-1 (PAI-1) is also a strong risk marker for heart disease, especially in diabetics. The study used a variety of techniques to convincingly show how CRP activates PAI-1 in aortic cells, causing lesions in the arteries that ultimately lead to formation of plaque and blood clots.

The study underscores the need to use CRP screening to more accurately assess at-risk populations, according to Jialal, who is the Robert E. Stowell Endowed Chair in Experimental Pathology.

“Based on these findings, if a patient has normal cholesterol but high levels of CRP, an aggressive course of treatment is recommended to help the patient reduce the risk of heart attack, stroke and other heart diseases,” said Jialal. “By relying on cholesterol alone, a physician could significantly underestimate a patient’s risk level.”   High CRP levels can occur in otherwise healthy individuals, according to the study. Patients with high levels of CRP can reduce risk by losing weight, exercising on a regular basis, stopping cigarette smoking, or taking statin drugs, Jialal added.

The study also closely links CRP and PAI-1 to diabetes and metabolic syndrome, a disorder characterized by a disproportionate amount of abdominal fat, elevated blood pressure, blood sugar and triglycerides and low levels of HDL, the “good” kind of cholesterol.

“In another important discovery, this study shows that in the presence of high blood-glucose levels, CRP is especially active in the stimulation of PAI-1. As a result, the effect of CRP is especially acute for patients with diabetes and metabolic syndrome,” said Sridevi Devaraj, a co-investigator and assistant professor of pathology at UC Davis. “Given the current pandemic of obesity which increases one’s risk of diabetes, the study’s insights about the active role of CRP and PAI-1 in heart disease are especially valuable.”

The new study adds to the findings of another landmark study on CRP by Jialal’s team at UC Davis that showed CRP actually damages the blood vessel wall by blocking a critical “protector” protein and inhibiting nitric oxide.

“Interestingly, the new study indicates that activation of PAI-1 was unrelated to the nitric oxide inhibition identified in the earlier study,” said Jialal. “This indicates that CRP has multiple, independent effects that cause heart disease.”

Porphyromonas gingivalis promotes murine abdominal aortic aneurysms via matrix metalloproteinase-2 induction

Aoyama N, Suzuki J, Wang D, Ogawa M, Kobayashi N, Hanatani T, Takeuchi Y, Izumi Y, Isobe M. Porphyromonas gingivalis promotes murine abdominal aortic aneurysms via matrix metalloproteinase-2 induction. J Periodont Res 2010; doi: 10.1111/j.1600-0765.2010.01326.x. © 2010 John Wiley & Sons A/S

Background and Objective:  Abdominal aortic aneurysm (AAA) is a common and lethal disorder, and MMPs are highly expressed in AAA lesions. Large numbers of periodontopathic bacteria have been reported to be present in specimens obtained from the aortic walls of patients with an AAA. The purpose of this study was to analyze the influence of periodontopathic bacteria on AAA dilatation.

Material and Methods:  AAAs were produced in mice by the periaortic application of 0.25 m CaCl2, and NaCl was used as a control. The mice were inoculated once weekly with live Porphyromonas gingivalis, live Aggregatibacter actinomycetemcomitans or vehicle.

Results:  Four weeks after the periaortic application of either CaCl2 or NaCl, a significant increase was observed in the aortic diameter ofP. gingivalis-challenged mice compared with the vehicle control mice (p < 0.05), whereas there was no statistically significant increase in the aortic diameter of the A. actinomycetemcomitans-challenged mice. Immunohistochemical analysis found significantly higher numbers of CD8-positive and MOMA2-positive cells and significantly higher levels of MMP-2 in the aneurysmal samples of P. gingivalis-challenged mice compared with control mice. Live P. gingivalis promoted a significant proliferation of splenocytes in comparison with P. gingivalis-lipopolysaccharide and live A. actinomycetemcomitans (p < 0.05).

Conclusion:  These findings demonstrate that challenge with P. gingivalis, but not with A. actinomycetemcomitans, can accelerate, or even initiate, the progression of experimental AAA through the increased expression of MMPs

Oral Microbiology and Immunology

Volume 24 Issue 1, Pages 64 – 68

Detection of oral bacteria in cardiovascular specimens

K. Nakano 1 , H. Nemoto 1 , R. Nomura 1 , H. Inaba 2 , H. Yoshioka 3 , K. Taniguchi 4 , A. Amano 2 , T. Ooshima 1

ABSTRACT

Background/aims: Oral bacteria, including cariogenic and periodontal pathogens, are thought to be etiological factors in the development of cardiovascular diseases. To define this relationship, we analyzed the distribution of oral bacterial species in cardiovascular specimens.

Method: Following acceptance into the study, 203 consecutive patients were analyzed, from whom 82 aortic valve specimens, 35 mitral valve specimens, and 86 aortic aneurysmal wall specimens, of which 16 contained aneurysmal thrombus tissues, were obtained. In addition, a total of 58 dental plaque specimens were collected from the same group of patients who underwent heart valve replacement or removal of aortic aneurysms. Bacterial DNA was extracted from both cardiovascular tissues and dental plaque in those cases and then species-specific polymerase chain reaction assays were used to analyze the occurrences of six oral streptococcal and six periodontal bacterial species.

Results:  Streptococcus mutans was the most frequently detected species in the cardiovascular specimens, followed by Aggregatibacter actinomycetemcomitans. As for dental plaque specimens from patients who underwent cardiovascular operations, most of the tested periodontitis-related species as well as oral streptococci were detected at high frequencies. Furthermore, the positive rate of S. mutans in cardiovascular specimens from patients whose dental plaque specimens were also positive for S. mutans was 78%, which was significantly higher than any other tested species when the same analysis was performed.

Conclusion: Our results suggest that specific oral bacterial species, such as S. mutans and A. actinomycetemcomitans, are related to bacteremia and may be etiologic factors for the development of cardiovascular diseases.

JOURNAL OF MAXILLOFACIAL AND ORAL SURGERY
Volume 8, Number 2, 108-113, DOI: 10.1007/s12663-009-0028-5
RESEARCH PAPER
Prevalence of periodontal pathogens in coronary atherosclerotic plaque of patients undergoing coronary artery bypass graft surgery
Jaideep Mahendra, Little Mahendra, V. M. Kurian, K. Jaishankar and R. Mythilli

Abstract
Background
Chronic bacterial infections have been associated with an increased risk for atherosclerosis and coronary artery disease. The ability of oral pathogens to colonize in coronary atheromatous plaque is well known. The aim of our study was to detect the presence of four common periodontal pathogens in coronary plaques. We detected the presence of 16S rRNA of Treponema denticola, Eikenella Corrodens, Porphyromonas gingivalis and Campylobacter rectus in subgingival and atherosclerotic plaques of CABG surgery by using Polymerase Chain Reaction.
Methods
51 patients in the age group of 40 to 80 years with chronic periodontitis were recruited for the study. These patients were suffering from Coronary Artery Disease (CAD) and underwent Coronary Artery Bypass Grafting (CABG). DNA was extracted from the subgingival plaque and coronary atheromatous plaque samples. Universal Primer for the general detection of bacterial DNA and the primers for T.denticola, E. Corrodens, C.rectus and P.gingivalis were used to amplify part of 16SrRNA gene by Polymerase Chain Reaction.
Results
T.denticola, E.corrodens, C.rectus and P.gingivalis were detected in 49.01 %, 27.45 %, 21.51% and 45.10% of atherosclerotic plaque samples. In both subgingival and coronary plaque samples, T. denticola was detected in 39.21% of the cases, E.corrodens in 19.60%, C.rectus in 11.76% and P.gingivalis in 39.22% of the cases respectively.
Conclusion
Our study revealed the presence of significant bacterial DNA of oral pathogens in coronary plaques. This suggests possible relationship between periodontal infection and atherosclerosis and can help devise preventive treatment strategies.

Mechanisms involved in the association between periodontal diseases and cardiovascular disease

1. R Teles1,
2. C-Y Wang3

Article first published online: 11 JAN 2011

DOI: 10.1111/j.1601-0825.2010.01784.x

© 2011 John Wiley & Sons A/S

Issue

New research finds link between gum disease, acute heart attacks

By DAVID WILLIAMSON
UNC News Services

CHAPEL HILL — Heart attack survivors who suffer advanced gum disease show significantly higher levels of a protein in their blood called C-reactive protein (CRP) than such patients without gum disease, new University of North Carolina at Chapel Hill research indicates.

The findings, presented Sunday (Nov. 12) during a news conference at the annual American Heart Association meeting in New Orleans, suggest that the presence of gum disease might increase the risk of a second heart attack in people with a history of heart disease.

“Not only did the heart attack patients with periodontal disease have higher levels of CRP than those without gum disease, but the CRP levels were directly related to the severity of the gum disease,” said Dr. Efthymios N. Deliargyris, an interventional cardiologist and a member of the Center for Oral and Systemic Diseases at UNC-CH. “The more severe the gum disease, the higher the CRP levels.”

Besides Deliargyris, also an instructor in medicine at the UNC-CH School of Medicine, study investigators were Drs. Steven Offenbacher, professor of periodontology and center director, James D. Beck, professor of dental ecology, both at the UNC-CH School of Dentistry, and Sidney C. Smith Jr., chief of cardiology and past president of the American Heart Association.

“We know a lot of risk factors for heart attacks, including high blood pressure, high cholesterol, diabetes and cigarette smoking, but all those combined only explain about two-thirds of heart attacks,” Deliargyris said. “Since about a third of people who suffer heart attacks don’t have those risk factors, there’s a wide search going on for other conditions that may contribute to increased risk.”

Studies at UNC-CH and elsewhere have linked periodontal disease — an advanced form of gingivitis — with increased risk of heart attacks, but it has been unclear what the two conditions have in common, the physician said.

“The one thing we know the two conditions share is that they tend to initiate an immune response, also called an inflammatory response, in the body,” he said. “The most common marker for this response is this C-reactive protein, which is considered predictive of future adverse events like heart attack.”

To learn how common severe gum disease was in heart attack victims, the UNC-CH team conducted their pilot study of 38 heart attack patients and matched them with a comparable group of 38 other people without known heart disease. Researchers found a high percentage of the former had periodontal disease — 85 percent — as compared with only 29 percent of the controls.

“The most exciting finding was that among people with a heart attack, those with periodontal disease had much higher CRP levels than those with a heart attack but no periodontal disease,” Deliargyris said. “It seems that the presence of periodontal disease on top of a heart attack has a synergistic effect and a very accentuated CRP release.”

Despite its small size, the study findings are the first of their kind and potentially very important, he said.

“This gives us an insight into possible mechanisms underlying the association between gum disease and heart disease,” Deliargyris said. “Now we believe that patients with a heart attack and periodontal disease have an exaggerated inflammatory response with higher CRP levels that might put them at risk for future heart attacks. This work also raises the possibility that by treating severe gum disease in people with heart attacks, we might be able to reduce their CRP levels and their risk of another heart attack.”

Age-dependent associations between chronic periodontitis/edentulism and risk of coronary heart disease

Source: Circulation 2008 Apr1;117(13):1688-74 Authors: Dietrich T, Jimenez M, Krall Kaye EA, Vokonas PS, Garcia RI Summary of research: • Recognize the relationship between periodontitis and coronary heart disease (CHD), (angina, myocardial infarction or fatal CHD) in men.
• Significant association between periodontitis and CHD among men <60 years of age independent of diabetes, blood pressure, smoking, cholesterol etc.
• No such association found among men > 60 years of age.

Results and conclusions: • Chronic periodontitis is associated with incidence of coronary heart disease among younger men (<60), independent of established cardiovascular risk factors. Key take-away • Male patients with chronic periodontal disease who are below the age of 60 have a higher risk of angina, heart attack or fatal coronary heart disease compared to men over the age of 60. Implementation strategies: • During routine risk assessment with all male patients under the age of 60 the clinician should make a statement (see sample below) regarding this research and comment about the importance of ongoing periodontal evaluation at each dental hygiene appointment.

Comparison of C-Reactive Protein and Low-Density Lipoprotein Cholesterol Levels in the Prediction of First Cardiovascular Events                http://content.nejm.org/cgi/content/abstract/347/20/1557
Paul M. Ridker, M.D., Nader Rifai, Ph.D., Lynda Rose, M.S., Julie E. Buring, Sc.D., and Nancy R. Cook, Sc.D.

ABSTRACT

Background Both C-reactive protein and low-density lipoprotein (LDL) cholesterol levels are elevated in persons at risk for cardiovascular events. However, population-based data directly comparing these two biologic markers are not available.

Methods C-reactive protein and LDL cholesterol were measured at base line in 27,939 apparently healthy American women, who were then followed for a mean of eight years for the occurrence of myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. We assessed the value of these two measurements in predicting the risk of cardiovascular events in the study population.

Results Although C-reactive protein and LDL cholesterol were minimally correlated (r=0.08), base-line levels of each had a strong linear relation with the incidence of cardiovascular events. After adjustment for age, smoking status, the presence or absence of diabetes mellitus, categorical levels of blood pressure, and use or nonuse of hormone-replacement therapy, the relative risks of first cardiovascular events according to increasing quintiles of C-reactive protein, as compared with the women in the lowest quintile, were 1.4, 1.6, 2.0, and 2.3 (P<0.001), whereas the corresponding relative risks in increasing quintiles of LDL cholesterol, as compared with the lowest, were 0.9, 1.1, 1.3, and 1.5 (P<0.001). Similar effects were observed in separate analyses of each component of the composite end point and among users and nonusers of hormone-replacement therapy. Overall, 77 percent of all events occurred among women with LDL cholesterol levels below 160 mg per deciliter (4.14 mmol per liter), and 46 percent occurred among those with LDL cholesterol levels below 130 mg per deciliter (3.36 mmol per liter). By contrast, because C-reactive protein and LDL cholesterol measurements tended to identify different high-risk groups, screening for both biologic markers provided better prognostic information than screening for either alone. Independent effects were also observed for C-reactive protein in analyses adjusted for all components of the Framingham risk score.

Conclusions These data suggest that the C-reactive protein level is a stronger predictor of cardiovascular events than the LDL cholesterol level and that it adds prognostic information to that conveyed by the Framingham risk score.
Source Information

From the Center for Cardiovascular Disease Prevention and the Divisions of Preventive Medicine (P.M.R., L.R., J.E.B., N.R.C.) and Cardiology (P.M.R.), Brigham and Women’s Hospital and Harvard Medical School; and the Department of Laboratory Medicine, Children’s Hospital and Harvard Medical School (N.R.) — all in Boston.

Ann Thorac Surg 2004;77:537-543
© 2004 The Society of Thoracic Surgeons

Role of oral bacterial flora in calcific aortic stenosis: an animal model

David J. Cohen, MDa*, David Malave, MDa, John J. Ghidoni, MDb, Panagiotis Iakovidis, MDc, Mona M. Everett, PhDb,c,d, Shenghong You, MDd, Youhong Liu, MDd, Barbara D. Boyan, PhDd     Abstract
BACKGROUND: Calcific aortic stenosis is a major public health problem in the United States. The mechanism of calcification remains unclear. The hypothesis that low grade chronic or recurrent bacterial endocarditis with specific calcifiable bacteria is a cause of calcification of the aortic valves was investigated using an animal model. Such bacteria are typically present as part of the normal human oral flora.METHODS: Forty New Zealand white rabbits were divided into four groups: group 1, control (1 ml of normal saline); group 2, Corynebacterium matruchotti 100,000 colonies; group 3, Streptococcus sanguis II 10 colonies; and group 4, C matruchotti 100,000 colonies plus S sanguis II 10 colonies. Animals were inoculated with bacteria through a flexible catheter placed through the aortic valve through a right carotid cut down. Inoculations were repeatedevery 3 days the first 2 weeks and then twice a week thereafter. At postmortem examination the aortic valves were harvested, embedded in paraffin, and stained with von Kossa stain. They were also examined by scanning and transmission electron micrography.

RESULTS: Group 4 had 93.3% large calcifications (confluent calcium densities that are easily recognized with minimal magnification) and 6.6% small microcalcifications (dustlike microscopic particles requiring a compound microscope to appreciate) of the aortic valves. Group 3 exhibited large calcification in 20% and small in 40% of the aortic valves. Group 1 and group 2 had no evidence of calcification.

CONCLUSIONS: These results suggest that recurrent low-grade endocarditis from calcifying oral bacteria, particularly when occurring with synergistic strains, may be one cause of calcific aortic stenosis.

Abstract Journal of Periodontology 2007, Vol. 78, No. 2, Pages 322-327 (doi:10.1902/jop.2006.060081)
Evaluation of the Incidence of Periodontitis-Associated Bacteria in the Atherosclerotic Plaque of Coronary Blood Vessels Maciej Zaremba,* ­Renata Górska,* ­Piotr Suwalski, and ­Jan Kowalski*­

Background: Unstable atherosclerotic plaque is a dangerous clinical condition, possibly leading to acute coronary deficiency resulting in cardiac infarction. Questions about the role of inflammatory factors in the formation of pathological lesions in the endothelium of coronary vessels have often been raised. This condition may be caused by bacteria that are able to initiate clot formation in a blood vessel, destabilizing an atherosclerotic plaque that is already present. The sources of these pathogens are chronic inflammatory processes occurring in the host, including periodontal disease, which is one of the most frequent conditions. The aim of this study was to evaluate the incidence of selected anaerobic bacteria in subgingival and atherosclerotic plaque in patients treated surgically because of coronary vessel obliteration.

Methods: The study was performed on 20 individuals with chronic periodontitis. Subgingival plaque was collected from periodontal pockets >5 mm. DNA testing was used to identify eight pathogens responsible for periodontal tissue destruction. Material from atherosclerotic plaques was collected from the same patients during bypass surgery, and DNA testing by the same method was performed.

Results: In 13 of 20 patients, the pathogens most frequently found in severe chronic periodontitis were also found in coronary vessels. In 10 cases, those species of bacteria were also present in atherosclerotic plaque. The most frequently identified bacteria werePorphyromonas gingivalis and Treponema denticola.

Conclusions: In patients with the severe form of chronic periodontitis, it seems that clinical attachment loss is not associated with bacterial permeability into coronary vessels. What is important is the presence of an active inflammatory process expressed by a significantly higher bleeding index in those patients in whom the examined bacterial species were found in atherosclerotic plaque.

Inflammation, heat shock proteins and periodontal pathogens in atherosclerosis: an immunohistologic study.

Ford PJ, Gemmell E, Chan A, Carter CL, Walker PJ, Bird PS, West MJ, Cullinan MP, Seymour GJ.

Oral Biology and Pathology, School of Dentistry, The University of Queensland, Brisbane, Australia. [email protected]

BACKGROUND: Inflammation is a significant component of atherosclerosis lesions. Bacteria, including periodontopathogens, have been demonstrated in atherosclerotic plaques and cross-reactivity of the immune response to bacterial GroEL with humanheat shock protein 60 has been suggested as a link between infections and atherosclerosis.

METHODS: In this study, the nature of the inflammatory infiltrate and the presence of human heat shock protein 60 and GroEL were examined in 31 carotid endarterectomy specimens. Additionally, monoclonal antibodies were used to detect the presence of six bacteria, including those implicated in periodontal disease. RESULTS: The inflammatory cell infiltrate of the lesions was dominated by CD14(+) macrophages and CD4(+) T cells. Most cells of the infiltrate as well as the endothelium were HLA-DR(+), indicating activation; however, there was an absence of CD25 expression, demonstrating that the activated T cells were not proliferating. Few CD1a(+) and CD83(+) cells were noted.

Human heat shock protein 60 expression was evident on endothelial cells and cells with the appearance of smooth muscle cells and lymphocytes. GroEL and bacteria were detected within intimal cells. Chlamydia pneumoniae, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia, Prevotella intermedia, and Actinobacillus actinomycetemcomitans were found in 21%, 52%, 34%, 34%, 41%, and 17% of arteries, respectively. CONCLUSION: These results give evidence for a specific immune response associated with atherosclerosis. Whether bacteria initiate the observed inflammation in atherosclerotic lesions is not clear; however, the present study shows that maintenance of inflammation may be enhanced by the presence of periodontopathic bacteria.

Related Links

• Cross-reactivity of GroEL antibodies with human heat shock protein 60 and quantification of pathogens in atherosclerosis. [Oral Microbiol Immunol. 2005]
• Characterization of heat shock protein-specific T cells in atherosclerosis. [Clin Diagn Lab Immunol. 2005]
• Anti-P. gingivalis response correlates with atherosclerosis. [J Dent Res. 2007]
• Periodontal pathogens in atheromatous plaques. A controlled clinical and laboratory trial. [J Periodontal Res. 2004]
• Immunology of atherosclerosis. Demonstration of heat shock protein 60 expression and T lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions. [Am J Pathol. 1993]

Periodontal Disease, C-Reactive Protein and Overall Health

Elevated C-reactive protein (CRP)levels increase the risk for cardiovascular disease

Researchers have known for quite some time that elevated C-reactive protein (CRP) levels increase the risk for cardiovascular disease. A recent study published in The New England Journal of Medicine identified elevated CRP levels as a stronger predictor of heart attacks than elevated cholesterol levels, and recommended CRP and cholesterol screening for accurate risk assessment of cardiovascular disease.

However, many clinicians were unclear of the cause of elevated CRP levels. A study published earlier this year in the Journal of Periodontology reported that inflammatory effects from periodontal disease, a chronic bacterial infection of the gums, cause oral bacterial byproducts to enter the bloodstream and trigger the liver to make proteins such as CRP that inflame arteries and promote blood clot formation. Study Abstract

“Periodontal disease needs to be considered as a major contributor to increased levels of CRP by the medical community,” said Dr. Steven Offenbacher, member of the American Academy of Periodontology.

Previous studies reported that inflammatory effects from periodontal disease could cause oral bacterial byproducts to enter the bloodstream and trigger the liver to make proteins such as CRP that inflame arteries. In addition, these effects may cause blood clots that contribute to clogged arteries leading to heart attacks or strokes.

“What makes the recent findings noteworthy is that oral examinations were conducted on more than 5,000 adults in four U.S. communities already participating in a study to determine the risk of atherosclerosis,” said Offenbacher. “This is most likely the largest study confirming that periodontal disease and body mass index are jointly associated with increased levels of CRP in healthy adults.”

He added, “To reduce levels of CRP, and presumably the risk of cardiovascular disease, not only would it be important to lose weight if you are overweight, but it would also be important to get your gums treated.”

CRP testing is now available in many hospitals and health centers. The American Heart Association and the Centers for Disease Control and Prevention are developing a summary on whether CRP levels should be routinely tested to diagnose heart disease or to monitor progress of treatments.

“Based on this information and the potential to prevent heart attacks and strokes, I foresee patients receiving routine CRP testing in their dentist or periodontist office in the near future,” said Dr. Gordon Douglass, president of the American Academy of Periodontology. “This could help early diagnosis of potential heart disease sooner rather than later, as most people see their dentist or periodontist at minimum two times a year.”

source: http://www.perio.org/consumer/happy-heart.htm

Repeated Treatment Of Gum Disease Reduces Levels Of Inflammatory Factors Known To Increase Heart Disease Risk

ScienceDaily (Apr. 8, 2004) — BUFFALO, N.Y. — Reinforcing the relationship between periodontal disease and heart disease, oral biologists from the University at Buffalo have shown that levels of two inflammatory proteins known to raise the risk of heart disease can be reduced substantially by regularly treating existing gum infections.

“You can have significant effects in other parts of the body by treating local problems,” said Sara Grossi, D.D.S., senior research scientist in the Department of Oral Biology, UB School of Dental Medicine and senior author on the study. “That’s why treating these infections is so important.”

Results of the study were presented at the International Association for Dental Research meeting held March 10-13 in Hawaii by Owais A. Farooqi, a doctoral student working with Grossi in UB’s Periodontal Disease Research Center.

The current study reports findings from 102 patients with periodontal disease who were randomized to two study groups and followed for one year. One group received standard “mechanical” treatment for periodontal disease, called scaling and root planning. The other group had the antibiotic gel Atridox™ applied to their gums before mechanical treatment.

Blood drawn at the start of the study showed that all patients had high levels of an inflammatory marker called C-reactive protein, which is known to put individuals at high risk for heart disease, and of fibrinogen, a protein involved in promoting blood clots. All patients were free of other conditions that could cause inflammatory proteins to show up in their blood stream

Both groups received their designated treatment at baseline, 3, 6 and 9 months. Blood samples were taken at baseline, and at 6 weeks, 3, 6, 9 and 12 months. At the end of 12 months, results showed that systemic levels of markers of inflammation decreased with repeated treatment.

“People who have high levels of CRP in their blood are at high risk of heart disease,” Grossi said. “Our results showed that in people who had elevated levels of CRP at baseline, removal of dental plaque bacteria by scaling or scaling combined with topical antibiotics produced a statistically significant reduction, bringing CRP levels close to the low-risk level. Both treatments also significantly reduced levels of fibrinogen in patients with elevated fibrinogen levels.

Grossi’s lab next will assess levels of cytokines — additional markers of inflammation — and how periodontal therapy affects them. “This work will provide additional information on the systemic effect or benefit of treating gum infection and provide valuable information on the relationship between gum disease and heart disease and diabetes.

Additional researchers on the study were Alex Ho, statistician, and Robert J. Genco, D.D.S., Ph.D., SUNY Distinguished professor, from the UB Department of Oral Biology, and J. Steven Garrett from Atrix Laboratories Inc.

Prim Dent Care. 2007 Apr;14(2):59-66.

Cardiovascular and oral disease interactions: what is the evidence?

Ford PJ, Yamazaki K, Seymour GJ.

Oral Biology and Pathology, School of Dentistry, University of Queensland, Brisbane, Australia. [email protected]

This paper reviews the evidence for the interaction of oral disease (more specifically, periodontal infections) with cardiovascular disease. Cardiovascular disease is a major cause of death worldwide, with atherosclerosis as the underlying aetiology in the vast majority of cases. The importance of the role of infection and inflammation in atherosclerosis is now widely accepted, and there has been increasing awareness that immune responses are central to atherogenesis. Chronic inflammatory periodontal diseases are among the most common chronic infections, and a number of studies have shown an association between periodontal disease and an increased risk of stroke and coronary heart disease. Although it is recognised that large-scale intervention studies are required, pathogenic mechanism studies are nevertheless required so as to establish the biological rationale. In this context, a number of hypotheses have been put forward; these include common susceptibility, inflammation via increased circulating cytokines and inflammatory mediators, direct infection of the blood vessels, and the possibility of cross-reactivity or molecular mimicry between bacterial and self-antigens. In this latter hypothesis, the progression of atherosclerosis can be explained in terms of the immune response to bacterial heat shock proteins (HSPs). Because the immune system may not be able to differentiate between self-HSP and bacterial HSP, an immune response generated by the host directed at pathogenic HSP may result in an autoimmune response to similar sequences in the host. Furthermore, endothelial cells express HSPs in atherosclerosis, and cross-reactive T cells exist in the arteries and peripheral blood of patients with atherosclerosis. Each of these hypotheses is reviewed in light of current research. It is concluded that although atherosclerotic cardiovascular disease is almost certainly a multifactorial disease, there is now strong evidence that infection and inflammation are important risk factors. As the oral cavity is one potential source of infection, it is wise to try to ensure that any oral disease is minimised. This may be of significant benefit to cardiovascular health and enables members of the oral health team to contribute to their patients’ general health.

Periodontal Infections and Coronary Heart Disease
Role of Periodontal Bacteria and Importance of Total Pathogen Burden in the
Coronary Event and Periodontal Disease (CORODONT) Study
Axel Spahr, DDS; Elena Klein, DDS; Natalie Khuseyinova, MD; Clemens Boeckh,
PhD; Rainer Muche, PhD; Markus Kunze, MS; Dietrich Rothenbacher, MD, MPH; Gita
Pezeshki, PhD; Albrecht Hoffmeister, MD; Wolfgang Koenig, MD

Arch Intern Med. 2006;166:554-559.
Background  Chronic inflammation from any source is associated with increased
cardiovascular risk. Periodontitis is a possible trigger of chronic
inflammation. We investigated the possible association between periodontitis
and coronary heart disease (CHD), focusing on microbiological aspects.
Methods  A total of 789 subjects (263 patients with angiographically confirmed,
stable CHD and 526 population-based, age- and sex-matched controls without a
history of CHD) were included in the Coronary Event and Periodontal Disease
(CORODONT) study. Subgingival biofilm samples were analyzed for periodontal
pathogens Actinobacillus actinomycetemcomitans, Tannerella forsythensis,
Porphyromonas gingivalis, Prevotella intermedia, and Treponema denticola using
DNA-DNA hybridization. The need for periodontal treatment in each subject was
assessed using the Community Periodontal Index of Treatment Needs (CPITN). The
main outcome measures included total periodontal pathogen burden, number of the
various periodontal pathogens in the subgingival biofilm, and periodontal
treatment needs (according to the CPITN).

Results  In multivariable analyses, we found a statistically significant
association between the periodontal pathogen burden (log10 of the sum of all
pathogens) (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.34-2.74;
P<.001) or the number of A actinomycetemcomitans in periodontal pockets (log10)
(OR, 2.70; 95% CI, 1.79-4.07; P<.001) and the presence of CHD. In addition, a
statistically significant association between an increase in mean CPITN score
by 1 and the presence of CHD (OR, 1.67; 95% CI, 1.08-2.58; P = .02) was
observed.

Conclusions  Our findings suggest an association between periodontitis and
presence of CHD. Periodontal pathogen burden, and particularly infection with A
actinomycetemcomitans, may be of special importance.

Anders Holmlund, ­Gunnar Holm, ­Lars Lind. Severity of Periodontal Disease and Number of Remaining Teeth Are Related to the Prevalence of Myocardial Infarction and Hypertension in a Study Based on 4,254 Subjects. Journal of Periodontology 2006, Vol. 77, No. 7, Pages 1173-1178

Background: During the past 15 years, mounting evidence for the association between periodontal and cardiovascular disease has been presented in epidemiological studies. The aim of this study was to investigate how the severity of periodontal disease and number of remaining teeth relates to myocardial infarction (MI) and hypertension (HT).

Methods: Self-reported history of HT and MI was collected in 3,352 patients referred to the Department of Periodontology, Gävle County Hospital, and in 902 subjects randomly selected from the general population. Severity of periodontitis was estimated by a combination of the amount of bone loss around each tooth investigated from a full-mouth x-ray, the presence or absence of bleeding on probing (BOP), and involvement of furcations.

Results: The severity of periodontitis was significantly associated with HT (prevalence 16%; P <0.0005), even after adjustment for age, gender, number of teeth, and smoking in the total sample, and with MI (prevalence 1.7%, P <0.03) after above-mentioned adjustments, but in middle-aged (40 to 60 years) subjects only. The number of diseased periodontal pockets was related to HT only (P <0.0001), and this relationship remained after the above-mentioned adjustments. The number of teeth was associated with MI (P <0.03) even after correction for age, gender, and smoking but was not related to hypertension.

Conclusions: The severity of periodontal disease was related to HT independent of age but to the prevalence of MI in middle-aged subjects only. The number of diseased pockets was significantly related to HT only. On the other hand, the number of teeth was associated with the prevalence of MI independent of age but not to HT. These data support the view that oral health is related to cardiovascular disease in a dose-dependent manner.

First Study To Take Bacteria Directly From Patients’ Mouths Further Supports Possible Link Between Gum And Heart Disease

ScienceDaily (Feb. 27, 1998) — By taking bacteria samples directly from patients’ mouths and exposing the samples to human blood platelets, researchers at Temple Univeristy Schools of Dentistry and Medicine have further confirmed a possible link between periodontal bacteria and heart disease.

In recent weeks, a great deal of media attention has been focused on this possible relationship. In fact, since the early 1990s, preliminary studies at other universities have used laboratory strains of mouth bacteria and population data to show this possible link.

Temple’s study is the first to take a large number of dental plaque bacteria directly from the mouths of patients with severe periodontal disease and test their effect on blood platelets.

“Almost immediately after we exposed human blood platlets to the dental plaque bacteria, the platelets began to clump together,” says Dr. Eugene J. Whitaker, associate professor of Dentistry and lead investigator. “And, out of all the periodontal bacteria we tested, Porphyromanas gingivalis was the only one to cause this clumping, which is a key step in formation of bloodstream thrombi (blockage).”

Porphyromanas gingivalis is the most important bacterial cause of destructive gum diseases in adults. The Temple research findings further support and expand a possible link between periodontal disease and development of athrosclerotic heart disease, a condition resulting from plaque build-up and constriction of coronary heart arteries, and strokes affecting the brain.

“The importance of our findings is that at least 36 million American adults have some form of destructive periodontal disease, which leads to loosening and loss of teeth,” says Dr. Thomas E. Rams, a co-investigator and chairman of Temple’s Department of Periodontology. “Porphyromanas gingivalis is very frequently in dental plaque causing this disease. These people may be at increased risk of getting heart disease and strokes if Porphyromanas gingivalis from their mouth gets into the bloodstream and clumps platelets similar to what we see in the laboratory.”

Note the date is 1998!–Ed

New Research Finds Link Between Gum Disease, Acute Heart Attacks

ScienceDaily (Nov. 13, 2000) — CHAPEL HILL — Heart attack survivors who suffer advanced gum disease show significantly higher levels of a protein in their blood called C-reactive protein (CRP) than such patients without gum disease, new University of North Carolina at Chapel Hill research indicates.

The findings, presented Sunday (Nov. 12) during a news conference at the annual American Heart Association meeting in New Orleans, suggest that the presence of gum disease might increase the risk of a second heart attack in people with a history of heart disease.

“Not only did the heart attack patients with periodontal disease have higher levels of CRP than those without gum disease, but the CRP levels were directly related to the severity of the gum disease,” said Dr. Efthymios N. Deliargyris, an interventional cardiologist and a member of the Center for Oral and Systemic Diseases at UNC-CH. “The more severe the gum disease, the higher the CRP levels.”

Besides Deliargyris, also an instructor in medicine at the UNC-CH School of Medicine, study investigators were Drs. Steven Offenbacher, professor of periodontology and center director, James D. Beck, professor of dental ecology, both at the UNC-CH School of Dentistry, and Sidney C. Smith Jr., chief of cardiology and past president of the American Heart Association.

“We know a lot of risk factors for heart attacks, including high blood pressure, high cholesterol, diabetes and cigarette smoking, but all those combined only explain about two-thirds of heart attacks,” Deliargyris said. “Since about a third of people who suffer heart attacks don’t have those risk factors, there’s a wide search going on for other conditions that may contribute to increased risk.”

Studies at UNC-CH and elsewhere have linked periodontal disease — an advanced form of gingivitis — with increased risk of heart attacks, but it has been unclear what the two conditions have in common, the physician said.

“The one thing we know the two conditions share is that they tend to initiate an immune response, also called an inflammatory response, in the body,” he said. “The most common marker for this response is this C-reactive protein, which is considered predictive of future adverse events like heart attack.” To learn how common severe gum disease was in heart attack victims, the UNC-CH team conducted their pilot study of 38 heart attack patients and matched them with a comparable group of 38 other people without known heart disease. Researchers found a high percentage of the former had periodontal disease — 85 percent — as compared with only 29 percent of the controls.

“The most exciting finding was that among people with a heart attack, those with periodontal disease had much higher CRP levels than those with a heart attack but no periodontal disease,” Deliargyris said. “It seems that the presence of periodontal disease on top of a heart attack has a synergistic effect and a very accentuated CRP release.”

Despite its small size, the study findings are the first of their kind and potentially very important, he said.

“This gives us an insight into possible mechanisms underlying the association between gum disease and heart disease,” Deliargyris said. “Now we believe that patients with a heart attack and periodontal disease have an exaggerated inflammatory response with higher CRP levels that might put them at risk for future heart attacks. This work also raises the possibility that by treating severe gum disease in people with heart attacks, we might be able to reduce their CRP levels and their risk of another heart attack.”

Curr Pharm Des. 2007;13(36):3665-75.

Porphyromonas gingivalis mediated periodontal disease and atherosclerosis: disparate diseases with commonalities in pathogenesis through TLRs.

Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

Toll-like receptors (TLRs) are a group of pathogen-associated molecular pattern receptors, which play an important role in innate immune signaling in response to microbial infection. It has been demonstrated that TLRs are differentially up regulated in response to microbial infection and chronic inflammatory diseases such as atherosclerosis. Furthermore hyperlipidemic mice deficient in TLR2, TLR4, and MyD88 signaling exhibit diminished inflammatory responses and decreased atherosclerosis. Accumulating evidence has implicated specific infectious agents including the periodontal disease pathogen Porphyromonas gingivalis in the progression of atherosclerosis. Evidence in humans suggesting that periodontal infection predisposes to atherosclerosis is derived from studies demonstrating that the periodontal pathogen P. gingivalis resides in the wall of atherosclerotic vessels and seroepidemiological studies demonstrating an association between pathogen-specific IgG antibodies and atherosclerosis. We have established that the inflammatory signaling pathways that P. gingivalis utilizes is dependent on the cell type and this specificity clearly influences innate immune signaling in the context of local and distant chronic inflammation induced by this pathogen. We have demonstrated that P. gingivalis requires TLR2 to induce oral inflammatory bone lose in mice. Furthermore, we have demonstrated that P. gingivalis infection accelerates atherosclerosis in hyperlipidemic mice with an associated increase in expression of TLR2 and TLR4 in atherosclerotic lesions. Our recent work with P. gingivalis has demonstrated the effectiveness of specific intervention strategies (immunization) in the prevention of pathogen-accelerated atherosclerosis. Improved understanding of the mechanisms driving infection, and chronic inflammation during atherosclerosis may ultimately provide new targets for therapy.

1: Circulation. 2004 Jun 8;109(22):2801-6. Epub 2004 May 3.   Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. Gibson FC 3rd, Hong C, Chou HH, Yumoto H, Chen J, Lien E, Wong J, Genco CA.

Department of Medicine, Section of Infectious Diseases, Boston University Medical Center, Boston, Mass, USA.

BACKGROUND: Infectious diseases have emerged as potential risk factors for cardiovascular disease (CVD). Epidemiological studies support a connection between periodontal disease, a chronic inflammatory disease of the supporting tissues of the teeth, and CVD. METHODS AND RESULTS: To directly test the connection between periodontal disease and atherosclerosis, apoE-/- mice were orally challenged with the periodontal disease pathogen Porphyromonas gingivalis or an invasion-impaired P gingivalis fimbriae-deficient mutant (FimA-). Both wild-type P gingivalis and the FimA- mutant were detected in blood and aortic arch tissue of apoE-/- mice by PCR after challenge. ApoE-/- mice challenged with wild-type P gingivalis presented with increased atherosclerotic plaque and expressed the innate immune response markers Toll-like receptor (TLR)-2 and TLR-4 in aortic tissue. Despite detection of the FimA- mutant in the blood and in aortic arch tissue, apoE-/- mice challenged with the FimA- mutant did not present with periodontal disease, upregulation of TLRs, or accelerated atherosclerosis. Furthermore, we demonstrate that immunization to control P gingivalis-elicited periodontal disease concomitantly prevents P gingivalis-accelerated atherosclerosis. CONCLUSIONS: We conclude that invasive P gingivalis accelerates atherosclerosis.

——————–

QUESTIONS from Editor

Now, WHY use apoE deficient mice for this study?  Couldn’t it have been done with regular mice?

This is of some interest, since it also seems that there are 4 variations of apolipoprotein-E in humans.  And, particularly, men can have a greater likelihood of the variant that has few or no sulfhydryl groups on this enzyme.  The consequence is a higher likelihood of sensitivity to heavy metals such as Hg and the inability to clear them systemically.

Another interesting point is that the NON-invading type of P. ging–those poor critters without their fimbriae–didn’t seem to cause perio or atherosclerosis.  [And also note that the Sonicare toothbrush takes the fimbriae off bacteria.]

Finally, one last comment: PCR testing showed that P. ging got into the lining of the mouse aorta.    BUT–does this mean live, viable bugs did or just some of their DNA?

Should we be looking at atherosclerosis as an infective process or a reactive process? 

Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1433-9. Epub 2007 Mar 15. Links

Endotoxemia, immune response to periodontal pathogens, and systemic inflammation associate with incident cardiovascular disease events.

Institute of Dentistry, University of Helsinki, Haartmaninkatu 8, PO Box 63, FI-00014 Helsinki, Finland. [email protected]

OBJECTIVE: In periodontitis, overgrowth of gram-negative bacteria may cause endotoxemia and systemic inflammation leading to cardiovascular diseases (CVD). We investigated in a prospective study the associations of serum endotoxin, antibodies to periodontal pathogens, and inflammation markers with the risk of incident CVD. METHODS AND RESULTS: The FINRISK 1992 cohort of 6051 individuals was followed up for 10 years. We examined 185 incident CVD events and a control cohort of 320 individuals using a prospective case-cohort design. High antibody response to periodontal pathogens independently predicted incident CVD events with hazard ratios (HR, quartile 4 versus quartiles 1 to 3, 95% CI) of 1.87 (1.13 to 3.08). The subjects with a high antibody response and high CRP or interleukin (IL)-6 had multivariate-adjusted HRs of 3.01 (1.27 to 7.09) and 3.11 (1.42 to 6.83) compared with low-responders, respectively. The corresponding HRs for high endotoxin concentration were 1.82 (1.22 to 2.73, alone), 3.92 (1.99 to 7.74, with CRP), 3.54 (1.78 to 7.03, with IL-6), and 2.26 (1.13 to 4.52, with tumor necrosis factor (TNF)-alpha) after adjusting for age and gender. These associations were abolished after adjusting for serum lipids. High endotoxin/HDL ratio, however, had a multivariate-adjusted HR of 1.92 (1.19 to 3.08) for CVD events. CONCLUSIONS: Our results suggest that the exposure to periodontal pathogens or endotoxin induces systemic inflammation leading to increased risk for CVD.

The question, of course is whether that relationship is causative or simply the evidence of some other underlying condition or defect.–Ed

High serum antibody levels to Porphyromonas gingivalis predict myocardial infarction.
Pussinen PJ, Alfthan G, Tuomilehto J, Asikainen S, Jousilahti P.

BACKGROUND: An association between coronary heart disease (CHD) and clinically diagnosed periodontitis has been found in several epidemiological studies. However, seroepidemiologic evidence based on prospective data on this association is totally lacking. DESIGN: The aim of the study was to investigate serum antibodies to major periodontal pathogens for their prediction of myocardial infarction (MI) in men free of CHD at baseline. METHODS: Cases and controls were ascertained from a random population sample of 4255 men aged 30 to 59 years at baseline. The study cases included 63 men with nonfatal MI or coronary death within the follow-up time of 10 years. Age-matched control subjects (n=63) were randomly chosen from the same cohort. Serum antibody levels to two major periodontopathogenic bacteria, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined. RESULTS: There was no significant association between the risk for MI and IgG- or IgA-class antibody levels to A. actinomycetemcomitans or IgG-class antibody levels to P. gingivalis. However, a high P. gingivalis IgA-class antibody level predicted MI independently of classical cardiovascular risk factors. The risk for MI increased by increasing quartiles of antibody levels (P for the trend 0.021). Compared with the first quartile, the multivariate odds ratios of MI in the second, third and fourth quartiles were 2.47 (95% CI 0.75-8.11), 3.30 (1.03-10.58) and 3.99 (1.22-13.10), respectively. CONCLUSION: The study provides serological evidence that an infection caused by the periodontal pathogen, P. gingivalis, increases the risk for MI.

Int J Cardiol. 2007 Oct 31;122(1):79-81. Epub 2007 Jan 17

Elevated IgG titers to periodontal pathogens related to Buerger disease.

BACKGROUND: Periodontal pathogens were frequently detected in the occluded arteries of Buerger disease patients, hence we hypothesized that the infection from periodontal pathogens may be associated with Buerger disease. METHODS: We investigated periodontal status using various clinical parameters and serum IgG antibody levels against T. denticola, P. gingivalis, A. actinomycetemcomitans and P. intermedia in nineteen Buerger disease patients and fifteen control subjects. The results were statistically analyzed. RESULTS: The prevalence of periodontitis and the percentages of probing sites with PD> or =4 mm and CAL> or =4 mm were significantly higher in the patient group (P<0.001, P=0.016, and P<0.001, respectively). Patients had significantly higher serum IgG titers against T. denticola, P. gingivalis and A. actinomycetemcomitans (P=0.002, P=0.039, and P=0.011, respectively). CONCLUSIONS: This study provides evidence for possible implications of periodontitis in Buerger disease.

C-reactive protein associated with periodontitis in a Thai population.

Department of Community Dentistry, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.

Aim: C-reactive protein (CRP) has been implicated as a possible mediator of the association between periodontitis and several systemic diseases. Previous studies suggest an association between increased CRP levels and periodontitis predominantly in Caucasians. This study evaluated the associations of chronic periodontitis and Porphyromonas gingivalis with CRP in systemically healthy Thai adults. Material and Methods: Serum high-sensitivity CRP was measured in 21 generalized periodontitis, 62 localized periodontitis, and 38 periodontally healthy control subjects. P. gingivalis in subgingival plaque samples was analyzed by polymerase chain reaction. Results: Overall, these subjects had a median CRP level lower than that reported in the western populations. Subjects with generalized periodontitis and localized periodontitis had higher median CRP levels than controls (1.78 and 0.65 mg/l versus 0.25 mg/l, p<0.001). Multivariate linear regression showed that log CRP levels were increased in subjects with generalized periodontitis (p<0.01) and localized periodontitis (p=0.03) compared with the controls, adjusted for age, body mass index and smoking. Presence of P. gingivalis was also independently associated with elevated log CRP levels (p<0.001). Conclusion: Periodontitis and subgingival P. gingivalis are associated with increased CRP levels. These findings suggest that periodontal infection may contribute to systemic inflammatory burden in otherwise healthy individuals.

J Med Microbiol 54 (2005), 93-96; DOI: 10.1099/jmm.0.45845-0
© 2005 Society for General Microbiology
ISSN 0022-2615

Molecular detection of Treponema denticola and Porphyromonas gingivalis in carotid and aortic atheromatous plaques by FISH: report of two cases

Deep Periodontal Pockets Increase Risk for Electrocardiographic Abnormalities

CHICAGO – June 22, 2004 – People with deep periodontal pockets had an increased risk for electrocardiographic abnormalities (ECG) according to a recent study printed in this month’s issue of the Journal of Periodontology Study Abstract *

Japanese researchers examined general and oral health of 1,111 people and included 957 people who had greater or equal to 10 teeth and did not have a medical history of cardiovascular disease were included.

“We found that people with deep periodontal pockets with a mean value greater than two millimeters had an increased risk for ECG abnormalities compared with people who had pockets with a mean value less than two millimeters. And, people with severe attachment loss with a mean value greater than 2.5 millimeters had a significant risk for ECG abnormalities.” said Dr. Yoshihiro Shimazaki, Department of Preventive Dentistry, Kyushu University Faculty of Dental Science, Japan. “Considering these results, the relationship between periodontitis and ECG abnormalities observed in this study suggests a relationship between periodontitis and cardiovascular disease.”

Periodontitis is a chronic inflammatory bacterial infection. Past studies report that periodontitis results in higher systemic levels of C-reactive protein (CRP), interleukin-6 and neutrophils suggesting that elevated levels of these inflammatory substances cause inflammatory changes to atherosclerotic lesions, which increases the risk of cardiac events.

“This study adds to the growing body of evidence that links periodontitis to cardiovascular disease,” said Dr. Michael P. Rethman, DDS, MS, and president of the American Academy of Periodontology. “In order to examine the degree of cardiovascular risk from periodontitis compared with other risk factors, cohort studies are required. For example, because problematical ECG results are a widely appreciated risk factor for cardiovascular disease, it could be clinically valuable to know the effects of periodontal treatment on ECG exams.”

As ECG examinations cause no discomfort and take only a few minutes, it is widely used to screen for heart disease in health examinations. ECG abnormalities are significantly related to subsequent death from coronary heart disease and one of the most sensitive predictors of fatal coronary heart disease.

Comprehensive periodontal therapy is provided by dental specialists – known as periodontists – who are graduates of three-year residencies that they undertake after graduating from dental school. General dentists and dental hygienists can also provide more limited periodontal care.

from American Academy of Periodontology http://www.perio.org/consumer/ecg.htm

New Study Confirms Periodontal Disease Linked to Heart Disease

CHICAGO – February 7, 2002 – A newly published study in the Journal of Periodontology confirms recent findings that people with periodontal disease are at a greater risk of systemic diseases such as cardiovascular disease. Study Abstract *

Researchers found diseased gums released significantly higher levels of bacterial pro-inflammatory components, such as endotoxins, into the bloodstream in patients with severe periodontal disease compared to healthy patients. As a result, these harmful bacterial components in the blood could travel to other organs in the body, such as the heart, and cause harm.

The study is in line with recent findings by the University of Buffalo where researchers suggest periodontal disease may cause oral bacterial components to enter the bloodstream and trigger the liver to make C-reactive proteins, which are a predictor for increased risk for cardiovascular disease.

“We found the mouth can be a major source of chronic or permanent release of toxic bacterial components in the bloodstream during normal oral functions,” said Dr. E.H. Rompen, director of the study. “This could be the missing link explaining the abnormally high blood levels of some inflammatory markers or endotoxemia observed in patients with periodontal disease.”

Researchers studied 67 patients of whom 42 were diagnosed with moderate to severe periodontitis and the remaining 25 patients were healthy individuals who had never received periodontal treatment. Blood samples were taken before and after patients lightly chewed chewing gum 50 times on each side of their jaw. Researchers found the number of patients with endotoxemia rose from six percent before chewing to 24 percent after chewing. Additionally, those with severe periodontal disease had approximately four times more harmful bacterial products in their blood than those with moderate or no periodontal disease.

“While this clinical study supports earlier findings, there is still much research to be done to understand the link between periodontal disease and systemic diseases, such as cardiovascular, and difficult-to-control diabetes,” said Kenneth Bueltmann, D.D.S., president of the American Academy of Periodontology (AAP). “This data clearly stresses the importance of regular dental checkups to ensure a healthy, diseased-free mouth.”

Periodontal diseases are serious bacterial infections that destroy the attachment fibers and supporting bone that hold your teeth in your mouth. When this happens, gums separate from the teeth, forming pockets that fill with plaque and even more infection. As the disease progresses, these pockets deepen even further, more gum tissue and bone are destroyed and the teeth eventually become loose. Approximately 15 percent of adults between 21 and 50 years old and 30 percent of adults over 50 have the disease.

Periodontal Infections and Coronary Heart Disease

from Archives of Internal Medicine Vol. 166 No. 5, March 13, 200

Role of Periodontal Bacteria and Importance of Total Pathogen Burden in the Coronary Event and Periodontal Disease (CORODONT) Study

Axel Spahr, DDS; Elena Klein, DDS; Natalie Khuseyinova, MD; Clemens Boeckh, PhD; Rainer Muche, PhD; Markus Kunze, MS; Dietrich Rothenbacher, MD, MPH; Gita Pezeshki, PhD; Albrecht Hoffmeister, MD; Wolfgang Koenig, MD

Arch Intern Med. 2006;166:554-559.

Background  Chronic inflammation from any source is associated with increased cardiovascular risk. Periodontitis is a possible trigger of chronic inflammation. We investigated the possible association between periodontitis and coronary heart disease (CHD), focusing on microbiological aspects.

Methods  A total of 789 subjects (263 patients with angiographically confirmed, stable CHD and 526 population-based, age- and sex-matched controls without a history of CHD) were included in the Coronary Event and Periodontal Disease (CORODONT) study. Subgingival biofilm samples were analyzed for periodontal pathogens Actinobacillus actinomycetemcomitans, Tannerella forsythensis, Porphyromonas gingivalis, Prevotella intermedia, and Treponema denticola using DNA-DNA hybridization. The need for periodontal treatment in each subject was assessed using the Community Periodontal Index of Treatment Needs (CPITN). The main outcome measures included total periodontal pathogen burden, number of the various periodontal pathogens in the subgingival biofilm, and periodontal treatment needs (according to the CPITN).

Results  In multivariable analyses, we found a statistically significant association between the periodontal pathogen burden (log10 of the sum of all pathogens) (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.34-2.74; P<.001) or the number of A actinomycetemcomitans in periodontal pockets (log10) (OR, 2.70; 95% CI, 1.79-4.07; P<.001) and the presence of CHD. In addition, a statistically significant association between an increase in mean CPITN score by 1 and the presence of CHD (OR, 1.67; 95% CI, 1.08-2.58; P = .02) was observed.

Conclusions  Our findings suggest an association between periodontitis and presence of CHD. Periodontal pathogen burden, and particularly infection with A actinomycetemcomitans, may be of special importance.

Atherosclerosis and Lipoproteins

Endotoxemia, Immune Response to Periodontal Pathogens, and Systemic Inflammation Associate With Incident Cardiovascular Disease Events
Pirkko J. Pussinen; Karolina Tuomisto; Pekka Jousilahti; Aki S. Havulinna; Jouko Sundvall; Veikko Salomaa

From the Institute of Dentistry (P.J.P.), University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital; the Department of Epidemiology and Health Promotion (K.T., P.J., A.S.H., V.S.), National Public Health Institute, Helsinki; the School of Public Health (P.J.), University of Tampere; and the Department of Health and Functional Capacity (J.S.), National Public Health Institute, Helsinki, Finland.
Correspondence to Pirkko Pussinen, Institute of Dentistry, University of Helsinki, Haartmaninkatu 8, PO Box 63, FI-00014 Helsinki, Finland. E-mail [email protected]
Objective— In periodontitis, overgrowth of Gram-negative bacteria may cause endotoxemia and systemic inflammation leading to cardiovascular diseases (CVD). We investigated in a prospective study the associations of serum endotoxin, antibodies to periodontal pathogens, and inflammation markers with the risk of incident CVD.
Methods and Results— The FINRISK 1992 cohort of 6051 individuals was followed up for 10 years. We examined 185 incident CVD events and a control cohort of 320 individuals using a prospective case–cohort design. High antibody response to periodontal pathogens independently predicted incident CVD events with hazard ratios (HR, quartile 4 versus quartiles 1 to 3, 95% CI) of 1.87 (1.13 to 3.08). The subjects with a high antibody response and high CRP or interleukin (IL)-6 had multivariate-adjusted HRs of 3.01 (1.27 to 7.09) and 3.11 (1.42 to 6.83) compared with low-responders, respectively. The corresponding HRs for high endotoxin concentration were 1.82 (1.22 to 2.73, alone), 3.92 (1.99 to 7.74, with CRP), 3.54 (1.78 to 7.03, with IL-6), and 2.26 (1.13 to 4.52, with tumor necrosis factor (TNF)-) after adjusting for age and gender. These associations were abolished after adjusting for serum lipids. High endotoxin/HDL ratio, however, had a multivariate-adjusted HR of 1.92 (1.19 to 3.08) for CVD events.

Conclusions— Our results suggest that the exposure to periodontal pathogens or endotoxin induces systemic inflammation leading to increased risk for CVD.
We investigated the connection between serum inflammation markers, antibody levels to major periodontal pathogens, endotoxin concentration, and CVD events in a prospective case–cohort study. Our results suggest that endotoxemia or systemic immune response to periodontal pathogens together with high concentrations of inflammation markers indicate a high risk of incident CVD.

Inflammation, heat shock proteins and periodontal pathogens in atherosclerosis: an immunohistologic study.

Oral Biology and Pathology, School of Dentistry, The University of Queensland, Brisbane, Australia. [email protected]

BACKGROUND: Inflammation is a significant component of atherosclerosis lesions. Bacteria, including periodontopathogens, have been demonstrated in atherosclerotic plaques and cross-reactivity of the immune response to bacterial GroEL with human heat shock protein 60 has been suggested as a link between infections and atherosclerosis. METHODS: In this study, the nature of the inflammatory infiltrate and the presence of human heat shock protein 60 and GroEL were examined in 31 carotid endarterectomy specimens. Additionally, monoclonal antibodies were used to detect the presence of six bacteria, including those implicated in periodontal disease. RESULTS: The inflammatory cell infiltrate of the lesions was dominated by CD14(+) macrophages and CD4(+) T cells. Most cells of the infiltrate as well as the endothelium were HLA-DR(+), indicating activation; however, there was an absence of CD25 expression, demonstrating that the activated T cells were not proliferating. Few CD1a(+) and CD83(+) cells were noted. Human heat shock protein 60 expression was evident on endothelial cells and cells with the appearance of smooth muscle cells and lymphocytes. GroEL and bacteria were detected within intimal cells. Chlamydia pneumoniae, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia, Prevotella intermedia, and Actinobacillus actinomycetemcomitans were found in 21%, 52%, 34%, 34%, 41%, and 17% of arteries, respectively. CONCLUSION: These results give evidence for a specific immune response associated with atherosclerosis. Whether bacteria initiate the observed inflammation in atherosclerotic lesions is not clear; however, the present study shows that maintenance of inflammation may be enhanced by the presence of periodontopathic bacteria.

PMID: 16842503