The Significance of Periodontal Infection in Cardiology


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The Significance of Periodontal Infection in Cardiology

  1. 1. Earn 3 CEUs This course was written for dentists, dental hygienists, and assistants.The Significance ofPeriodontal Infectionin CardiologyA Peer-Reviewed PublicationWritten by Stanley Shanies, MD, FACP and Casey Hein, BSDH, MBA PennWell is an ADA CERP recognized provider ADA CERP is a service of the American Dental Association to assist dental professionals in identifying quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit hours by boards of dentistry. PennWell is an ADA CERP Recognized Provider Concerns of complaints about a CE provider may be directed to the provider or to ADA CERP at Go Green, Go Online to take your courseReprinted from Grand Rounds, May 2006, Vol. 1, No. 2. This course has been made possible through an unrestricted educational grant. The cost of this CE course is $59.00 for 3 CEUs.Cancellation/Refund Policy: Any participant who is not 100% satisfied with this course can request a full refund by contacting the Academy of Dental Therapeutics and Stomatology in writing.
  2. 2. Educational Objectives eromas which result in myocardial infarction (MI) and stroke.1,2Upon completion of this course, the clinician will be able to do It is the atherosclerotic lesion that amplifies the risk for CVD.the following: Is human atherosclerosis an inevitability of aging? The1. Understand the risk factors associated with hypothesis that human atherosclerosis is not an absolute conse- cardiovascular disease quence of aging and can be reversed was put forth in the 1980s2. Understand the role of infection in the developing by Malinow’s pioneering work aimed at halting the progression atherosclerotic lesion and understand the evolution of of atherosclerosis and promoting its regression.3,4 Mounting these lesions evidence appears to strengthen Malinow’s hypothesis that old3. Understand the association of periodontal disease with age may not necessarily equate to atherosclerosis. A recent cardiovascular disease study of more than 1,000 participants with a mean age of 734. Understand the role of dental professionals in screening found that for older adults, periodontal disease, which is one of patients for cardiovascular disease the infections implicated as a cause of endothelial injury leading to atherosclerosis, is a modifiable risk indicator for elevated lev-Abstract els of systemic inflammatory markers, including interleukin-6Molecular and cellular biology and the physiologic mechanisms (IL-6), tumor necrosis factor (TNF- ), and hsCRP.5 Allof disease constitute the basis of treatment in both cardiology three of these markers are widely recognized as being associatedand periodontics. Recognizing inflammation as the common with periodontal infection.6–8 The question becomes, “Coulddenominator in the pathobiology of cardiovascular and peri- treatment of periodontal disease in patients both at an earlierodontal disease provides an excellent opportunity for dental stage and age translate into greater longevity?”and medical professionals to collaborate on decreasing patients’risk for cardiovascular disease (CVD), or its progression. This Challenges in Decreasing thearticle focuses on empowering dental and medical professionals Incidence and Severity of CVDto incorporate the latest evidence on the relationship of peri- More than 20 years have passed since Malinow tackled CVD.odontal and cardiovascular disease by presenting an in-depth With an array of therapeutic strategies at hand, many health-view of the inflammatory process involved with atherosclerosis. care providers hoped that CVD would be eliminated by the endFurther, this article will discuss the significance of infections of the 20th century. At the beginning of the 21st century, despitesuch as periodontal disease in increasing the systemic inflamma- cardiologists’ recommendations to patients for therapeutictory burden and risk for atherosclerosis and, thereby, increasing lifestyle changes targeting classic risk factors — a diet restrictedthe risk for CVD. In addition, a rationale for why periodontal in calories to reach a body mass index of <25 kg/m2; a waistdisease should be considered a risk correlate of CVD is pre- circumference <105 cm in men and <90 cm in women; physicalsented. Also discussed is the use of the Framingham CVD exercise, smoking cessation, and blood pressure control; andrisk assessment instrument and high-sensitivity C-reactive the widespread use of statins in treating hypercholesterolemiaprotein (hsCRP) testing in dental practices and screening for — CVD still accounts for 38% of all deaths in North America.2periodontal disease in medical practices. This article concludes Largely because of its rapidly increasing prevalence in Easternby challenging readers to realize the undeniable therapeutic Europe and developing countries, and the obesity trends andopportunity of medical-dental collaboration in reversing the rising incidence of diabetes in the West, coronary heart diseaserather somber trends in CVD. (CHD) is expected to be the main cause of death globally.9 Citation: Shanies, S. Hein, C. The significance of peri- However, about half of patients presenting with MI do not haveodontal infection in cardiology. Grand Rounds Oral-Sys Med. classic risk factors for CVD.10 CVD was once thought of as a2006;1:24– 33. disease primarily induced by accumulation of lipid-laden cells. (A complimentary copy of this article may be downloaded at What we now know is that high cholesterol is important in 50% of patients with coronary artery disease (CAD).1 “Even Key words: Periodontitis, cardiovascular disease, bacteria, with intensive statin therapy, the best current evidence-basedinflammation, risk factors treatment available, many patients will still have recurrent cardiovascular events.”11 Although statin therapies have beenIntroduction successful for a large segment of the population, it appears thatMost of us have heard the refrain from an old song, “The ankle the medical community may need to pursue approaches beyondbone is connected to the leg bone.” Can we now sing, “The statins to modify the course of vascular diseases.11gums are connected to the heart?” As unlikely as this may Hardly daunted by the most progressive disease-manage-sound, researchers and clinicians may have ample evidence ment strategies, the prediction, prevention, and treatment ofto support this claim. Pilot intervention studies are now un- CVD represents one of the greatest challenges facing all ofderway, but should we wait for those final answers before we us in the health-care arena. This dismal revelation begs anconsider periodontal disease as a risk correlate for CVD? And, important question: “If we are to implement the recommen-if we move ahead now, how do health-care providers implement dations made by the Surgeon General in the Oral Health inthe current evidence? America report,12 already five years old, and achieve the target Cardiologists and dental professionals appear to have a goals set by the Centers for Disease Control and Prevention,13common enemy — chronic inflammation and its potential to should we include in risk assessments for CVD those factorsaccelerate the process of atherosclerosis, a widely recognized associated but that, at present, are not proven to be causative,prelude to cardiovascular diseases. Science is beginning to re- independent, or quantitative?veal that destructive inflammatory periodontal diseases release The answer may be “yes,” but this level of comprehensivesubstances that are involved in arterial wall inflammation, care will require medical and dental professionals who aredevelopment of atherosclerosis, and rupture of established ath- willing to champion this message and initiate models of collab-2
  3. 3. Once coronary atherosclerosis is clinically manifested, the risk Table 1 Factors Associated With Increased Risk for CVD. 15 for future coronary events is much higher than that for patients (Correlated to the Framingham Heart Study.) without CVD, regardless of other risk factors.15 Therefore, the Framingham scores no longer apply.15 Should periodontal disease be added to this list? When considering the various risk factors for CHD (Table 1), it is important to understand that major risk factors are ad- Major Independent Risk Factors ditive in predictive power in that total risk can be estimated by • Advancing age the summation of the individual risks related to each factor.15 • Cigarette smoking However, the major risk factors for CVD as identified in Table • Diabetes 1 do not account for all the variations in the incidence and se- verity of CVD. Accordingly, it is important to point out that • Elevated blood pressure other, less well documented risk factors for CVD may play a • Elevated serum total (and LDL) cholesterol significant role.16 • Low serum HDL cholesterol A strong argument may be made that periodontal disease Predisposing Risk Factors should be considered both a predisposing and a conditional risk factor for CVD. Predisposing risk factors are agents that • Abdominal obesity§ worsen independent risk factors.15 The bidirectional relation- • Ethnic characteristics Periodontal ship between periodontal disease and diabetes would seem to • Family history of premature qualify periodontal disease as a predisposing risk factor for coronary heart disease disease? diabetic complications.17–21 Conditional risk factors are associ- • Obesity†§ ated with an increased risk for CVD, although their causative • Physical inactivity† contributions to CVD have not been well documented.15 Such • Psychosocial risk factors is the case for the correlation between periodontal disease and increased risk for atherosclerosis. The presence of predisposing Conditional risk factors and conditional risk factors in the assessment of risk for CVD • Elevated serum homocysteine may confer greater risk than revealed from the summation of • Elevated serum lipoprotein (a) the major risk factors.15 Although their contribution has not • Elevated serum triglycerides been quantified, this does not mean that they do not make an • Inflammatory markers (e.g. C-reactive protein) independent contribution to risk when they are present.15 Ac- • Prothrombotic factors (e.g. fibrinogen) cordingly, what may be left off this list of risk factors in Table • Small LDL particles 1 is the contribution of periodontal infection in accelerating atherosclerosis eventuating in CVD.† These risk factors are defined as major risk factors by the American Heart Association During the last 20 years there has been significant progress§ Body weights are currently defined according to BMI as follows: normal weight 18.5 in understanding the link between periodontal infections andkg/m 2 to 24.9 kg/m 2; overweight 25 kg/m 2 to 29 kg/m 2; obesity >30.0 kg/m 2; (obesityclass I 30.0 kg/m 2 to 34.9 kg/m 2; class II 35.9 kg/m 2 to 39.9 kg/m 2, class III ≥50 kg/m 2). risk for CVD such as heart disease22, stroke, and peripheral vas-Abdominal obesity is defined according to waist circumference: men >102 cm (>40") culature disease, all of which share atherosclerosis as a commonand women >88 cm (>35"). feature.16,23 Recent research found bacterial levels were elevated in only those patients with a history of myocardial infarction,orative care. The intervention trials necessary to prove a cause- suggesting that increased loads of subgingival bacteria presentand-effect relationship between periodontal disease and CVD a danger for systemic health.24are currently underway or about to be funded. Accumulation of The growing research to support the contribution of peri-that evidence will take years. In the meantime, do we not have odontal infection to the inflammatory burden is theorized toenough evidence to support periodontal disease at least as a risk be through both a direct action on blood vessel walls, and bycorrelate for CVD? indirectly inducing the liver to produce acute phase proteins The prevalence of both periodontitis and atherosclerosis is (e.g., CRP) (Figure 1).25 Until recently, DNA footprints com-rampant. Periodontal disease is a “preventable [and treatable] prised the bulk of evidence suggesting that periodontal bacteriacontributor to the burden of cardiovascular disease,”14 and as were directly involved in atherosclerosis. However, research atsuch, is a modifiable risk factor — a fact that may be escaping the University of Florida has demonstrated that Porphyromonasthe attention of both medical and dental professionals. If only gingivalis (P. gingivalis) and Actinobacillus actinomycetemcomi-a marginal association between these two diseases is found, tans (A. actinomycetemcomitans) are capable of adapting to theprevention and treatment of periodontal disease may have an vasculature to live in human atherosclerotic lesions.26 On the impact on the prevalence of CVD. It is not premature to include medical side, a study recently reported in the American Heartperiodontal disease as a risk correlate for CVD, and failure to do Journal found that periodontal disease is common in patientsso may forfeit an important therapeutic opportunity to reduce with MI and associated with elevated hsCRP levels typicalor eliminate a modifiable risk factor for CVD. of an enhanced systemic inflammatory response.27 These as- sociations were found to be independent of other contributingQuantifying Risk for CVD factors.27 Other studies indicate an association between peri-Table 1 classifies various risk factors according to their quanti- odontal disease and elevated hsCRP and IL-6, and, conversely,tative association with CVD as elucidated by the Framingham that periodontal treatment lowered hsCRP and IL-6 with a si-Heart Study, which estimates risk for people without clinical multaneous improvement in endothelial function.28 As compel-manifestations of CVD. Scores derived from the Framingham ling as this research may be, the truth is that the evidence onlyrisk assessment only apply to the primary prevention of CVD.15 supports, but does not prove, a causal association between 3
  4. 4. There are many studies to support the specific correlation Figure 1 ¥ of periodontal infection and atherosclerosis, and a few more Model for systemic spread of periodontal recent pieces of evidence merit mention. Various studies have infection and effects on the vasculature implicated P. gingivalis, a virulent periodontal pathogen, as part of a transient bacteremia that can lead to the direct inva- Periodontal sion of blood vessels.30 In addition, P. gingivalis is implicated Direct Indirect in several steps involved in the formation of the atherosclerotic Effect Infection Effect lesion.31,32 In 2003, it was reported that subjects with advanced Bacteria periodontal disease exhibited endothelial dysfunction and evi- or LPS dence of systemic inflammation (elevated serum CRP levels), Monocytes Monophages Liver placing them at increased risk for CVD.33 More recently, there is serological evidence that an infection caused by P. gingivalis increases the risk for MI; high P. gingivalis antibody levels have IL-1, IL-6 CRP, fibrinogen, been shown to predict MI independently of classical cardiovas- TNF lipid abnormalities, cular risk factors,34 and infection caused by major periodontal coagulation factors pathogens may be associated with future stroke.35 Periodontal Vascular disease was found to be a treatable, independent risk factor for Lesion cerebral ischemia in male subjects (<60 years of age). Those with severe periodontitis had a 4.3 times greater risk of cere-¥ Reprinted from Periodontics: Medicine, Surgery, and Implants, Rose LF, Mealey BL, Genco bral ischemia than subjects with mild periodontitis or healthyRJ, Cohen DW, pg 848, Copyright 2004, with permission from Elsevier. subjects.36 Gingivitis and severe radiological bone loss were also independently associated with the risk of cerebral ischemiaodontal disease and atherosclerosis-related diseases. Until this while tooth decay was not.36etiological mystery is decoded, we are faced with the dilemma A recent investigation demonstrated a direct relationshipof how to implement treatment strategies that are supported by between microorganisms from periodontal infection and sub-the existing body of evidence. clinical (undetected) atherosclerosis.37 This relationship was Although a combination of risk factors may contribute to the found to be independent of hsCRP.37 The same research foundprogression of an atherosclerotic lesion, researchers now consider that bacteria causally related to periodontitis are related to in-infection to be a significant inflammatory stimulus.28 Inflamma- creased carotid intima-media thickness (IMT),37 an importanttion is directly implicated in destabilization of atherosclerotic marker of early atherosclerosis. This was true even after adjust-plaque in the carotid artery1 and may lead to aneurism and embo- ing for conventional risk factors (i.e., age, race/ethnicity, bodylism.1 Seeding of live periodontal bacteria from the oral cavity to mass index (BMI), smoking, diabetes, systolic blood pressure,vessel walls,26 a hyperinflammatory response to those periodontal LDL, and high-density lipoprotein [HDL] cholesterol),37 pro-pathogens,29 and activation of proinflammatory mediators are viding even more evidence of a direct role of certain infections inthree biological mechanisms implicated in the induction of a the pathogenesis of atherosclerosis. The same study found thatsystemic inflammatory response.26 This chain of events may white blood cell values tend to rise with both increasing levels ofdescribe the link between periodontal disease and CVD. periodontopathic bacteria and increased carotid IMT.37 Similar To fully understand the significance of periodontal dis- research findings continue to accumulate, strengthening theease in the cascade of events implicated in the formation of evidence that inflammation, either direct or from a distance (asan atherosclerotic lesion, it is important that dental practi- in periodontal disease) is a primary etiology for affecting altera-tioners understand that infection is a well-established risk tions in endothelial function which, left untreated, eventuallyfactor for atheroma formation and thromboembolic events.16 develops into an atherosclerotic lesion.To that end, discussion and illustration of the role of infec- An atheroma forms in the arterial wall as a result of inflam-tion in the developing atherosclerotic lesion may help read- mation.1 The atheroma is made up of smooth muscle prolif-ers gain a more comprehensive understanding of this cascade eration in the media of the arterial wall.1 Other infl ammatory of pathological events. changes in the media are seen distorting the anatomy of the arterial wall.1 This is covered by a fibrous cap on the luminalThe Contribution of Infection in the surface narrowing the lumen to a greater or lesser extent,Developing Atherosclerotic Lesion depending on the circumstances.38 Some feel that distortionIt is known that atherosclerosis is the main cause of CVD.1,2 Pos- is more dangerous than luminal stenosis.38 Over time, the sible causes of the endothelial dysfunction that lead to athero- fibrous cap thins and ruptures with matrix metalloprotein-sclerosis include elevated and modified low density lipoprotein ases (MMPs) playing a role in the degradation of the collagen(LDL); free radicals caused by cigarette smoking; hypertension within the fibrous cap.38 This presents a rough surface toand diabetes; genetic alterations; and elevated plasma homo- flowing blood in the lumen.38 Platelets adhere to this surfacecysteine concentrations.1 Most germane are the studies that under the influence of adhesion factor activity, causing ahave also linked infection to atherosclerotic-induced diseases. coagulation cascade leading to an occluding clot, cutting offWhat has become apparent is that several types of microbial all blood flow.38 This results in stroke or MI, depending onpathogens may contribute to atherosclerosis, making it highly the location.38unlikely that a single microbe causes atherosclerosis.2 It is now Ross wrote a 1999 review article in the New England Jour-thought that the cumulative burden of infection at various sites nal of Medicine titled “Atherosclerosis — An Inflammatoryis what affects the progression of atherosclerosis and its clinical Disease,” which is used in teaching institutions to provide amanifestations of CVD.2 step-by-step description of the development of the atheroscle-4
  5. 5. Figures 2 –5: Evolution of the atherosclerotic lesionFigure 2 — Endothelial dysfunction in atheroslerosis. 1 Figure 3 — Fatty-streak formation in atherosclerosis. 1The earliest changes preceding the formation of atherosclerotic lesions Fatty streaks initially consist of lipid-laden monocytes and macrophagesinvolve the endothelial lining of the vessel lumen. The changes include (foam cells) together with T-lymphocytes. Later, they are joined by in-increased endothelial permeability that leads to acculumation of lipo- creasing numbers of smooth muscle cells, some of which may also containproteins and development of the fatty streak; up-regulation of endo- varying amounts of lipid. The increasing population of smooth musclethelial adhesion molecules that facilitate the aggregation of monocytes, cells is promoted by various growth factors, such as Platelet-DerivedT-lymphocytes, and blood platelets; and endothelial/platelet interactions Growth Factor (PDGF), Fibroblast Growth Factor (FGF), and Transformingresulting in the release of growth factors that, in turn, promote progres- Growth Factor-ß (TGF-ß).sive development of the lesion.Figure 4 — Formation of an advanced, complicated lesion Figure 5 — Unstable fibrous plaques in atherosclerosis. 1of atherosclerosis. 1 Rupture or ulceration of the fibrous cap can lead to hemorrhage andIntermediate and advanced atherosclerotic lesions are characterized by a thrombosis and usually occurs at sites where the connective tissue layer isfatty streak covered by a fibrous connective tissue cap. The cap represents thin. Thinning of the fibrous cap is apparently because of the continuinga healing response to injury and forms a barrier between the underlying influx and activation of macrophages, which release metalloproteinaseslesion and the vessel lumen. The fibrous connective tissue layer is infil- and other proteolytic enzymes. The enzymes degrade collagen and non-trated by lipid-filled macrophages and smooth muscle cells, all of which collagenous matrix proteins, which then leads to hemorrhage, thrombuscover a mixture of leukocytes, extracellular lipids, and debris that, in turn, formation, and occlusion of the vessel. In some cases, an embolus ofmay form a necrotic core. clotted blood may be released and occlude a downstream vessel. Medical illustrations used with permission from the New England Journal of Medicine
  6. 6. rotic lesion.1 In this review, Ross detailed the atherosclerotic dental practices has the potential to become a significant toolprocess beginning with endothelial dysfunction, the formation for identification of patients at risk for CVD. This may beof the fatty streak, and then the formation of the advanced especially valuable in primary prevention of CVD. Currentcomplicated atherosclerotic lesion, ending with how unstable research considers subclinical (undetected) inflammation to befibrous plaque can rapidly lead to thrombosis. Illustrations and an accelerant of vascular inflammation and markers of inflam-accompanying explanations of the contribution of infection in mation (both systemic and local), which, in turn, appear to playthe atherosclerotic process are provided in Figures 2 to 5 to help a central role in the development and progression of atheroscle-readers better understand the pathobiological cascade of events rosis.10 Indeed, many patients seen by health-care professionalsimplicated in the formation of an atherosclerotic lesion. are at increased risk for MI or stroke because of undiagnosed and asymptomatic atherosclerosis which may be accelerated byMaking the Case for hsCRP Testing chronic periodontal Dental Practices In 2002, the Centers for Disease Control and PreventionIt is becoming increasingly clear that the variety of cardiovas- and the American Heart Association held a conference tocular events cannot be explained by a single pathobiological examine (among other things) the selection and use of inflam-pathway. The relationship between novel biological markers matory markers to predict CVD risk. Recommendations madeof inflammation and traditional risk factors, such as high blood at the conference which have specific relevance to the presentpressure, smoking, obesity, diabetes, low levels of physical discussion follow:42activity, and use of hormone-replacement therapy, may be ofvariable importance for individual patients.39 This has spawned 1) Of all the inflammatory markers identified, hsCRP, as ana search for other factors that may be implicated and, when independent marker of risk, may be used at the discretion ofpresent, help to identify patients at greater risk for MI and other the physician as part of an office-based global risk assessmentcardiovascular events.10 Certain markers of inflammation (sys- (i.e., the Framingham Heart Study) in adults withouttemic and local) appear to play a central role in the development known CVD. HsCRP may identify those patients for furtherand progression of atherosclerosis.10 HsCRP, one of the acute- intervention or therapy in the primary prevention of CVD.42phase proteins produced by the liver in response to infection, isa specific systemic marker of vascular inflammation that appears Dental professionals also are well-positioned to assist pa-to have a strong association with adverse vascular events.39 tients in assessing their global risk for CVD through use of an Both hsCRP and LDL cholesterol levels are elevated in assessment such as the Framingham instrument.people at risk for cardiovascular events. However, hsCRPand LDL cholesterol measurements tend to identify different 2) Testing for hsCRP provides an additive element to global riskhigh-risk groups.39 Researchers have found that independent assessment. As a result, patients without known CVD whoeffects were observed for hsCRP in analyses adjusted for all were not previously considered to be at risk will be identifiedcomponents of the Framingham risk score39 (i.e., traditional and targets for more aggressive risk reduction interventions.risk factors for CVD). Specifically, hsCRP and LDL choles- It was recommended that hsCRP be measured in patients whoterol levels are minimally correlated and hsCRP has been found are at intermediate risk of CHD per 10 years (as indicatedto be a stronger predictor of future cardiovascular events than in global risk assessment) to direct further evaluation andLDL cholesterol.39 This advantage persisted after adjusting for therapy in the primary prevention of CVD.42all traditional cardiovascular risk factors and included the effectof hormone-replacement therapy at baseline.39 The researchers A good example of this would be a patient who has beenfurther concluded that the combined evaluation of both hsCRP identified by a dental professional as being at intermediate riskand LDL cholesterol proved to be a superior method of detect- of CVD via global risk assessment such as the Framingham risking risk for cardiovascular events than measurement of either assessment. For example, if a person’s cardiovascular risk scorebiological marker alone.39 — judged by global risk assessment — is low (the possibility What is the normal range of hsCRP level? 40 of developing CVD is <10% in 10 years), hsCRP testing is not• If hsCRP level is lower than 1.0 mg/L, a person has a low immediately warranted.39 If the risk score is in the intermediate risk of developing cardiovascular disease. range (10% to 20% in 10 years), such a test can help predict a• If hsCRP is between 1.0 mg/L and 3.0 mg/L, a person has cardiovascular and stroke event and help direct further evalua- an average risk. tion and therapy.39 However, the benefits of such therapy based• If hsCRP is higher than 3.0 mg/L, a person is at high risk. on this strategy remain uncertain.39 If a dental professional intercepts a person with a high risk score (>20% in 10 years) Low-grade chronic inflammation as measured by hsCRP or established heart disease or stroke, this is an individual whopredicts future risk of acute coronary syndromes independent should receive intensive medical care regardless of hsCRP lev-of traditional cardiovascular risk factors.41 Because periodontal els38 and should be triaged to the care of a cardiologist as sooninfection appears to be a source of low-grade chronic infec- as possible.tion, the use of hsCRP testing in dental practices provides anexcellent opportunity for identifying patients at risk for acute 3) It was recommended that patients with persistentlycoronary syndromes. unexplained marked elevation of hsCRP (>10 mg/L) after repeated testing should be evaluated for noncardiovascularThe Role of Dental Professionals in causes, such as infection and inflammation.42Screening Patients for CVD Risk —Along with monitoring blood pressure, which has long been These are the types of patients cardiologists should refer toroutine in practice, the addition of chairside hsCRP testing in periodontists to be examined for periodontal disease.6
  7. 7. 4) It was suggested that detection of an elevated hsCRP plaque), which ultimately leads to rupture, in-situ thrombo- might serve to motivate patients to adhere to better sis, and subsequent vascular events.46 Although larger studies preventive therapies.42 are needed to investigate its potential to reduce the risk of rupture of atherosclerotic plaque, it appears that subantimi- This might be the case for a prediabetic patient whose crobial doses of doxycycline, approved by the U.S. Food andhsCRP is tested by a dental hygienist chairside and discovered Drug Administration for suppression of collagen-destroyingto be edging toward “high normal” (2 mg/L to 10 mg/L), which enzymes in the treatment of periodontal disease, may alsois predictive of heart disease. In this situation, a dental hygienist have cardioprotective benefits.46has a valuable role to play in motivating that patient to adhere toproper diet, physical fitness programs, compliance to medica- Conclusiontion regimens, or, possibly, smoking cessation counseling. Despite the fact that the formation of the atherosclerotic le- sion and its impending threat to cardiovascular health has aTesting for hsCRP in Dental Practices very complex etiology, dental screening to identify patientsIs it time for dental professionals to screen patients for risk of at risk for CVD and those patients with diagnosed CVD whofuture cardiovascular events by performing chairside testing are at greater risk for recurrent cardiovascular events offersfor hsCRP? Yes, and those technologies are now entering the an undeniable intervention opportunity. Likewise, physi-health-care market. cians have an enormous part to play by screening patients The cardiologist who co-authored this article frequently for periodontal disease.asks new patients who have heart disease or who are at high For patients at intermediate risk (10% to 20% risk ofrisk for heart disease when they last saw their dentists, and CHD per 10 years) as defined by the Framingham risk score,whether they were examined for periodontal disease. He also testing for hsCRP may help direct further evaluation andvisually examines the gingival tissue and general conditions of therapy in primary prevention for CVD.47 For patients withthe teeth. An example of collaborative care involves a young, stable coronary disease and acute coronary syndromes, in-non-obese female patient with an elevated hsCRP, but normal office testing in dental practices for hsCRP may prove to beserum lipids and blood pressure, who presented with severe invaluable in identifying those patients who require signifi-gingival inflammation. The cardiologist referred this patient cantly more aggressive therapies provided by a periodontist. Four months later, following periodontal Although the cardioprotective benefits of periodontaltherapy, her hsCRP was normal. treatment remain speculative at present, awareness of the re- The cardioprotective benefits of periodontal treatment lationship between the increased burden of infectious agentsmay represent an efficacious modification to contemporary and systemic inflammation may have a significant effecttherapies for vascular diseases. Several pilot studies have on the prevention and treatment of chronic inflammatoryshown that periodontal therapy consisting of scaling and root diseases and conditions. Transition toward interdisciplinaryplaning and application of antimicrobial agents were effective health-care management must increase to better target thosein reducing levels of serum inflammatory markers, specifically at high risk and to devise a multidisciplinary integratedhsCRP, IL-6, and TNF- .43,44 However, larger scale, random- care pathway for CVD. Those physicians and dentists whoized interventional clinical trials are needed to investigate the collaborate on this integrated care pathway will be ahead ofpotential cardiovascular benefits of periodontal therapy.7 If the curve.future research provides evidence that treatment of periodon- It is not unusual to hear from physicians that they havetitis reduces hsCRP and/or decreases the incidence of CVD, seen patients with hyperparathyroidism, diabetes, osteopo-this would provide a strong rationale for a change in health- rosis, and various other diseases that were first diagnosed incare policy that would position periodontal care as medically the dental office. Indeed, astute dentists and dental hygien-necessary for the prevention and management of CVD.7 In ists are often the first to note an undesirable side effect ofthe meantime, it is time for physicians and other nondental calcium channel blockers (i.e. drug-induced gingival over-health-care providers to begin to identify those patients who growth). Many within the medical profession also recognizeare at greater risk for periodontal disease because of their indi- the significant contributions of many dental professionals invidual risk profiles. Specifically, patients who smoke are at 3 to monitoring patients’ blood pressure. It is important to real-7 times greater risk and patients with diabetes are at 2 to 5 times ize that we are now in an unprecedented era of explosion ofgreater risk for developing periodontal disease.45 Patients who research related to periodontal medicine. For the well-beingreport that a sibling or parent lost their teeth at an early age of our patients, the time has come for physicians, dentists,may be genetically predisposed to periodontal disease with an nurses, and dental hygienists to work together to identifyodds ratio that confers 3 to 5 times greater risk for developing those at risk, both for atherosclerosis and periodontal dis-periodontal disease.45 Those patients who both smoke and ease. Indeed, we are all treating “a patient,” not just one partwho are genotype positive have an 8 to 10 times greater risk or one organ.for periodontal disease.45 These scenarios represent excellent It is interesting that the oldest medical school in theopportunities for the medical community to screen for peri- world, the University of Bologna in Bologna, Italy (foundedodontal disease and triage patients to dental professionals for in 1088), still requires all medical students to take a one-yearevaluation and treatment of periodontal disease. course in oral medicine and dentistry. Nine hundred seven- Discussion of the significance of periodontal infection teen years later, all physicians and dentists must realize thatin cardiology would be incomplete without mentioning the we treat an organism. The mouth is attached to the body andpotential role subantimicrobial doses of doxycycline may each may have an effect on the health of the other. We mustplay in inhibiting MMPs. MMPs participate in degradation remember the ankle bone is connected to the leg bone and,of the fibrous cap of an atherosclerotic lesion (the vulnerable indeed, the oral cavity is connected to the 7
  8. 8. References levels. Am Heart J. 2004;147(6):1005–1009.1. Ross R. Atherosclerosis — an inflammatory disease. N Engl J Med. 1999;340(2): 28. Offenbacher S, Beck J. A perspective on the potential cardioprotective benefits of 115–126. periodontal therapy. Am Heart J. 2005;149(6):950–954.2. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 29. Genco RJ, Offenbacher S, Beck J, et al. Cardiovascular disease and oral infections. In: 2005;352(16):1685–1695. Rose LF, Mealey BL, Genco RJ, et al (eds). Periodontal Medicine. Hamilton, Ontario,3. Malinow MR. Atherosclerosis. Regression in nonhuman primates. Circ Res. Canada: BC Decker, Inc; 2000:71–74. 1980;46(3):311–320. 30. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):4. Malinow MR. Atherosclerosis. Progression, regression, and resolution. Am Heart J. 1135–1143. 1984;108(6):1523–1537. 31. Kuramitsu HK, Kang IC, Qi M. Interactions of Porphyromonas gingivalis with host cells:5. Bretz WA, Weyant RJ, Corby PM, et al. Systemic inflammatory markers, periodontal implications for cardiovascular diseases. J Periodontol. 2003;74(1):85–89. diseases, and periodontal infections in an elderly population. J Am Geriatr Soc. 2005 32. Miyakawa H, Honma K, Qi M, et al. Interaction of Porphyromonas gingivalis with Sep;53(9):1532–1537. low-density lipoproteins: implications for a role for periodontitis in atherosclerosis. J6. The Research, Science, and Therapy Committee of the American Academy Periodontol Res. 2004;39(1);1–9. of Periodontology. The pathogenesis of periodontal diseases. J Periodontol. 33. Amar S, Gokce N, Morgan S, et al. Periodontal disease is associated with brachial artery 1999;70(4);457–470. endothelial dysfunction and systemic inflammation. Arterioscler Thromb Vasc Biol.7. American Academy of Periodontology coordination meeting on oral health 2003;23(7):1245–1249. and systemic health. Periodontal medicine: health policy implications. Geneva, 34. Pussinen PJ, Alfthan G, Tuomilehto J, et al. High serum antibody levels to Switzerland, December 5 and 6, 2002. J Periodontol. 2003;74(7):1080–1095. Porphyromonas gingivalis predict myocardial infarction. Eur J Cardiovasc Prev Rehabil.8. Noack B, Genco RL, Trevisan M, et al. Periodontal infections contribute to elevated 2004;11(5):408–411. systemic C-reactive protein level. J Periodontol. 2001;72(9):1221–1227. 35. Pussinen PJ, Alfthan G, Rissanen H, et al. Antibodies to periodontal pathogens and9. World Health Organization. The Atlas of Heart Disease and Stroke. 2005. Available stroke risk. Stroke. 2004:35(9):2020. at: Accessed 36. Grau AJ, Becher H, Ziegler CM, et al. Periodontal disease as a risk factor for ischemic Dec 11, 2005. stroke. Stroke. 2004;35(2):496–501.10. Koenig W. C-reactive protein: risk assessment in the primary prevention of 37. Desvarieux M, Demmer RT, Rundek T. Periodontal microbiota and carotid intima-media atherosclerotic disease. Has the time come for including it in the risk profile? Ital Heart thickness; the oral infections and vascular disease epidemiology study (INVEST). J. 2001;2(3):157–163. Circulation. 2005;111(5):576–582.11. Cannon CP. The ideal cholesterol. JAMA. 2005;294(19):2492–2494. 38. Fuster V, Moreno PR, Fayad ZA, et al. Atherothrombosis and high risk plaque. Part I:12. Satcher D. US Department of Health and Human Services. Oral Health in America: A Evolving Concepts. J Am Coll Cardiol. 2005;46(6):937–954. Report of the Surgeon General. May 2000. Available at: http://www.surgeongeneral. 39. Ridker PM, Rifai N, Rose L, et al. Comparison of C-reactive protein and low-density gov/library/oralhealth. Accessed Nov 18, 2005. lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J13. US Department of Health and Human Services, Public Health Service. Healthy People Med. 2002;347(20):1557–1565. 2010 Progress Review-Heart Disease and Stroke. Available at: www.healthypeople. 40. American Heart Association. Inflammation, Heart Disease and Stroke: The Role of C- gov/data/2010prog/focus12. Accessed April 15, 2005. Reactive Protein. Nov 2005. Available at: Beck JD, Elter JR, Heiss G, et al. Relationship of periodontal disease to carotid jhtml?identifier=4648. Accessed Nov 18, 2005. artery intima-media wall thickness: The atherosclerosis risk in communities study. 41. Shishehbor MH, Bhatt DL. Inflammation and atherosclerosis. Curr Atheroscler Rep. Atheroscler, Thromb, and Vasc Biology. 2001;21(11):1816–1822. 2004;6(2):131–139.15. Grundy SM, Pasternak R, Greenland P, et al. AHA/ACC scientific statement: Assessment 42. Smith SC Jr, Anderson JL, Cannon RO, et al. CDC/AHA Workshop on Markers of of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement Inflammation and Cardiovascular Disease: Application to Clinical and Public Health for health-care professionals from the American Heart Association and the American Practice: report from the clinical practice discussion group. Circulation. 2004;110(25): College of Cardiology. J Am Coll Cardiol. 1999;34(4):1348–1359. E550–E553.16. Jin LJ, Chiu GK, Corbet EF. Are periodontal diseases risk factors for certain systemic 43. D’Aiuto FD, Parkar M, Andreou G. Periodontitis and systemic inflammation: Control of disorders—what matters to medical practitioners? Hong Kong Med J. 2003;9(1): the local infection is associated with a reduction in serum inflammatory markers. J 31–37. Dent Res. 2004;83(2):156–160.17. Grossi SG, Genco RJ. Periodontal disease and diabetes mellitus: a two-way relationship. 44. Iwamoto Y, Nishimura F, Soga Y, et al. Antimicrobial periodontal treatment decreases Ann Periodontol. 1998;3(1):51–61. serum C-reactive protein, tumor necrosis factor-α, but not adiponectin a levels in18. Nishimura F, Takahashi K, Kurihara M, et al. Periodontal disease as a complication of patients with chronic periodontitis. J Periodontol. 2003;74(8):1231–1236. diabetes mellitus. Ann Periodontol. 1998;3(1):20–29. 45. Cobb CM, Callan DP. Flashpoint in periodontics: patient referral. Triage. 2005;1(2):19. Schmidt AM, Weidman E, Lalla E, et al. Advanced glycation endproducts (AGEs) 12–16. induce oxidant stress in the gingiva: a potential mechanism underlying accelerated 46. Brown DL, Desai KK, Vakili BA, et al. Clinical and biochemical results of the periodontal disease associated with diabetes. J Periodontol Res. 1996;31(7): metalloproteinase inhibition with subantimicrobial doses of doxycycline to prevent 508–515. acute coronary syndromes (MIDAS) pilot trial. Arterioscler Thromb Vasc Biol.20. Ryan ME, Ramamurthy NS, Golub LM. Tetracyclines inhibit protein glycation in 2004;24(4):733–738. experimental diabetes. Adv Dent Res. 1998;12(2):152–158. 47. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and21. Brownlee M. Glycation products and the pathogenesis of diabetic complications. cardiovascular disease: application to clinical and public health practice: a statement Diabetes Care. 1992;15(12):1835–1843. for health-care professionals from the Centers for Disease Control and Prevention and22. Dorfer CE, Becher H, Ziegler CM, et al. The association of gingivitis and periodontitis the American Heart Association. Circulation. 2003;107(3):499–511. with ischemic stroke. J Clin Periodontol. 2004;31(5):396–401.23. Fiehn NE, Larsen T, Christiansen N, et al. Identification of periodontal pathogens in Disclaimer atherosclerotic vessels. J Periodontol. 2005;76(5):731–736. The authors of this course have no commercial ties with the24. Dögan B, Buduneli E, Emingil G, et al. Characteristics of periodontal microflora in acute sponsors or the providers of the unrestricted educational grant myocardial infarction. J Periodontol. 2005;76(5):740–748. for this course.25. Rose LF, Mealey BL, Genco RJ, et al (eds). Periodontics: Medicine, Surgery, and Implants. St Louis, Mo: CV Mosby; 2004:848.26. Kozarov EV, Dom BR, Shelburne CE, et al. Human atherosclerotic plaque contains Reader Feedback viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. We encourage your comments on this or any PennWell course. Arterioscler Thromb Vasc Biol. 2005;25(3):E17–E18. For your convenience, an online feedback form is available at27. Deliargyris EN, Madianos PN, Kadoma W, et al. Periodontal disease in patients with acute myocardial infarction: prevalence and contribution to elevated C-reactive protein8
  9. 9. Questions1. About half of patients presenting 8. All the following statements are 14. If a person’s cardiovascular risk with myocardial infarction, MI, true EXCEPT: score — judged by global risk do not have “classic” risk factors a. If hsCRP level is lower than 2.0 mg/L, a person assessment — is in the intermediate has a low risk of developing cardiovascular for cardiovascular disease, CVD. disease within the next 10 years. range (10% to 20% in 10 years), what One risk factor for MI that is not b. If hsCRP is between 1.0 and 3.0 mg/L, a person test/measurement can help predict has an average risk of developing cardiovascular a cardiovascular and/or stroke event currently considered a “classic” or disease within the next 10 years. major risk factor for CVD is: c. If hsCRP is higher than 3.0 mg/L, a person is and help direct further evaluation a. Diabetes at high risk of developing cardiovascular disease and therapy? b. Periodontal disease within the next 10 years. a. HbA1c d. If hsCRP level is lower than 1.0 mg/L, a person b. HDL c. Low serum HDL cholesterol has a low risk of developing cardiovascular d. Elevated LDL cholesterol c. hsCRP disease within the next 10 years. d. Blood pressure2. CVD accounts for ___________ of 9. All the following are implicated in 15. ______________ play a role in the all deaths in North America. the theorized relationship between periodontal disease and a systemic degradation of collagen within the a. 20% b. 33% response EXCEPT: fibrous cap on the luminal surface c. 38% a. A genetically programmed viral response that leads to rupture and thrombosis d. 47% b. Activation of proinflammatory mediators of an atherosclerotic lesion. c. A hyperinflammatory response to a. MMPs3. The intervention trials necessary to periodontal pathogens d. Seeding of live periodontal bacteria from the oral b. Blood platelets prove a cause-and-effect relation- cavity to vessel walls c. Fibroblast growth factor ship between periodontal disease d. None of the above 10. Which of the following combina- and CVD: 16. It has been recommended that tions of bacteria did University of a. Were completed in 1999 hsCRP be measured in patients Florida researchers recently demon- b. Will be completed at the end of 2006 strate are capable of adapting to the at intermediate risk of CHD per c. Have not been contemplated at this time vasculature and living within human ________ years. d. Are currently underway or about to be funded atherosclerotic lesions? a. Two4. The earliest change preceding a. Streptococcus intermedius and Actinobacillus b. Five actinomycetemcomitans c. Ten the formation of atherosclerotic b. Porphyromonas gingivalis and Actinobacillus d. Twenty lesions is: actinomycetemcomitans a. Activation by macrophages c. Tannerella forsythia and Campylobacter rectus 17. Patients with diabetes are at d. Prevotella intermedia and Treponema denticola b. Increased endothelial permeability ___________ greater risk for c. Infiltration by lipid-filled macrophages 11. One study found that individuals developing periodontal disease than d. Increasing numbers of smooth muscle cells with severe periodontitis had a ____ non-diabetics. times greater risk of ischemic stroke a. 1 to 35. The marker of vascular inflamma- than subjects with mild periodontitis b. 3 to 7 tion that appears to be most closely or healthy subjects. c. 2 to 5 associated with greater risk for a. 1.3 d. 2 to 7 myocardial infarction is: b. 2.3 a. TNF- c. 4.3 18. Subantimicrobial doses of d. 4.5 ____________ may have cardio- b. hsCRP c. Cholesterol levels 12. White blood cell values tend to protective benefits. d. Matrix metalloproteinases rise with: a. Penicillin a. Increasing levels of periodontopathic bacteria b. Doxycycline6. Biological mechanisms implicated in and increased carotid IMT c. Chlorhexidine gluconate the induction of a systemic inflam- b. Increasing levels of periodontopathic bacteria d. Metronidazole matory response include: and decreased carotid IMT c. Decreasing levels of periodontopathic bacteria 19. The Framingham risk assessment a. Activation of pro-inflammatory mediators and increased carotid IMT scores apply to: b. Seeding of live periodontal bacteria from the oral d. None of the above cavity to vessel walls a. Primary prevention of CVD c. Seeding of live cariogenic bacteria to vessel walls 13. All the following are thought b. Secondary prevention of CVD to play roles in endothelial c. Primary and secondary prevention of CVD d. a and b dysfunction that leads to d. None of the above7. Periodontal infection is a atherosclerosis EXCEPT: 20. Elevated serum triglycerides are a: well-established risk factor for a. Osteoporosis b. Genetic alterations a. Predisposing risk factor thromboembolic events. b. Conditional risk factor c. Elevated plasma homocysteine concentrations a. True d. Elevated and modified low density lipoprotein, c. Major risk factor b. False LDL, cholesterol d. Dominant risk 9
  10. 10. ANSWER SHEET The Significance of Periodontal Infection in Cardiology Name: Title: Specialty: Address: E-mail: City: State: ZIP: Telephone: Home ( ) Office ( ) Requirements for successful completion of the course and to obtain dental continuing education credits: 1) Read the entire course. 2) Complete all information above. 3) Complete answer sheets in either pen or pencil. 4) Mark only one answer for each question. 5) A score of 70% on this test will earn you 3 CE credits. 6) Complete the Course Evaluation below. 7) Make check payable to PennWell Corp. Mail completed answer sheet to Educational Objectives Academy of Dental Therapeutics and Stomatology, 1. Understand the risk factors associated with cardiovascular disease A Division of PennWell Corp. P.O. Box 116, Chesterland, OH 44026 2. Understand the role of infection in the developing atherosclerotic lesion and understand the evolution of these lesions or fax to: (440) 845-3447 3. Understand the association of periodontal disease with cardiovascular disease 4. Understand the role of dental professionals in screening patients for cardiovascular disease For immEdiatE results, go to Course Evaluation and click on the button “take tests Online.” answer sheets can be faxed with credit card payment to Please evaluate this course by responding to the following statements, using a scale of Excellent = 5 to Poor = 0. (440) 845-3447, (216) 398-7922, or (216) 255-6619. 1. Were the individual course objectives met? Objective #1: Yes No Objective #3: Yes No P ayment of $49.00 is enclosed. (Checks and credit cards are accepted.) Objective #2: Yes No Objective #4: Yes No If paying by credit card, please complete the 2. To what extent were the course objectives accomplished overall? 5 4 3 2 1 0 following: MC Visa AmEx Discover Acct. Number: _______________________________ 3. Please rate your personal mastery of the course objectives. 5 4 3 2 1 0 Exp. Date: _____________________ 4. How would you rate the objectives and educational methods? 5 4 3 2 1 0 Charges on your statement will show up as PennWell 5. How do you rate the author’s grasp of the topic? 5 4 3 2 1 0 6. Please rate the instructor’s effectiveness. 5 4 3 2 1 0 7. Was the overall administration of the course effective? 5 4 3 2 1 0 8. Do you feel that the references were adequate? Yes No 9. Would you participate in a similar program on a different topic? Yes No 10. If any of the continuing education questions were unclear or ambiguous, please list them. ___________________________________________________________________ 11. Was there any subject matter you found confusing? Please describe. ___________________________________________________________________ ___________________________________________________________________ 12. What additional continuing dental education topics would you like to see? ___________________________________________________________________ ___________________________________________________________________ AGD Code 490 PLEASE PHOTOCOPY ANSWER SHEET FOR ADDITIONAL PARTICIPANTS. AUTHOR DISCLAIMER INSTRUCTIONS COURSE CREDITS/COST RECORD KEEPINGThe authors of this course have no commercial ties with the sponsors or the providers of All questions should have only one answer. Grading of this examination is done All participants scoring at least 70% (answering 14 or more questions correctly) on the PennWell maintains records of your successful completion of any exam. Please contact ourthe unrestricted educational grant for this course. manually. Participants will receive confirmation of passing by receipt of a verification examination will receive a verification form verifying 3 CE credits. The formal continuing offices for a copy of your continuing education credits report. This report, which will list form. Verification forms will be mailed within two weeks after taking an examination. education program of this sponsor is accepted by the AGD for Fellowship/Mastership all credits earned to date, will be generated and mailed to you within five business days SPONSOR/PROVIDER credit. Please contact PennWell for current term of acceptance. Participants are urged to of receipt.This course was made possible through an unrestricted educational grant. No EDUCATIONAL DISCLAIMER contact their state dental boards for continuing education requirements. PennWell is amanufacturer or third party has had any input into the development of course content. The opinions of efficacy or perceived value of any products or companies mentioned California Provider. The California Provider number is 3274. The cost for courses ranges CANCELLATION/REFUND POLICYAll content has been derived from references listed, and or the opinions of clinicians. in this course and expressed herein are those of the author(s) of the course and do not from $49.00 to $110.00. Any participant who is not 100% satisfied with this course can request a full refund byPlease direct all questions pertaining to PennWell or the administration of this course to necessarily reflect those of PennWell. contacting PennWell in writing.Machele Galloway, 1421 S. Sheridan Rd., Tulsa, OK 74112 or Many PennWell self-study courses have been approved by the Dental Assisting National Completing a single continuing education course does not provide enough information Board, Inc. (DANB) and can be used by dental assistants who are DANB Certified to meet © 2008 by the Academy of Dental Therapeutics and Stomatology, a division COURSE EVALUATION and PARTICIPANT FEEDBACK to give the participant the feeling that s/he is an expert in the field related to the course DANB’s annual continuing education requirements. To find out if this course or any other of PennWellWe encourage participant feedback pertaining to all courses. Please be sure to complete the topic. It is a combination of many educational courses and clinical experience that PennWell course has been approved by DANB, please contact DANB’s Recertificationsurvey included with the course. Please e-mail all questions to: allows the participant to develop skills and expertise. Department at 1-800-FOR-DANB, ext. 445. 10