Our mission is to become a worldwide reference for education in the field for all professionals involved in the process to dissemintate knowledge & skills of Acute Cardiovascular Care
Our mission is to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular imaging in Europe.
Our mission: To promote excellence in research, practice, education and policy in cardiovascular health, primary and secondary prevention.
Our goal is to reduce the burden in cardiovascular disease in Europe through percutaneous cardiovascular interventions.
Our Mission is "to improve the quality of life of the population by reducing the impact of cardiac rhythm disturbances and reduce sudden cardiac death"
To improve quality of life and logevity, through better prevention, diagnosis and treatment of heart failure, including the establishment of networks for its management, education and research.
Working Groups goals is to stimulate and disseminate scientific knowledge in different fields of cardiology.
ESC Councils goal is to share knowledge among medical professionals practising in specific cardiology domains.
OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Prof. Michael Bohm
Dr. Nicolas Werner
The VA Normative Aging and Dental Longitudinal Studies in Boston followed 1200 men for up to 35 years and gave clear evidence of an association between chronic periodontitis and the risk of coronary heart disease independent of classical risk factors. We also know that periodontitis causes endothelial dysfunction together with systemic inflammation and endothelial function can be improved after successful periodontal treatment - however no true causal relation between periodontitis and vascular disease has been evidenced. Regular dental care with treatment of periodontitis using local dental and antibiotic therapy seems advisable in patients at risk for atherosclerotic disease, because poor oral health and the presence of periodontitis may negatively affect the blood vessel wall.
Inflammation is an important pace maker of atherogenesis2, which involves the diseased cells of the vessel wall such as endothelial cells and smooth muscle cells and circulating inflammatory cells. Adhesion and invasion of T cells and monocytes leads to an accelerated inflammatory reaction in the vessel wall and enhances progression of atherosclerosis.
Besides these processes, several other effects such as lipid deposition and pathological proliferation and migration of smooth muscle cells contribute to the atherosclerotic process. Destabilisation of plaques with subsequent plaque rupture initiates a cascade of pro-coagulatory events and may lead to the occlusion of the diseased vessel and to cardiovascular events such as myocardial infarction and stroke.
Periodontitis is thought to be caused by local infection with periodontal pathogens and subsequent local inflammation.
a) The risk factors for periodontis are similar to those of atherosclerotic disease
Abnormal host responses contribute to a more rapid disease progression in some patients. The prevalence of periodontal disease is high and this disease is more common with cigarette smoking, obesity, and diabetes mellitus – risk factors that also predispose to atherosclerotic disease.
b) There is an association between the presence of periodontitis and coronary artery disease and an increased cardiovascular event rate
Epidemiological studies demonstrated an association between the presence of periodontitis and coronary artery disease and an increased cardiovascular event rate, respectively 3-7. This association appears to depend on the severity of periodontal disease but is independent of the presence of traditional cardiovascular risk factors. However, other studies did not find significant associations after adjustment for important confounders 7.
c) Periodontitis causes endothelial dysfunction together with systemic inflammation
The degree of chronic inflammation in the oral cavity during periodontitis is sufficient to induce systemic inflammatory reactions by stimulation of humoral and cell-mediated pathways 6,9-11. As outlined above, inflammatory processes are crucial in the pathogenesis of endothelial dysfunction and atherosclerosis. Indeed, recent clinical investigations have demonstrated that severe periodontitis causes endothelial dysfunction together with systemic inflammation.
d) Endothelial function can be improved after successful periodontal treatment
Importantly, endothelial function was improved after successful periodontal treatment 12-15. In patients without atherosclerotic disease, severe periodontitis was associated with an increased intima/media thickness of the common carotid arteries, a surrogate parameter of early atherogenesis and in patients with essential hypertension, an association between severity of periodontitis and left ventricular mass was recently suggested 9,16.
e) A correlation was demonstrated between chronic periodontitis and incidence of coronary heart disease
In a current publication by Dietrich et al., the association between periodontitis and risk of coronary heart disease was further investigated in 1203 men of the VA Normative Aging and Dental Longitudinal Studies 17. These men were followed up with triennial medical and dental examinations for up to 35 years. A clear correlation was demonstrated between chronic periodontitis in these initially healthy men with incidence of coronary heart disease, independent of established cardiovascular risk factors. Interestingly, this close association was only present in men <60 years of age.
f) The mechanisms leading to vascular damage by periodontal disease are less clear
The mechanisms leading to vascular damage by periodontal disease are less clear. Periodontal pathogens seem to play an important role in this context. Antibodies to these pathogens are associated with coronary artery disease, the periodontal pathogen burden correlates with the presence of coronary artery disease, and bacterial DNA was found in atherosclerotic plaques of coronary arteries 18-22.
Oral and intravenous infection with the periodontal pathogen Porphyromonas gingivalis (P.g.) accelerated atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice, an established mouse model of atherosclerosis, and in normocholesterolemic and hypercholesterolemic pigs 23-26. Infection of human aortic endothelial cells with P.g. induced an up-regulation of the adhesion molecules VCAM-1, ICAM-1, and E-selectin and of the pro-inflammatory cytokines interleukin-6 and interleukin-8 27.
In addition, it was demonstrated that P.g.-induced pathologies were mediated through activation of toll-like receptors TLR-2 and TLR-4, receptors of the innate immune system that seem to be involved in the pathogenesis of atherosclerosis 28-33.
a) Act on etiologic factors
Periodontitis shares several common etiologic factors e.g. smoking, diabetes, hypertension but also low social class and unfavourable health care with coronary heart disease (CHD). In the VA Normative Aging and Dental Longitudinal Studies mentioned above 1200 men were followed for up to 35 years and give clear evidence for an association between chronic periodontitis and the risk of coronary heart disease independent of classical risk factors 17.
However, until today, no convincing evidence has been presented demonstrating a true causal relation between periodontitis and vascular disease. There is a definite need for prospective studies assessing periodontal disease and clinical endpoints of cardiovascular disease.
b) Patients at risk for atherosclerotic disease especially need regular dental care and statins, perhaps.
Until this data is present, health care providers should keep in mind that poor oral health and the presence of periodontitis may negatively affect the blood vessel wall. Regular dental care with treatment of periodontitis using local dental and antibiotic therapy 34 seems advisable in patients at risk for atherosclerotic disease. Interestingly, first data suggests that patients on statin medication exhibit fewer signs of periodontal inflammatory injury than subjects without statin therapy 35.
Figure : Periodontis and Atherosclerosis : Process and treatment
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
1. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999;340:115-126. 2. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135-1143. 3. Arbes SJ, Jr., Slade GD, Beck JD. Association between extent of periodontal attachment loss and self-reported history of heart attack: an analysis of NHANES III data. J Dent Res. 1999;78:1777-1782. 4. Behle JH, Papapanou PN. Periodontal infections and atherosclerotic vascular disease: an update. Int Dent J. 2006;56:256-262. 5. Emingil G, Buduneli E, Aliyev A, Akilli A, Atilla G. Association between periodontal disease and acute myocardial infarction. J Periodontol. 2000;71:1882-1886. 6. Haynes WG, Stanford C. Periodontal disease and atherosclerosis: from dental to arterial plaque. Arterioscler Thromb Vasc Biol. 2003;23:1309-1311. 7. Hujoel PP, Drangsholt M, Spiekerman C, DeRouen TA. Periodontal disease and coronary heart disease risk. JAMA. 2000;284:1406-1410. 8. Pussinen PJ, Mattila K. Periodontal infections and atherosclerosis: mere associations? Curr Opin Lipidol. 2004;15:583-588. 9. Leivadaros E, van d, V, Bizzarro S, ten Heggeler JM, Gerdes VE, Hoek FJ, Nagy TO, Scholma J, Bakker SJ, Gans RO, ten Cate H, Loos BG. A pilot study into measurements of markers of atherosclerosis in periodontitis. J Periodontol. 2005;76:121-128. 10. 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;79:49-57. 11. Zheng P, Chen H, Shi S, Jepsen S, Eberhard J. Periodontal parameters and platelet-activating factor levels in serum and gingival crevicular fluid in a Chinese population. J Clin Periodontol. 2006;33:797-802. 12. Elter JR, Hinderliter AL, Offenbacher S, Beck JD, Caughey M, Brodala N, Madianos PN. The effects of periodontal therapy on vascular endothelial function: a pilot trial. Am Heart J. 2006;151:47. 13. Mercanoglu F, Oflaz H, Oz O, Gokbuget AY, Genchellac H, Sezer M, Nisanci Y, Umman S. Endothelial dysfunction in patients with chronic periodontitis and its improvement after initial periodontal therapy. J Periodontol. 2004;75:1694-1700. 14. Seinost G, Wimmer G, Skerget M, Thaller E, Brodmann M, Gasser R, Bratschko RO, Pilger E. Periodontal treatment improves endothelial dysfunction in patients with severe periodontitis. Am Heart J. 2005;149:1050-1054. 15. Tonetti MS, D'Aiuto F, Nibali L, Donald A, Storry C, Parkar M, Suvan J, Hingorani AD, Vallance P, Deanfield J. Treatment of periodontitis and endothelial function. N Engl J Med. 2007;356:911-920. 16. Angeli F, Verdecchia P, Pellegrino C, Pellegrino RG, Pellegrino G, Prosciutti L, Giannoni C, Cianetti S, Bentivoglio M. Association between periodontal disease and left ventricle mass in essential hypertension. Hypertension. 2003;41:488-492. 17. Dietrich T, Jimenez M, Krall Kaye EA, Vokonas PS, Garcia RI. Age-dependent associations between chronic periodontitis/edentulism and risk of coronary heart disease. Circulation. 2008;117:1668-1674. 18. Chun YH, Chun KR, Olguin D, Wang HL. Biological foundation for periodontitis as a potential risk factor for atherosclerosis. J Periodontal Res. 2005;40:87-95. 19. Fiehn NE, Larsen T, Christiansen N, Holmstrup P, Schroeder TV. Identification of periodontal pathogens in atherosclerotic vessels. J Periodontol. 2005;76:731-736. 20. Pucar A, Milasin J, Lekovic V, Vukadinovic M, Ristic M, Putnik S, Kenney EB. Correlation between atherosclerosis and periodontal putative pathogenic bacterial infections in coronary and internal mammary arteries. J Periodontol. 2007;78:677-682. 21. Pussinen PJ, Jousilahti P, Alfthan G, Palosuo T, Asikainen S, Salomaa V. Antibodies to periodontal pathogens are associated with coronary heart disease. Arterioscler Thromb Vasc Biol. 2003;23:1250-1254. 22. Spahr A, Klein E, Khuseyinova N, Boeckh C, Muche R, Kunze M, Rothenbacher D, Pezeshki G, Hoffmeister A, Koenig W. Periodontal infections and coronary heart disease: role of periodontal bacteria and importance of total pathogen burden in the Coronary Event and Periodontal Disease (CORODONT) study. Arch Intern Med. 2006;166:554-559. 23. Brodala N, Merricks EP, Bellinger DA, Damrongsri D, Offenbacher S, Beck J, Madianos P, Sotres D, Chang YL, Koch G, Nichols TC. Porphyromonas gingivalis bacteremia induces coronary and aortic atherosclerosis in normocholesterolemic and hypercholesterolemic pigs. Arterioscler Thromb Vasc Biol. 2005;25:1446-1451. 24. Gibson FC, III, Hong C, Chou HH, Yumoto H, Chen J, Lien E, Wong J, Genco CA. Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2004;109:2801-2806. 25. Lalla E, Lamster IB, Hofmann MA, Bucciarelli L, Jerud AP, Tucker S, Lu Y, Papapanou PN, Schmidt AM. Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol. 2003;23:1405-1411. 26. Li L, Messas E, Batista EL, Jr., Levine RA, Amar S. Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model. Circulation. 2002;105:861-867. 27. Chou HH, Yumoto H, Davey M, Takahashi Y, Miyamoto T, Gibson FC, III, Genco CA. Porphyromonas gingivalis fimbria-dependent activation of inflammatory genes in human aortic endothelial cells. Infect Immun. 2005;73:5367-5378. 28. Gibson FC, III, Hong C, Chou HH, Yumoto H, Chen J, Lien E, Wong J, Genco CA. Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2004;109:2801-2806. 29. Hajishengallis G, Sharma A, Russell MW, Genco RJ. Interactions of oral pathogens with toll-like receptors: possible role in atherosclerosis. Ann Periodontol. 2002;7:72-78. 30. Harokopakis E, Albzreh MH, Martin MH, Hajishengallis G. TLR2 transmodulates monocyte adhesion and transmigration via Rac1- and PI3K-mediated inside-out signaling in response to Porphyromonas gingivalis fimbriae. J Immunol. 2006;176:7645-7656. 31. Li H, Sun B. Toll-like receptor 4 in atherosclerosis. J Cell Mol Med. 2007;11:88-95. 32. Mullick AE, Tobias PS, Curtiss LK. Modulation of atherosclerosis in mice by Toll-like receptor 2. J Clin Invest. 2005;115:3149-3156. 33. Xu XH, Shah PK, Faure E, Equils O, Thomas L, Fishbein MC, Luthringer D, Xu XP, Rajavashisth TB, Yano J, Kaul S, Arditi M. Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL. Circulation. 2001;104:3103-3108. 34. Teles RP, Haffajee AD, Socransky SS. Microbiological goals of periodontal therapy. Periodontol 2000. 2006;42:180-218. 35. Lindy O, Suomalainen K, Makela M, Lindy S. Statin use is associated with fewer periodontal lesions: A retrospective study. BMC Oral Health. 2008;8:16. epub ahead of print.
Above Pubmed references are available upon request by sending an e-mail to the e-journal of Cardiology Practice.
Dr. N. Werner and Prof. M. Böhm 1Bonn and 2Homburg-Saar, Germany 2Nucleus member of Heart Failure Association of the ESC.