Periodontal disease (parodontosis) as risk factor for cardiovascular diseases (heart attack, stroke)
Cardiovascular diseases include chronic pathologies having a multifactorial etiology that affect heart and blood vessels and are the first cause of death in the U.S.A, Europe and Asia. The most important of them affect the coronary arteries (coronary disease) which bring oxygenated blood to the heart. Because of their small diameter, in case of sustained obstruction of the blood flow (atherosclerosis) they are no more able to bring oxygen and nutrients to the myocardium. The narrowing of the vascular lumen due to atherosclerosis is determined by the buildup of cholesterol, cholesterol esters, calcium ions, fibroblasts and immune system cells deposits on the vessel walls. The resulting plaques can break down and produce clots which can migrate and occlude distally arteries having a narrower diameter: this will result in a necrosis of the affected area (heart attack or brain stroke).
Studying the known risk factors (hypertension, diabetes mellitus, age, high cholesterol and triglyceride plasmatic levels, smoke, stress, alcohol consumption, etc.) it is possible to ascribe them only the 2/3 of the new cases of cardiovascular diseases: for this reason the researchers have started to investigate new possible risk factors. From the studies conducted in the last decades it comes out that inflammation plays an important role in the pathogenesis of atherosclerosis and that the setting up of a chronic and systemic inflammatory reaction increases the risk of cardiovascular accidents.
Considering the existence of numerous common elements (age, diabetes mellitus, stress, smoke) as risk factors of cardiovascular diseases and periodontal disease, the multifactorial etiology chronic inflammation of the support tissues of the tooth, in the last decade the attention of the world medical and dental community has started to study possible correlations between the two pathologies.
CORRELATION CARDIOVASCULAR DISEASES-PERIODONTAL DISEASE
An accurate revision of the literature suggests the existence of a link between the periodontal disease and cardiovascular problems which may show itself in two different ways. The direct mechanism consists in the hypothesis that periodontal pathogenic bacteria move from the oral tissues to the bloodstream (bacteremia) and from here to distant locations during causal therapy or during simple periodontal probing.
To support this hypothesis there is the ability showed by the P. gingivalis to invade, in cell cultures, the endothelial wall and the discovery of periodontal pathogens in atheromasic plaques in specimens obtained from carotid endarterectomy.
The indirect mechanism makes reference to local production of inflammatory mediators able to reach the bloodstream and cause vascular damages in distant areas. The release of interleukins and tumor necrosis factor-a by the monocytes and the endothelial cells would then trigger the hepatic release of acute phase proteins, reactive C protein and fibrinogen, haptoglobin, a-1, antitrypsin which have the ability of promoting the deposit of low density lipoproteins and cholesterol along the arteries vascular walls, platelets aggregation and the activation of the clotting cascade, thus increasing the genetic risk of blood clot.
This hypothesis becomes even stronger if scientific evidence which relates other inflammatory pathologies, such as SLE (Systemic Lupus Erythematosus) and reumathoid arthritis, with a growing cardiovascular risk is taken into account.
This indirect effect of periodontal disease is supported by the correlation found in different clinical and epidemiological studies between that disease and high plasmatic levels of reactive C protein and other inflammatory biomarkers. Cohort and case-control studies have further showed a correlation between endothelial dysfunction (endothelial dysfunction may influence the slow atherogenic process and, in the presence of acute inflammation may give rise to an acute cardiovascular event), atherosclerosis and growing risk of heart disease and heart attack.
M. TONETTI’S STUDY
Starting from the presupposition that a systemic inflammatory reaction can cause vascular damage, the work Maurizio Tonetti and his research group published in 2007 aimed at researching the possible link that would involve periodontal disease on the basis of the observation of the effects of mechanical causal therapy on the endothelial function assessed 6 months after the start of the treatment. In that research – carried out on 120 patients who had severe and widespread periodontal disease (probing depth >6 mm and loss of marginal alveolar bone >30% for 50% or more teeth present on the dental arches) – before the start of the therapy, they measured some parameters, such as endothelial function based on the variation in brachial artery diameter during the flow (expressed in percentage, from the reference level to the maximum diameter reached in the interval between 45 and 75 seconds after blood pressure release), inflammation biomarkers, clotting markers and endothelial activation. Subsequently they compared them 1, 7, 30, 60 and 180 days after the start of the therapy. From this study all the patients suffering from systemic diseases or who had already suffered from acute or chronic infectious diseases or who had taken antibiotics up to three months before being recruited for the experimentation were excluded. All the patients received appropriate instructions about dental hygiene and the patients in the control group had tartar mechanically removed by supragingival scaling and polishing. The patients in the intensive care group underwent a full-mouth disinfection and supragingival and subgingival tartar removal, root planning – after administration of local anesthetic – , polishing, extraction of non savable teeth and positioning of minocycline microspheres in periodontal pockets.
FINDINGS OF M. TONETTI’S RESEARCH
A marked reduction of flow mediated expansion and a significant increase in reactive C protein, Interleukin-6, E-Selectin soluble endothelial activation marker, von Willebrand factor were already recorded in the intensive therapy group (61 patients) after just 24 hours from the start of the treatment. After 60 days and 180 days time, the parameters under examination inverted in the intensive therapy group with respect to the control group. The flow mediated expansion had increased and plasmatic levels of E-Selctin had decreased. The improvement of endothelial function observed after 6 months from the periodontal therapy is associated to a reduction in periodontal lesions and sites that bleed when probed.
The conclusion of this research is that an intensive mechanical periodontal treatment, not combined with systemic drug administration, causes an acute systemic inflammatory reaction for a short time and a temporary worsening of endothelial function. On the contrary, about 6 months after the therapy, an increase in oral health (decrease of periodontal indicators) goes along a recovery in endothelial function with increased elasticity of the arteries.
It is thus possible to state that there is a direct correlation between untreated periodontal disease, endothelial dysfunction and atherosclerosis with subsequent increase in the risks of heart disease and heart attack in patients suffering from periodontal disease. For these reasons, it is important to make an interdisciplinary cooperation having preventive aims among the heart specialist, the dental surgeon and the internist in order to make the patients aware of the existence of this correlation with cardiovascular diseases and treat them with the necessary periodontal treatments.
Amar S, Gokce N, Morgan S, Loukideli M, Van Dyke TE, Vita JA. Periodontal disease is associated with brachial artery endothelial dysfunctionand systemic inflammation.Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1245-9. Epub 2003 May 22.
Baltch A, Schaffer C, Hammer M, et al. Bacteremia following dental cleaning in patients with and without penicillin prophylaxis. Am Heart J 1982;104:1335.
Beck JD, Eke P, Heiss G, Madianos P, Couper D, Lin D, Moss K, Elter J,Offenbacher S. Periodontal disease and coronary heart disease: a reappraisal of the exposure.Circulation. 2005 Jul 5;112(1):19-24. Epub 2005 Jun 27.
Beck JD, Elter JR, Heiss G, Couper D, Mauriello SM, Offenbacher S. Relationship of periodontal disease to carotid artery intima-media wallthickness: the atherosclerosis risk in communities (ARIC) study.Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1816-22.
Beck JD, Elter JR, Heiss G, Couper D, Mauriello SM. Relationship of periodontal disease to carotid artery intima-media. Arterioscler thromb vasc biol 2001;21:1816-22.
Braunwald E. Shattuck lecture cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med 1997;337:1360-9.
Buhlin K, Gustafsson A, Pockley AG, Frostegård J, Klinge B. Risk factors for cardiovascular disease in patients with periodontitis.Eur Heart J. 2003 Dec;24(23):2099-107.
D’Aiuto F, Parkar M, Andreou G, Suvan J, Brett PM, Ready D, Tonetti MS. Periodontitis and systemic inflammation: control of the local infection isassociated with a reduction in serum inflammatory markers. J Dent Res. 2004 Feb;83(2):156-60.
Daly C, Mitchell D, Grossberg D, Highfield J, Stewart D. Bacteraemia following periodontal procedures. Aust Dent J 1997;42:77-80.
Debora C. Matthews, DDS, Periodontal Medicine: A New Paradigm. Dip. Perio., M.Sc.J Can Dent Assoc 2000; 66:488-9.
Denis F. Kinane , Marcello P. Riggio , Katie F. Walker. J Clin Periodontol 2005; 32: 708-713.
Dorn BR, Burks JN, Seifert KN, Progulske-Fox A. Invasion of endothelial and epithelial cells by strains of Porphyromonasgingivalis.FEMS Microbiol Lett. 2000 Jun 15;187(2):139-44.
Fong IW. Infections and their role in atherosclerotic vascular disease. Am Dental Assoc J Am Dent Assoc, 2002 Vol 133, No suppl_1, 7S-13S. Review
Forner, L., Larsen, T., Kilian, M. & Holmstrup, P. Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation. J Clin. Periodontol 2006; 33:401-7.
GC Armitage Periodontal infections and cardiovascular disease how strong is the association Oral Dis, 2000 Nov;6(6):335-50.
Guntheroth WG. How important are dental procedures as a cause of infective endocarditis? Am J Cardiol. 1984;54:797-801.
Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification of periodontal pathogens in atheromatous plaques.J Periodontol. 2000 Oct;71(10):1554-60.
Herzberg MC, Weyer MW. Dental plaque, platelets, and cardiovascular diseases. Ann Periodontol 98;3:151-160.
Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis.Circulation. 2002 Mar 5;105(9):1135-43. Review.
Loesche WL, Lopatin DE. Interactions between periodontal disease, medical diseases and immunity in the older individual. Periodontol 2000 1998;16:80-105.
Loos BG, Craandijk J, Hoek FJ, Wertheim-van Dillen PM, van der Velden U. Elevation of systemic markers related to cardiovascular diseases in theperipheral blood of periodontitis patients.J Periodontol. 2000 Oct;71(10):1528-34.
McFarlane CG, Reynolds JJ, Meikle MC. The release of interleukin-1ß, tumor necrosisfactor-a 1990;25: 207-214.
Mehta JL, Saldeen TG, Rand K. Interactive role of infection, inflammation and traditional risk factors inatherosclerosis and coronary artery disease. J Am Coll Cardiol. 1998 May;31(6):1217-25. Review.
MS Tonetti, FD’Aiuto, L Nibali, A Donald, C Storry Ann Donald, Clare Storry, B.Sc., Mohamed Parkar. Treatment of Periodontitis and Endothelial Function. N Engl J Med 2007;256:911-20. March 1, 2007, Number 9.
Nordoy A. Haemostatic factors in coronary heart disease.J Intern Med. 1993;233:377-383.
Scannapieco FA, Bush RB, Paju S. Associations between periodontal disease and risk for atherosclerosis,cardiovascular disease, and stroke. A systematic review.Ann Periodontol. 2003 Dec;8(1):38-53. Review.
Slade GD, Offenbacher S, Beck JD, Heiss G, Pankow JS. Acute phase inflammatory response to periodontal disease in the US population.J Dent Res. 2000 Jan;79(1):49-57.
Wilson PWF, Castelli WP, Kannel WB. Coronary risk prediction in adults: the Framingham Heart Study. Am J Cardiol. 1987;59:91–94
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