I t has long been theorized that there is a relationship between periodontal disease and cardiovascular disease. Only in the last decade, however, has science made progress in identifying what dentists have long observed; that there are cardiac implications in periodontal disease patients. As science discovers new ways to identify the specific disease process, and pathogens, the dental profession discovers new ways to manage the disease from a medical approach. The dental practitioner will be challenged with a new paradigm in the next decade and well into the new millennium. Therefore, this report is submitted to update the provider on the subject.
In 1989, Dr. Kimmo Mattila and a group of Finnish physicians published two papers definitively linking dental health and the heart. Their study was based on the clinical impression that chronic dental infections are common among patients with acute myocardial infarction. Their observations indicated that dental caries or periodontal disease, or both, shared several common etiological factors. The so-called classic risk factors of coronary heart disease did not explain all the clinical and epidemiological features of the disease and in 1993, Mattila presented his own paper citing a mechanism for the effect of bacteria on the cells taking part in the pathogenesis of atherosclerosis and arterial thrombosis.
During the 1990’s, there has been a considerable amount of study and published literature on this subject based on the findings of Mattila. Two essential articles by Dr Walter Loesche, the father of the Specific Plaque Hypothesis , are required reading for the dental professional (Loesche 1995 and Loesche & others 1998). His 1995 article presented the findings of the National Health and Nutrition Examination Study that confirmed the findings of the Finnish researchers. Loesche felt that the most noteworthy finding in that study was that periodontal disease and poor oral hygiene are stronger indicators of risk of total mortality than of coronary heart disease. Individuals with periodontal disease were reported to be 1.7 times more likely to develop coronary heart disease and 2.6 times more likely to die of cardiovascular disease than those without periodontal disease. He found these results so incredible that he offered a hypothesis to explain the association between periodontal disease and coronary heart disease. He implicated specific bacterial strains in the oral plaque that could enter the blood stream and cause subsequent vascular pathology. It was not until 1998, however, that Loesche and a group of investigators from the University of Michigan presented a paper confirming that a statistically significant association exists between a diagnosis of coronary heart disease and certain oral health parameters. In addition to reviewing pertinent literature to date, they conducted a study that utilized elderly U.S. Veteran subjects to assess the relationship between dental disease and coronary heart disease. They identified risk indicators for coronary heart disease, but could not label them as risk factors because the specific population did not represent the general population. Their results, however, confirmed those of previous studies conducted with younger subjects.
To amplify, the etiology of periodontal disease is, for the most part, still hypothetical. The traditional model (Grant & others 1988) of periodontal destruction implicates plaque. There are two microbial components that are toxic to periodontal tissues. Endotoxin, or lipopolysaccharides, that are produced by gram-negative organisms and the mucopeptide complex of gram-positive bacteria. Injected endotoxin into experimental animals results in fever, necrotic reactions, diarrhea, and even death. Endotoxins are multipotential initiators of gingival inflammation and can destroy tissue directly or indirectly by the process of chemotaxis where neutrophils accumulate in the gingival tissues as the host response to the endotoxin. They release lysosomal enzymes in defense, but also have the capacity to destroy tissue. The neutrophils are followed by monocytes, that release inflammatory mediators, and macrophages. Different forms of periodontal disease have specific microbial etiologies.
Although the inflammatory reaction of the gingiva exhibits the same characteristic pattern as inflammation elsewhere in the body, the periodontium possesses certain unique features.
One of the studies Loesche cites as significant is a 1996 paper by Dr. James Beck and others from the University of North Carolina and the Department of Veterans Affairs. Their central hypothesis is that periodontal diseases represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. They state that the cardiovascular implications of periodontal disease may be due to an underlying inflammatory response trait, which places the patient at high risk for both. Of the 17 characteristics he analyzed for periodontitis, he found that 9 of them were characteristics of heart disease. The associated risk factors are age, education, gender, finances, tobacco use, alcohol, hypertension, stress, and social isolation. These common risk factors indicate that periodontal diseases and heart disease may share a common etiologic pathway and he proposed a model to explain the biological mechanisms underlying the observed association.
In Beck’s model, the host response to bacterial challenge is an abnormally high inflammatory reaction. Patients with certain forms of periodontal disease possess a specific blood monocyte phenotype (MØ+). MØ+ individuals secrete 3-10 times more mediators in response to lipopolysaccharides than normal phenotype individuals. The MØ+ phenotype is found in early-onset periodontitis (pre-pubertal, juvenile, and rapidly progressive), refractory periodontitis, and those with insulin-dependent diabetes mellitus.
Periodontal disease, once established, results in a chronic, systemic vascular challenge with bacterial lipopolysaccharides (endotoxin) and host-derived inflammatory cytokines that directly contribute to the pathogenesis of atherosclerosis and thromboembolic events. The periodontal pocket is lined with ulcerated epithelium that permits direct bacterial contact with the connective tissue and the inflammatory cell infiltrate. Within the periodontium, the monocyte responds to the bacterial lipopolysaccharide by secreting pro-inflammatory mediators (prostaglandins and interleukins). These mediators have damaging effects on the periodontium by causing vasodilation and increased vasopermeability, inflammatory cell recruitment, connective tissue degradation, and bone destruction. Intravascular infusion of lipopolysaccharides upregulates the expression of endothelial adhesion molecules, triggers the release of the pro-inflammatory mediators (including tumor necrosis factor), initiates platelet aggregation and adhesion, and promotes the formation of lipid-laden foam cells and the deposition of cholesterol within the vascular endothelium and smooth muscle. Therefore, bacterial endotoxin can start an impressive cascade of inflammatory cytokines capable of producing vascular and coagulation complications associated with atherosclerosis and coronary heart disease. Lipopolysaccharides can also elicit a specific immunologic response.
The levels of inflammatory mediators present in the gingival crevicular fluid provide a direct assessment of the underlying host inflammatory response capability. Anti-inflammatory agents, such as the non-steroidal flurbiprofen , block the synthesis or activity of these pro-inflammatory mediators and have been shown to reduce the severity of periodontal disease. The mechanism of action appears to be similar to that expressed in the treatment of arthritis where bacterial products that bind to stimulate monocytes and osteoblasts to secrete cytokines and eicosanoids, which can then induce the recruitment and activation of macrophages and osteoclasts and the release of collagenases. Both periodontal disease and arthritis respond to treatment with non-steroidal-anti-inflammatory medications (Scannapieco 1998).
More than 400 species of bacteria create a complex microbial ecological system in the form of a biofilm. Early colonizers of this biofilm are the streptococci that help initiate dental caries. Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola are the significant colonizers associated with periodontal disease. Identifying specific bacteria responsible for the association between periodontal and cardiovascular disease is the challenge of research today. In Dr. Harold Slavkin’s observations, Director of the National Institute of Dental and Craniofacial Research (1999), S. sanguis and P. ginivalis have been shown to induce platelets to aggregate in vitro, providing a model of thrombosis. Aggregation of platelets requires a surface protein found on both of these microbes called platelet aggregation-associated protein, or PAAP. In more than 60% of adults, dental plaque harbors PAAP and S. sanguis microbes.
Commensal bacteria may behave as opportunistic pathogens in a compromised host. Upon colonization of the subgingival plaque, pathogenic organisms like A. Actinomycetemcomitans and P. gingivalis invade and lyse mucosal epithelial cells and digest a pathway into connective tissues. This stimulates periodontal inflammation and platelets are encountered in the gingival circulation. The relatively harmless streptococci (S. sanguis) enter the blood stream and can cause a transient bacteremia. This can occur for years in patients with chronic oral infections such as periodontal disease. According to Herzberg & Meyer (1996), bacteria have been found in the blood following toothbrushing (40%), tooth extraction (60%), and periodontal surgery (88%). In their study, they examined the effects of the oral flora on platelets. S. sanguis has been shown to induce human and rabbit platelet aggregation in-vitro. Their study centered on proving the hypothesis that the same was true in-vivo. Using experimental rabbits, they induced platelet aggregation with infusion of S. sanguis. This resulted in changes in electrocardiograms, blood pressure, heart rate, and cardiac contractility. The data was consistent with a thrombogenic role for S. sanguis in cardiovascular disease. P. gingivalis has been shown to induce the same effects as S. sanguis. They deduced that in the presence of classical risk factors, bacteria with thrombogenic potential may contribute to the increased risk of myocardial infarction in the presence of periodontitis.
In most cases, thrombotic occlusion of a coronary artery immediately precedes myocardial infarction. The known major risk factors of MI are family history, age, social class, smoking, serum lipid concentrations, diabetes, and hypertension. These are known to contribute to atherosclerosis, but the direct trigger(s) of coronary artery thrombosis is not known. As reported by Mattila (1993), these risk factors only account for one-half to two-thirds of the clinical epidemiological features of coronary heart disease. Periodontitis, as we have seen, is now suggested as an additional risk factor. A review of the studies completed to date provides evidence that there is a link between coronary heart disease and dental health. The fact that vascular inflammation occurs in the apparent absence of infection has lead several investigators to search for an infection of unknown origin in atherosclerotic patients. Dental diseases are at the forefront of that investigation and have prompted the dental profession to publish position papers on the subject.
The American Academy of Periodontology (AAP), Research, Science, and Therapy Committee published a position paper in 1998 on the potential risk of periodontal disease for systemic diseases. In it, they state that a number of systemic diseases and conditions are risk factors for periodontal disease. These include diabetes mellitus, neutrophil disorders, osteopenia, and stress. They note that the classical risk factors of cardiovascular disease, including hypertension, hypercholesterolenemia, and cigarette smoking can only account for one-half to two-thirds of the factors in the incidence of cardiovascular disease. The major rationale for the treatment of periodontal disease is to prevent progression of the disease and to preserve the dentition. In the future, an additional rationale for periodontal therapy may be to prevent untoward effects on systemic health. Their opinion is that dental medicine must become more integrated with general medicine.
In 1996, the same committee of the AAP published an informational paper on periodontal management of patients with cardiovascular diseases. In this paper, more common cardiovascular disorders are discussed and dental management considerations are described. Management is predicated on obtaining a thorough medical history; conducting a physical examination to identify any physical signs and symptoms of cardiac dysfunction; evaluating vital signs when appropriate, including blood pressure, pulse rate, and respiratory function; and obtaining medical consultation when indicated.
The dental practitioner should be aware of the risk factors associated with cardiovascular diseases, as well as the warning signs of heart attack. The American Heart Association (AHA) has identified several factors that increase the risk of heart disease. They are divided into risk categories. Major risk factors are those that medical research has shown to be definitely associated with a significant increase in cardiovascular disease. They include factors that cannot be controlled like age, sex, and heredity. Factors that can be controlled to lower the risk of cardiovascular disease are tobacco use, high blood cholesterol levels, high blood pressure, physical inactivity, obesity, and diabetes mellitus. The AHA cites stress and socioeconomic status as additional factors. There is no mention of periodontal disease by the AHA as of the date of this report.
From a military standpoint, the Oral Disease Risk Management Protocol was distributed in July 1999. Though the bulk of the instruction is targeted at caries risk management, the military provider should pay attention to the periodontal protocol as well. Specifically, the directive associates periodontal disease with several systemic conditions. Though cardiovascular disease is not one of them, the literature reviewed here provides ample evidence that it should be included along with auto-immune disease, cancer chemotherapy, transplant surgery, and diabetes mellitus. The American Heart Association updated its recommendations for the prevention of bacterial endocarditis in 1997. The dental practitioner should be well aware of the subacute bacterial endocarditis prophylaxis regimen, but it is not included in this report. Periodontal infection cannot be controlled by debridement alone.
The concept of periodontal therapeutics has advanced so drastically in the last decade that the most recent World Workshop in Periodontics and European Workshops were principally devoted to dental therapeutics. The findings concluded that periodontal infection cannot be controlled by debridement alone. Some of the recommendations from these workshops are highlighted here for information. From the second European Workshop, the following is of interest to the general practitioner: Adjunctive systemic antibiotics are recommended for P. gingivalis and A. actinomycetemcomitans associated with early onset periodontitis, including juvenile periodontitis. Recommended antibiotics include tetracycline, metronidazole, and a combination of metronidazole with amoxycillin. Other patients to benefit from systemic antibiotics include those with refractory periodontitis, abscess, and necrotizing ulcerative periodontitis. Antibiotics and some antiseptics are recommended for local adjunctive use, especially in non-responding sites. Commercially available toothpastes with surfactants such as triclosan and chlorhexidine are effective and suitable vehicles for anti-plaque and anti-gingivitis agents.
The 1996 World Workshop in Periodontics was directed to improve clinical decision making using an evidenced-based approach. Relevant conclusions to this paper are summarized below: There is evidence for adjunctive benefits of sustained release tetracycline, doxycycline, minocycline and metronidazole; chlorhexidine, stannous fluoride, methylene blue and ofloxacin. Systemic antibiotics are acceptable only for early onset forms of periodontitis and refractory periodontitis. Promising adjunctive systems specified included; subgingival irrigation with high concentrations of anti-microbials, topical or systemic applications of non-steroidal-anti-inflammatory agents, low dose doxycycline to modify host response.
Non-surgical treatment of periodontal disease generally includes; mechanical therapy, pharmacotherapeutics, environmental control, and maintenance. It is important for the provider to identify the causative agent (bacteria) and its susceptibility to proposed adjunctive therapy prior to treatment. Culture and sensitivity testing and DNA analysis are tools very useful to the practitioner with improved methods. Periopathogens can be collected using an endodontic paperpoint dipped in the sulcus. This is the best method for obtaining information on antibiotic sensitivity. The composition of the gingival crevicular fluid can also be analyzed for detection of disease activity. DNA testing is the best source for culture identification, but does not provide antibiotic sensitivity.
With the increased interest in periodontal pharmacotherapeutics, the Federal Drug Administration recently approved three new therapies for the treatment of periodontal disease (Slavkin 1999).
Periostat : In patients with periodontitis, the body overproduces the enzyme collagenase that breaks down collagen, the structural basis of periodontal tissues. Periostat (doxycycline hyclate) capsules suppress collagenase protecting connective tissue from destruction. It is the first drug that specifically inhibits the host inflammatory response.
Atridox : An antibiotic gel that is administered with a syringe and blunt canula to infected periodontal pockets. Atridox (10% doxycycline hyclate) suppresses collagenase at a sustained rate for up to one week. Unlike Periostat, it can be used as a stand-alone therapy.
PerioChip : It is a biodegradable chip soaked with chlorhexidine, a broad-spectrum antibiotic that destroys the bacterial cell membrane and lyses the cell. PerioChip (Chlorhexidine digluconate) is placed directly into the periodontal pocket.
To review, subjects with high levels of substances related to inflammation are at increased risk of heart attack. The theory is that periodontal inflammation works to increase plaque buildup in the vasculature and increase risk of cardiovascular disease. Suggested mechanisms have periodontal bacteria producing lipopolysaccharides triggering potentially harmful mediators, both of which have been implicated in cardiovascular disease. Anti-inflammatory agents may provide some assistance in preventing heart disease (Meskin 1998).
Periodontics, as well as the dental profession as a whole, has seen a shift from surgical to non-surgical approaches based on medicine. The mechanical/surgical paradigm of practice will be converted to a pharmacological/regenerative paradigm. It is important to control the oral microflora for systemic reasons, based on the increasingly strong association now established between focal infection of oral origin, specifically periodontal, and a range of systemic diseases, including coronary heart disease. In a 1998 editorial by Dr. Meskin in the JADA, he warns the dental practitioner to get ready, because the word is out that research has identified periodontal disease as a major risk factor for cardiovascular disease. In short, the dentist is about to become a doctor and our ability to diagnose must improve. G. V. Black, in 1908, feared that dentists would become mechanics only and divorce themselves from the study of pathology. We can confidently expect future diagnostic tools to be organic, instead of metallic.
Cardiac Implications Of Periodontal diseases
CARDIAC IMPLICATIONS OF PERIODONTAL DISEASE dr shabeel pn
WHERE IT ALL STARTED <ul><li>MATTILA & OTHERS (1989) </li></ul><ul><ul><li>First to link dental health and the heart </li></ul></ul><ul><ul><li>Myocardial infarction patients </li></ul></ul><ul><ul><li>Caries, Periodontal Disease, or both? </li></ul></ul><ul><ul><li>Classic risk factors? </li></ul></ul><ul><li>MATTILA (1993) </li></ul><ul><ul><li>Pathogenic mechanism </li></ul></ul>
THANK YOU DR CHOW! <ul><li>JADA EDITORIAL (1998) </li></ul><ul><ul><li>“Research has identified periodontal disease as a major risk factor for cardiovascular disease and stroke.” </li></ul></ul><ul><ul><li>“Practitioners, get ready!” </li></ul></ul><ul><li>DR CHOW </li></ul><ul><ul><li>“I really want to know more.” </li></ul></ul>
LOESCHE <ul><li>1995 </li></ul><ul><li>NHANES Study </li></ul><ul><li>PD 1.7 X CHD </li></ul><ul><li>PD 2.6 X Dead </li></ul><ul><li>Hypothesis </li></ul><ul><li>1998 </li></ul><ul><li>Review of literature </li></ul><ul><li>U.S. Veterans </li></ul><ul><li>Statistically significant “association” </li></ul><ul><li>Risk indicators </li></ul><ul><li>S. sanguis </li></ul>
PATHOGENISIS REVIEW <ul><li>Pathogenesis is still hypothetical </li></ul><ul><li>Bacteria produce destructive toxins </li></ul><ul><ul><li>gram negative = lipopolysaccharide </li></ul></ul><ul><ul><li>gram positive = mucopeptide complex </li></ul></ul><ul><li>Toxins attract White Blood Cells </li></ul><ul><li>Accumulation is inflammation </li></ul><ul><li>Inflammation is destructive as well </li></ul>
PERIODONTIUM <ul><li>The soft tissue is in intimate contact with the tooth and plaque. </li></ul><ul><li>The junctional epithelium is non-keratinized with exposed intercellular spaces. </li></ul><ul><li>The tissue is highly vascularized and plaque products have access to it. </li></ul>
PERIODONTIUM <ul><li>The plaque products provoke increased permeability and exudation. </li></ul><ul><li>Inflammatory components and mediators are present in the gingival crevicular fluid. </li></ul><ul><li>Periodontal disease appears to involve preferential diffusion through the junctional epithelium. </li></ul>
BECK <ul><li>Periodontal disease represents a previously unrecognized risk factor for atherosclerosis and thromboembolic events. </li></ul><ul><li>Common risk factors </li></ul><ul><li>Common etiologic pathway </li></ul><ul><li>Common mechanism </li></ul>
BLOOD MONOCYTE PHENOTYPE <ul><li>MØ+ phenotype </li></ul><ul><li>Common inflammatory response trait </li></ul><ul><li>Abnormally high inflammatory reaction </li></ul><ul><li>Early-onset and Refractory Periodontitis </li></ul><ul><li>Insulin-dependent Diabetes Mellitus </li></ul><ul><li>Cascade of action </li></ul>
AAP <ul><li>1998 Position Paper </li></ul><ul><li>Risky patients for PD </li></ul><ul><ul><li>IDDM, Neutropenia, osteopenia, & stress </li></ul></ul><ul><li>Risky patients for CHD </li></ul><ul><ul><li>HTN, Hypercholesterol, smokers, etc. </li></ul></ul><ul><li>Perio patients risky for CHD? </li></ul><ul><li>New rationale for periodontal therapy? </li></ul>
AAP <ul><li>1996 Informational Paper </li></ul><ul><li>Periodontal Management of Patients with Cardiovascular Disease </li></ul><ul><li>Recommendations: </li></ul><ul><ul><li>Medical History </li></ul></ul><ul><ul><li>Physical Examination </li></ul></ul><ul><ul><li>Vital Signs </li></ul></ul><ul><ul><li>Medical Consultation </li></ul></ul>
AHA <ul><li>FACTORS </li></ul><ul><li>Age </li></ul><ul><li>Sex </li></ul><ul><li>Heredity </li></ul><ul><li>FACTOIDS </li></ul><ul><li>Smoking </li></ul><ul><li>Cholesterol </li></ul><ul><li>Blood Pressure </li></ul><ul><li>Physical Inactivity </li></ul><ul><li>Obesity </li></ul><ul><li>Diabetes Mellitus </li></ul><ul><li>Stress </li></ul><ul><li>Socioeconomic Status </li></ul>
WOW! <ul><li>Oral Risk Management Protocol </li></ul><ul><ul><li>Caries and Periodontal Protocol </li></ul></ul><ul><li>AHA </li></ul><ul><ul><li>SBE Prophylaxis! </li></ul></ul><ul><li>Periodontal Pharmacotherapeutics </li></ul><ul><ul><li>What to use and when? </li></ul></ul>
WHAT WE KNOW <ul><li>If you have MØ+, you have potential </li></ul><ul><li>Plaque in the gums, plaque in the arteries </li></ul><ul><li>Bacterial endotoxins & Host cytokines </li></ul><ul><li>CHD yes, CVA maybe </li></ul><ul><li>ASA/NSAIA benefits </li></ul><ul><li>PD linked to many systemic diseases </li></ul>
DOCTOR DENTIST <ul><li>Paradigm shift </li></ul><ul><ul><li>Medical instead of mechanical </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>The tools are changing </li></ul></ul><ul><li>Rationales </li></ul><ul><ul><li>Now have systemic implications </li></ul></ul><ul><li>The Next Ten Years? </li></ul>
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