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DOI: 10.1055/s-0031-1273082
Dental Infection and Vascular Disease
Publication History
Publication Date:
31 March 2011 (online)
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ABSTRACT
Periodontitis is a chronic inflammatory response to bacterial plaque in which the anchoring bone and soft tissues supporting teeth are destroyed, resulting in tooth mobility and loss. Dental caries involves the spread of infection from the dentine to the vascular dental pulp and periapical bony tissues, before involvement of adjacent soft tissues and spreading sepsis. Several case-controlled, cross-sectional, and cohort studies report correlation between periodontitis and increased cardiovascular, cerebrovascular, and peripheral artery disease, as determined by clinical disease, angiography, ultrasonography, and reduced flow-mediated dilation. Some studies report a similar relationship of atherosclerosis with periapical infection and potentially also with coronal caries, and this review identifies the need to investigate these associations further. Smoking and cadmium exposure are epidemiologically confounding environmental risk factors shared by atherosclerosis and periodontitis. Further complicating epidemiological studies are the risk factors for both atherosclerosis and periodontitis, with which periodontitis appears to have separate positive feedback relationships. These include diabetes, increased plasma lipid levels, hypertension, and white blood cell count. Animal and human intervention studies provide some direct support of a causal role for periodontitis in atherosclerosis, and possible mechanisms include bacterial invasion of arteries, specific atherogenic properties of oral bacteria, the acute phase response, and cytokine polymorphisms.
KEYWORDS
Atherosclerosis - periodontal disease - periapical infection - epidemiology - intervention studies
REFERENCES
- 1 Cawson R A, Odell E W. Cawson's Essentials of Oral Pathology and Oral Medicine. 8th ed. Edinburgh, United Kingdom: Churchill Livingstone; 2008
- 2 Zoellner H, Hunter N. Perivascular hyaline deposits in inflamed gingival tissues. J Oral Pathol Med. 1989; 18 (6) 333-338
- 3 Short L L, Zoellner H, Hunter N. Association of amyloid P protein with pathology in periodontal tissues. J Oral Pathol Med. 1994; 23 (8) 354-357
- 4 Zoellner H, Hunter N. Chronic adult periodontitis and burst progression may reflect local neutrophil defects due to perivascular hyaline deposits. Med Hypotheses. 1991; 36 (4) 345-350
- 5 Zoellner H, Chapple C C, Hunter N. Microvasculature in gingivitis and chronic periodontitis: disruption of vascular networks with protracted inflammation. Microsc Res Tech. 2002; 56 (1) 15-31
- 6 Hunter N, Nicholls B, Srivastava M et al.. Reactive pocket epithelium in untreated chronic periodontal disease: possible derivation from developmental remnants of the enamel organ and root sheath. J Oral Pathol Med. 2001; 30 (3) 178-186
- 7 Mattila K J, Nieminen M S, Valtonen V V et al.. Association between dental health and acute myocardial infarction. BMJ. 1989; 298 (6676) 779-781
- 8 Syrjanen J, Peltola J, Valtonen V et al.. Dental infections in association with cerebral infarction in young and middle-aged men. J Intern Med. 1989; 225 (3) 179-184
- 9 Spodick D H. Inflammation and the onset of myocardial infarction. Ann Intern Med. 1985; 102 (5) 699-702
- 10 Nicholls A C, Thomas M. Coxsackie virus infection in acute myocardial infarction. Lancet. 1977; 1 (8017) 883-884
- 11 Griffiths P D, Hannington G, Booth J C. Coxsackie B virus infections and myocardial infarction. Results from a prospective, epidemiologically controlled study. Lancet. 1980; 1 (8183) 1387-1389
- 12 Saikku P, Leinonen M, Mattila K et al.. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet. 1988; 2 (8618) 983-986
- 13 Syrjanen J, Valtonen V V, Iivanainen M, Kaste M, Huttunen J K. Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients. Br Med J (Clin Res Ed). 1988; 296 (6630) 1156-1160
- 14 Emingil G, Buduneli E, Aliyev A, Akilli A, Atilla G. Association between periodontal disease and acute myocardial infarction. J Periodontol. 2000; 71 (12) 1882-1886
- 15 Persson G R, Ohlsson O, Pettersson T, Renvert S. Chronic periodontitis, a significant relationship with acute myocardial infarction. Eur Heart J. 2003; 24 (23) 2108-2115
- 16 Renvert S, Ohlsson O, Persson S, Lang N P, Persson G R. Analysis of periodontal risk profiles in adults with or without a history of myocardial infarction. J Clin Periodontol. 2004; 31 (1) 19-24
- 17 Andriankaja O M, Genco R J, Dorn J et al.. The use of different measurements and definitions of periodontal disease in the study of the association between periodontal disease and risk of myocardial infarction. J Periodontol. 2006; 77 (6) 1067-1073
- 18 Buhlin K, Gustafsson A, Ahnve S et al.. Oral health in women with coronary heart disease. J Periodontol. 2005; 76 (4) 544-550
- 19 Geismar K, Stoltze K, Sigurd B, Gyntelberg F, Holmstrup P. Periodontal disease and coronary heart disease. J Periodontol. 2006; 77 (9) 1547-1554
- 20 Briggs J E, McKeown P P, Crawford V L et al.. Angiographically confirmed coronary heart disease and periodontal disease in middle-aged males. J Periodontol. 2006; 77 (1) 95-102
- 21 Nonnenmacher C, Stelzel M, Susin C et al.. Periodontal microbiota in patients with coronary artery disease measured by real-time polymerase chain reaction: a case-control study. J Periodontol. 2007; 78 (9) 1724-1730
- 22 Berent R, Auer J, Schmid P et al.. Periodontal and coronary heart disease in patients undergoing coronary angiography. Metabolism. 2011; 60 (1) 127-133
- 23 Buhlin K, Gustafsson A, Hakansson J, Klinge B. Oral health and cardiovascular disease in Sweden. J Clin Periodontol. 2002; 29 (3) 254-259
- 24 Beck J, Garcia R, Heiss G, Vokonas P S, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol. 1996; 67 (10, Suppl) 1123-1137
- 25 Elter J R, Champagne C M, Offenbacher S, Beck J D. Relationship of periodontal disease and tooth loss to prevalence of coronary heart disease. J Periodontol. 2004; 75 (6) 782-790
- 26 Holmlund A, Holm G, Lind L. Severity of periodontal disease and number of remaining teeth are related to the prevalence of myocardial infarction and hypertension in a study based on 4,254 subjects. J Periodontol. 2006; 77 (7) 1173-1178
- 27 Gotsman I, Lotan C, Soskolne W A et al.. Periodontal destruction is associated with coronary artery disease and periodontal infection with acute coronary syndrome. J Periodontol. 2007; 78 (5) 849-858
- 28 Dorn J M, Genco R J, Grossi S G et al.. Periodontal disease and recurrent cardiovascular events in survivors of myocardial infarction (MI): the Western New York Acute MI Study. J Periodontol. 2010; 81 (4) 502-511
- 29 Beck J D, Offenbacher S. Systemic effects of periodontitis: epidemiology of periodontal disease and cardiovascular disease. J Periodontol. 2005; 76 (11, Suppl) 2089-2100
- 30 DeStefano F, Anda R F, Kahn H S, Williamson D F, Russell C M. Dental disease and risk of coronary heart disease and mortality. BMJ. 1993; 306 (6879) 688-691
- 31 Morrison H I, Ellison L F, Taylor G W. Periodontal disease and risk of fatal coronary heart and cerebrovascular diseases. J Cardiovasc Risk. 1999; 6 (1) 7-11
- 32 Mattila K J, Valtonen V V, Nieminen M, Huttunen J K. Dental infection and the risk of new coronary events: prospective study of patients with documented coronary artery disease. Clin Infect Dis. 1995; 20 (3) 588-592
- 33 Jansson L, Lavstedt S, Frithiof L. Relationship between oral health and mortality rate. J Clin Periodontol. 2002; 29 (11) 1029-1034
- 34 Ajwani S, Mattila K J, Tilvis R S, Ainamo A. Periodontal disease and mortality in an aged population. Spec Care Dentist. 2003; 23 (4) 125-130
- 35 Dietrich T, Jimenez M, Krall Kaye E A, Vokonas P S, Garcia R I. Age-dependent associations between chronic periodontitis/edentulism and risk of coronary heart disease. Circulation. 2008; 117 (13) 1668-1674
- 36 Blaizot A, Vergnes J N, Nuwwareh S, Amar J, Sixou M. Periodontal diseases and cardiovascular events: meta-analysis of observational studies. Int Dent J. 2009; 59 (4) 197-209
- 37 Grau A J, Buggle F, Ziegler C et al.. Association between acute cerebrovascular ischemia and chronic and recurrent infection. Stroke. 1997; 28 (9) 1724-1729
- 38 Grau A J, Becher H, Ziegler C M et al.. Periodontal disease as a risk factor for ischemic stroke. Stroke. 2004; 35 (2) 496-501
- 39 Pradeep A R, Hadge P, Arjun Raju P et al.. Periodontitis as a risk factor for cerebrovascular accident: a case-control study in the Indian population. J Periodontal Res. 2010; 45 (2) 223-228
- 40 Sim S J, Kim H D, Moon J Y et al.. Periodontitis and the risk for non-fatal stroke in Korean adults. J Periodontol. 2008; 79 (9) 1652-1658
- 41 Pradeep A R, Hadge P, Arjun Raju P et al.. Periodontitis as a risk factor for cerebrovascular accident: a case-control study in the Indian population. J Periodontal Res. 2010; 45 (2) 223-228
- 42 Loesche W J, Schork A, Terpenning M S et al.. The relationship between dental disease and cerebral vascular accident in elderly United States veterans. Ann Periodontol. 1998; 3 (1) 161-174
- 43 Elter J R, Offenbacher S, Toole J F, Beck J D. Relationship of periodontal disease and edentulism to stroke/TIA. J Dent Res. 2003; 82 (12) 998-1001
- 44 Wu T, Trevisan M, Genco R J et al.. Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study. Arch Intern Med. 2000; 160 (18) 2749-2755
- 45 Joshipura K J, Hung H C, Rimm E B, Willett W C, Ascherio A. Periodontal disease, tooth loss, and incidence of ischemic stroke. Stroke. 2003; 34 (1) 47-52
- 46 Abnet C C, Qiao Y L, Dawsey S M et al.. Tooth loss is associated with increased risk of total death and death from upper gastrointestinal cancer, heart disease, and stroke in a Chinese population-based cohort. Int J Epidemiol. 2005; 34 (2) 467-474
- 47 Jimenez M, Krall E A, Garcia R I, Vokonas P S, Dietrich T. Periodontitis and incidence of cerebrovascular disease in men. Ann Neurol. 2009; 66 (4) 505-512
- 48 Dorfer C E, Becher H, Ziegler C M et al.. The association of gingivitis and periodontitis with ischemic stroke. J Clin Periodontol. 2004; 31 (5) 396-401
- 49 Mendez M V, Scott T, LaMorte W et al.. An association between periodontal disease and peripheral vascular disease. Am J Surg. 1998; 176 (2) 153-157
- 50 Chen Y W, Umeda M, Nagasawa T et al.. Periodontitis may increase the risk of peripheral arterial disease. Eur J Vasc Endovasc Surg. 2008; 35 (2) 153-158
- 51 Mattila K J, Valle M S, Nieminen M S, Valtonen V V, Hietaniemi K L. Dental infections and coronary atherosclerosis. Atherosclerosis. 1993; 103 (2) 205-211
- 52 Cairo F, Castellani S, Gori A M et al.. Severe periodontitis in young adults is associated with sub-clinical atherosclerosis. J Clin Periodontol. 2008; 35 (6) 465-472
- 53 Beck J D, Elter J R, Heiss G et al.. Relationship of periodontal disease to carotid artery intima-media wall thickness: the atherosclerosis risk in communities (ARIC) study. Arterioscler Thromb Vasc Biol. 2001; 21 (11) 1816-1822
- 54 Desvarieux M, Demmer R T, Rundek T et al.. Relationship between periodontal disease, tooth loss, and carotid artery plaque: the Oral Infections and Vascular Disease Epidemiology Study (INVEST). Stroke. 2003; 34 (9) 2120-2125
- 55 Carallo C, Fortunato L, de Franceschi M S et al.. Periodontal disease and carotid atherosclerosis: are hemodynamic forces a link?. Atherosclerosis. 2010; 213 (1) 263-267
- 56 Friedlander A H, Sung E C, Chung E M, Garrett N R. Radiographic quantification of chronic dental infection and its relationship to the atherosclerotic process in the carotid arteries. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109 (4) 615-621
- 57 Cabrera C, Hakeberg M, Ahlqwist M et al.. Can the relation between tooth loss and chronic disease be explained by socio-economic status? A 24-year follow-up from the population study of women in Gothenburg, Sweden. Eur J Epidemiol. 2005; 20 (3) 229-236
- 58 Hung H C, Joshipura K J, Colditz G et al.. The association between tooth loss and coronary heart disease in men and women. J Public Health Dent. 2004; 64 (4) 209-215
- 59 Holmlund A, Holm G, Lind L. Number of teeth as a predictor of cardiovascular mortality in a cohort of 7,674 subjects followed for 12 years. J Periodontol. 2010; 81 (6) 870-876
- 60 Paunio K, Impivaara O, Tiekso J, Maki J. Missing teeth and ischaemic heart disease in men aged 45–64 years. Eur Heart J. 1993; 14 (Suppl K) 54-56
- 61 Pussinen P J, Jousilahti P, Alfthan G et al.. Antibodies to periodontal pathogens are associated with coronary heart disease. Arterioscler Thromb Vasc Biol. 2003; 23 (7) 1250-1254
- 62 Fure S, Zickert I. Incidence of tooth loss and dental caries in 60-, 70- and 80-year-old Swedish individuals. Community Dent Oral Epidemiol. 1997; 25 (2) 137-142
- 63 McCaul L K, Jenkins W M, Kay E J. The reasons for the extraction of various tooth types in Scotland: a 15-year follow up. J Dent. 2001; 29 (6) 401-407
- 64 Willershausen B, Kasaj A, Willershausen I et al.. Association between chronic dental infection and acute myocardial infarction. J Endod. 2009; 35 (5) 626-630
- 65 Bergstrom J. Cigarette smoking as risk factor in chronic periodontal disease. Community Dent Oral Epidemiol. 1989; 17 (5) 245-247
- 66 Amarasena N, Ekanayaka A N, Herath L, Miyazaki H. Tobacco use and oral hygiene as risk indicators for periodontitis. Community Dent Oral Epidemiol. 2002; 30 (2) 115-123
- 67 Bergstrom J, Eliasson S, Dock J. A 10-year prospective study of tobacco smoking and periodontal health. J Periodontol. 2000; 71 (8) 1338-1347
- 68 Okamoto Y, Tsuboi S, Suzuki S et al.. Effects of smoking and drinking habits on the incidence of periodontal disease and tooth loss among Japanese males: a 4-yr longitudinal study. J Periodontal Res. 2006; 41 (6) 560-566
- 69 Zee K Y. Smoking and periodontal disease. Aust Dent J. 2009; 54 (Suppl 1) S44-S50
- 70 Arora M, Weuve J, Schwartz J, Wright R O. Association of environmental cadmium exposure with periodontal disease in U.S. adults. Environ Health Perspect. 2009; 117 (5) 739-744
- 71 Soskolne W A, Klinger A. The relationship between periodontal diseases and diabetes: an overview. Ann Periodontol. 2001; 6 (1) 91-98
- 72 Mealey B L, Rose L F. Diabetes mellitus and inflammatory periodontal diseases. Curr Opin Endocrinol Diabetes Obes. 2008; 15 (2) 135-141
- 73 Santacroce L, Carlaio R G, Bottalico L. Does it make sense that diabetes is reciprocally associated with periodontal disease?. Endocr Metab Immune Disord Drug Targets. 2010; 10 (1) 57-70
- 74 Taylor G W, Loesche W J, Terpenning M S. Impact of oral diseases on systemic health in the elderly: diabetes mellitus and aspiration pneumonia. J Public Health Dent. 2000; 60 (4) 313-320
- 75 Rodrigues D C, Taba M J, Novaes A B, Souza S L, Grisi M F. Effect of non-surgical periodontal therapy on glycemic control in patients with type 2 diabetes mellitus. J Periodontol. 2003; 74 (9) 1361-1367
- 76 Inoue K, Kobayashi Y, Hanamura H, Toyokawa S. Association of periodontitis with increased white blood cell count and blood pressure. Blood Press. 2005; 14 (1) 53-58
- 77 Ogawa Y, Imaki M, Yoshida Y, Matsumoto M, Tanada S. Epidemiological study on the relationship between hypertension and dental disease in Japanese factory workers [in Japanese]. Sangyo Eiseigaku Zasshi. 1998; 40 (6) 235-240
- 78 Angeli F, Verdecchia P, Pellegrino C et al.. Association between periodontal disease and left ventricle mass in essential hypertension. Hypertension. 2003; 41 (3) 488-492
- 79 Renvert S, Pettersson T, Ohlsson O, Persson G R. Bacterial profile and burden of periodontal infection in subjects with a diagnosis of acute coronary syndrome. J Periodontol. 2006; 77 (7) 1110-1119
- 80 Persson G R, Pettersson T, Ohlsson O, Renvert S. High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis. J Clin Periodontol. 2005; 32 (3) 219-224
- 81 Bizzarro S, van der Velden U, Ten Heggeler J M et al.. Periodontitis is characterized by elevated PAI-1 activity. J Clin Periodontol. 2007; 34 (7) 574-580
- 82 Nibali L, D'Aiuto F, Griffiths G et al.. Severe periodontitis is associated with systemic inflammation and a dysmetabolic status: a case-control study. J Clin Periodontol. 2007; 34 (11) 931-937
- 83 Losche W, Karapetow F, Pohl A, Pohl C, Kocher T. Plasma lipid and blood glucose levels in patients with destructive periodontal disease. J Clin Periodontol. 2000; 27 (8) 537-541
- 84 Katz J, Flugelman M Y, Goldberg A, Heft M. Association between periodontal pockets and elevated cholesterol and low density lipoprotein cholesterol levels. J Periodontol. 2002; 73 (5) 494-500
- 85 Cutler C W, Shinedling E A, Nunn M et al.. Association between periodontitis and hyperlipidemia: cause or effect?. J Periodontol. 1999; 70 (12) 1429-1434
- 86 Ramirez-Tortosa M C, Quiles J L, Battino M et al.. Periodontitis is associated with altered plasma fatty acids and cardiovascular risk markers. Nutr Metab Cardiovasc Dis. 2010; 20 (2) 133-139
- 87 Morita M, Horiuchi M, Kinoshita Y, Yamamoto T, Watanabe T. Relationship between blood triglyceride levels and periodontal status. Community Dent Health. 2004; 21 (1) 32-36
- 88 Nakarai H, Yamashita A, Takagi M et al.. Periodontal disease and hypertriglyceridemia in Japanese subjects: potential association with enhanced lipolysis. Metabolism. 2010; September 1 (Epub ahead of print)
- 89 Buhlin K, Gustafsson A, Pockley A G, Frostegard J, Klinge B. Risk factors for cardiovascular disease in patients with periodontitis. Eur Heart J. 2003; 24 (23) 2099-2107
- 90 D'Aiuto F, Parkar M, Nibali L et al.. Periodontal infections cause changes in traditional and novel cardiovascular risk factors: results from a randomized controlled clinical trial. Am Heart J. 2006; 151 (5) 977-984
- 91 Ebersole J L, Cappelli D, Mott G et al.. Systemic manifestations of periodontitis in the non-human primate. J Periodontal Res. 1999; 34 (7) 358-362
- 92 Fentoglu O, Bozkurt F Y. The bi-directional relationship between periodontal disease and hyperlipidemia. Eur J Dent. 2008; 2 (2) 142-146
- 93 Taylor B A, Tofler G H, Carey H M et al.. Full-mouth tooth extraction lowers systemic inflammatory and thrombotic markers of cardiovascular risk. J Dent Res. 2006; 85 (1) 74-78
- 94 Piconi S, Trabattoni D, Luraghi C et al.. Treatment of periodontal disease results in improvements in endothelial dysfunction and reduction of the carotid intima-media thickness. FASEB J. 2009; 23 (4) 1196-1204
- 95 Acharya A, Bhavsar N, Jadav B, Parikh H. Cardioprotective effect of periodontal therapy in metabolic syndrome: a pilot study in Indian subjects. Metab Syndr Relat Disord. 2010; 8 (4) 335-341
- 96 Griffiths R, Barbour S. Lipoproteins and lipoprotein metabolism in periodontal disease. Clin Lipidol. 2010; 5 (3) 397-411
- 97 Dave S, Van Dyke T. The link between periodontal disease and cardiovascular disease is probably inflammation. Oral Dis. 2008; 14 (2) 95-101
- 98 Mattila K J, Asikainen S, Wolf J et al.. Age, dental infections, and coronary heart disease. J Dent Res. 2000; 79 (2) 756-760
- 99 Malthaner S C, Moore S, Mills M et al.. Investigation of the association between angiographically defined coronary artery disease and periodontal disease. J Periodontol. 2002; 73 (10) 1169-1176
- 100 Frisk F, Hakeberg M, Ahlqwist M, Bengtsson C. Endodontic variables and coronary heart disease. Acta Odontol Scand. 2003; 61 (5) 257-262
- 101 Tuominen R, Reunanen A, Paunio M, Paunio I, Aromaa A. Oral health indicators poorly predict coronary heart disease deaths. J Dent Res. 2003; 82 (9) 713-718
- 102 Hujoel P P, Drangsholt M, Spiekerman C, Derouen T A. Examining the link between coronary heart disease and the elimination of chronic dental infections. J Am Dent Assoc. 2001; 132 (7) 883-889
- 103 Hujoel P P, Drangsholt M, Spiekerman C, DeRouen T A. Pre-existing cardiovascular disease and periodontitis: a follow-up study. J Dent Res. 2002; 81 (3) 186-191
- 104 Joshipura K J, Rimm E B, Douglass C W et al.. Poor oral health and coronary heart disease. J Dent Res. 1996; 75 (9) 1631-1636
- 105 Howell T H, Ridker P M, Ajani U A, Hennekens C H, Christen W G. Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians. J Am Coll Cardiol. 2001; 37 (2) 445-450
- 106 Jain A, Batista Jr E L, Serhan C, Stahl G L, Van Dyke T E. Role for periodontitis in the progression of lipid deposition in an animal model. Infect Immun. 2003; 71 (10) 6012-6018
- 107 Serhan C N, Jain A, Marleau S et al.. Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous anti-inflammatory lipid mediators. J Immunol. 2003; 171 (12) 6856-6865
- 108 Li L, Messas E, Batista Jr E L, Levine R A, Amar S. Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model. Circulation. 2002; 105 (7) 861-867
- 109 Lalla E, Lamster I B, Hofmann M A et al.. Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol. 2003; 23 (8) 1405-1411
- 110 Gibson III F C, Hong C, Chou H H et al.. Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2004; 109 (22) 2801-2806
- 111 Koizumi Y, Kurita-Ochiai T, Oguchi S, Yamamoto M. Nasal immunization with Porphyromonas gingivalis outer membrane protein decreases P. gingivalis-induced atherosclerosis and inflammation in spontaneously hyperlipidemic mice. Infect Immun. 2008; 76 (7) 2958-2965
- 112 Miyamoto T, Yumoto H, Takahashi Y et al.. Pathogen-accelerated atherosclerosis occurs early after exposure and can be prevented via immunization. Infect Immun. 2006; 74 (2) 1376-1380
- 113 Tuomainen A M, Jauhiainen M, Kovanen P T et al.. Aggregatibacter actinomycetemcomitans induces MMP-9 expression and proatherogenic lipoprotein profile in apoE-deficient mice. Microb Pathog. 2008; 44 (2) 111-117
- 114 Zhang T, Kurita-Ochiai T, Hashizume T et al.. Aggregatibacter actinomycetemcomitans accelerates atherosclerosis with an increase in atherogenic factors in spontaneously hyperlipidemic mice. FEMS Immunol Med Microbiol. 2010; 59 (2) 143-151
- 115 Brodala N, Merricks E P, Bellinger D A et al.. Porphyromonas gingivalis bacteremia induces coronary and aortic atherosclerosis in normocholesterolemic and hypercholesterolemic pigs. Arterioscler Thromb Vasc Biol. 2005; 25 (7) 1446-1451
- 116 Koizumi Y, Kurita-Ochiai T, Oguchi S, Yamamoto M. Intranasal immunization with Porphyromonas gingivalis and atherosclerosis. Immunopharmacol Immunotoxicol. 2009; 31 (3) 352-357
- 117 Tonetti M S. Periodontitis and risk for atherosclerosis: an update on intervention trials. J Clin Periodontol. 2009; 36 (Suppl 10) 15-19
- 118 Koenig W. Inflammation and coronary heart disease: an overview. Cardiol Rev. 2001; 9 (1) 31-35
- 119 Sabatine M S, Morrow D A, Jablonski K A et al.. Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation. 2007; 115 (12) 1528-1536
- 120 Kampoli A M, Tousoulis D, Antoniades C, Siasos G, Stefanadis C. Biomarkers of premature atherosclerosis. Trends Mol Med. 2009; 15 (7) 323-332
- 121 Duivenvoorden R, de Groot E, Stroes E S, Kastelein J J. Surrogate markers in clinical trials–challenges and opportunities. Atherosclerosis. 2009; 206 (1) 8-16
- 122 Navab M, Reddy S T, Van Lenten B J, Anantharamaiah G M, Fogelman A M. The role of dysfunctional HDL in atherosclerosis. J Lipid Res. 2009; 50 (Suppl) S145-S149
- 123 Liapis C D, Avgerinos E D, Kadoglou N P, Kakisis J D. What a vascular surgeon should know and do about atherosclerotic risk factors. J Vasc Surg. 2009; 49 (5) 1348-1354
- 124 D'Aiuto F, Parkar M, Andreou G et al.. Periodontitis and atherogenesis: causal association or simple coincidence?. J Clin Periodontol. 2004; 31 (5) 402-411
- 125 D'Aiuto F, Parkar M, Andreou G et al.. Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers. J Dent Res. 2004; 83 (2) 156-160
- 126 Seinost G, Wimmer G, Skerget M et al.. Periodontal treatment improves endothelial dysfunction in patients with severe periodontitis. Am Heart J. 2005; 149 (6) 1050-1054
- 127 Paraskevas S, Huizinga J D, Loos B G. A systematic review and meta-analyses on C-reactive protein in relation to periodontitis. J Clin Periodontol. 2008; 35 (4) 277-290
- 128 Vidal F, Figueredo C M, Cordovil I, Fischer R G. Periodontal therapy reduces plasma levels of interleukin-6, C-reactive protein, and fibrinogen in patients with severe periodontitis and refractory arterial hypertension. J Periodontol. 2009; 80 (5) 786-791
- 129 El Fadl K A, Ragy N, El Batran M et al.. Periodontitis and cardiovascular disease: floss and reduce a potential risk factor for CVD. Angiology. 2011; 62 (1) 62-67
- 130 D'Aiuto F, Nibali L, Parkar M, Suvan J, Tonetti M S. Short-term effects of intensive periodontal therapy on serum inflammatory markers and cholesterol. J Dent Res. 2005; 84 (3) 269-273
- 131 Elter J R, Hinderliter A L, Offenbacher S et al.. The effects of periodontal therapy on vascular endothelial function: a pilot trial. Am Heart J. 2006; 151 (1) 47
- 132 Taylor B, Tofler G, Morel-Kopp M C et al.. The effect of initial treatment of periodontitis on systemic markers of inflammation and cardiovascular risk: a randomized controlled trial. Eur J Oral Sci. 2010; 118 (4) 350-356
- 133 Sinisalo J, Paronen J, Mattila K J et al.. Relation of inflammation to vascular function in patients with coronary heart disease. Atherosclerosis. 2000; 149 (2) 403-411
- 134 Amar S, Gokce N, Morgan S et al.. Periodontal disease is associated with brachial artery endothelial dysfunction and systemic inflammation. Arterioscler Thromb Vasc Biol. 2003; 23 (7) 1245-1249
- 135 Mercanoglu F, Oflaz H, Oz O et al.. Endothelial dysfunction in patients with chronic periodontitis and its improvement after initial periodontal therapy. J Periodontol. 2004; 75 (12) 1694-1700
- 136 Blum A, Kryuger K, Mashiach Eizenberg M et al.. Periodontal care may improve endothelial function. Eur J Intern Med. 2007; 18 (4) 295-298
- 137 Tonetti M S, D'Aiuto F, Nibali L et al.. Treatment of periodontitis and endothelial function. N Engl J Med. 2007; 356 (9) 911-920
- 138 Beck J D, Couper D J, Falkner K L et al.. The Periodontitis and Vascular Events (PAVE) pilot study: adverse events. J Periodontol. 2008; 79 (1) 90-96
- 139 Offenbacher S, Beck J D, Moss K et al.. Results from the Periodontitis and Vascular Events (PAVE) study: a pilot multicentered, randomized, controlled trial to study effects of periodontal therapy in a secondary prevention model of cardiovascular disease. J Periodontol. 2009; 80 (2) 190-201
- 140 Zoellner H, Hunter N. Vascular expansion in chronic periodontitis. J Oral Pathol Med. 1991; 20 (9) 433-437
- 141 Haraszthy V I, Zambon J J, Trevisan M, Zeid M, Genco R J. Identification of periodontal pathogens in atheromatous plaques. J Periodontol. 2000; 71 (10) 1554-1560
- 142 Gaetti-Jardim Jr E, Marcelino S L, Feitosa A C, Romito G A, Avila-Campos M J. Quantitative detection of periodontopathic bacteria in atherosclerotic plaques from coronary arteries. J Med Microbiol. 2009; 58 (Pt 12) 1568-1575
- 143 Nakano K, Inaba H, Nomura R et al.. Detection of cariogenic Streptococcus mutans in extirpated heart valve and atheromatous plaque specimens. J Clin Microbiol. 2006; 44 (9) 3313-3317
- 144 Fiehn N E, Larsen T, Christiansen N, Holmstrup P, Schroeder T V. Identification of periodontal pathogens in atherosclerotic vessels. J Periodontol. 2005; 76 (5) 731-736
- 145 Mahendra J, Mahendra L, Kurian V M, Jaishankar K, Mythilli R. 16S rRNA-based detection of oral pathogens in coronary atherosclerotic plaque. Indian J Dent Res. 2010; 21 (2) 248-252
- 146 Pussinen P J, Alfthan G, Jousilahti P, Paju S, Tuomilehto J. Systemic exposure to Porphyromonas gingivalis predicts incident stroke. Atherosclerosis. 2007; 193 (1) 222-228
- 147 Pussinen P J, Alfthan G, Tuomilehto J, Asikainen S, Jousilahti P. High serum antibody levels to Porphyromonas gingivalis predict myocardial infarction. Eur J Cardiovasc Prev Rehabil. 2004; 11 (5) 408-411
- 148 Bohnstedt S, Cullinan M P, Ford P J et al.. High antibody levels to P. gingivalis in cardiovascular disease. J Dent Res. 2010; 89 (9) 938-942
- 149 Pussinen P J, Nyyssonen K, Alfthan G et al.. Serum antibody levels to Actinobacillus actinomycetemcomitans predict the risk for coronary heart disease. Arterioscler Thromb Vasc Biol. 2005; 25 (4) 833-838
- 150 Pussinen P J, Alfthan G, Rissanen H et al.. Antibodies to periodontal pathogens and stroke risk. Stroke. 2004; 35 (9) 2020-2023
- 151 Nakano K, Inaba H, Nomura R et al.. Distribution of Porphyromonas gingivalis fimA genotypes in cardiovascular specimens from Japanese patients. Oral Microbiol Immunol. 2008; 23 (2) 170-172
- 152 Herzberg M C, Nobbs A, Tao L et al.. Oral streptococci and cardiovascular disease: searching for the platelet aggregation-associated protein gene and mechanisms of Streptococcus sanguis-induced thrombosis. J Periodontol. 2005; 76 (11, Suppl) 2101-2105
- 153 Bizzarro S, Nicu E A, van der Velden U, Laine M L, Loos B G. Association of serum Immunoglobulins G (IgG) levels against two periodontal pathogens and a prothrombotic state: a clinical pilot study. Thromb J. 2010; 8 (1) 16
- 154 Kallio K A, Buhlin K, Jauhiainen M et al.. Lipopolysaccharide associates with pro-atherogenic lipoproteins in periodontitis patients. Innate Immun. 2008; 14 (4) 247-253
- 155 Roth G A, Ankersmit H J, Brown V B et al.. Porphyromonas gingivalis infection and cell death in human aortic endothelial cells. FEMS Microbiol Lett. 2007; 272 (1) 106-113
- 156 Maekawa T, Takahashi N, Honda T et al.. Porphyromonas gingivalis antigens and interleukin-6 stimulate the production of monocyte chemoattractant protein-1 via the upregulation of early growth response-1 transcription in human coronary artery endothelial cells. J Vasc Res. 2010; 47 (4) 346-354
- 157 Roth G A, Moser B, Roth-Walter F et al.. Infection with a periodontal pathogen increases mononuclear cell adhesion to human aortic endothelial cells. Atherosclerosis. 2007; 190 (2) 271-281
- 158 Roth G A, Moser B, Huang S J et al.. Infection with a periodontal pathogen induces procoagulant effects in human aortic endothelial cells. J Thromb Haemost. 2006; 4 (10) 2256-2261
- 159 Naito M, Sakai E, Shi Y et al.. Porphyromonas gingivalis-induced platelet aggregation in plasma depends on Hgp44 adhesin but not Rgp proteinase. Mol Microbiol. 2006; 59 (1) 152-167
- 160 Pejcic A, Kesic L J, Milasin J. C-reactive protein as a systemic marker of inflammation in periodontitis. Eur J Clin Microbiol Infect Dis. 2010; November 6 (Epub ahead of print)
- 161 Desvarieux M, Demmer R T, Jacobs Jr D R et al.. Periodontal bacteria and hypertension: the oral infections and vascular disease epidemiology study (INVEST). J Hypertens. 2010; 28 (7) 1413-1421
- 162 Kumar V, Abbas A K, Fausto N. Robbins and Cotran Pathologic Basis of Disease. 7th ed. Philadelphia, PA: WB Saunders; 2005: 1552
- 163 Higashi Y, Goto C, Jitsuiki D et al.. Periodontal infection is associated with endothelial dysfunction in healthy subjects and hypertensive patients. Hypertension. 2008; 51 (2) 446-453
- 164 Tsioufis C, Thomopoulos C, Soldatos N et al.. The conjoint detrimental effect of chronic periodontal disease and systemic inflammation on asymmetric dimethyl-arginine in untreated hypertensive subjects. Atherosclerosis. 2010; 208 (1) 258-263
- 165 Malali E, Basar I, Emekli-Alturfan E et al.. Levels of C-reactive protein and protein c in periodontitis patients with and without cardiovascular disease. Pathophysiol Haemost Thromb. 2010; 37 (1) 49-54
- 166 Yudkin J S, Kumari M, Humphries S E, Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?. Atherosclerosis. 2000; 148 (2) 209-214
- 167 Moutsopoulos N M, Madianos P N. Low-grade inflammation in chronic infectious diseases: paradigm of periodontal infections. Ann N Y Acad Sci. 2006; 1088 251-264
- 168 Zoellner H, Cebon J, Layton J E, Stanton H, Hamilton J A. Contrasting effects of interleukin-4 on colony-stimulating factor and interleukin-6 synthesis by vascular endothelial cells. Lymphokine Cytokine Res. 1993; 12 (2) 93-99
- 169 Matsuki Y, Yamamoto T, Hara K. Detection of inflammatory cytokine messenger RNA (mRNA)-expressing cells in human inflamed gingiva by combined in situ hybridization and immunohistochemistry. Immunology. 1992; 76 (1) 42-47
- 170 Takahashi K, Takashiba S, Nagai A et al.. Assessment of interleukin-6 in the pathogenesis of periodontal disease. J Periodontol. 1994; 65 (2) 147-153
- 171 Zoellner H F, Hunter N. High endothelial-like venules in chronically inflamed periodontal tissues exchange polymorphs. J Pathol. 1989; 159 (4) 301-310
- 172 Zorio E, Gilabert-Estelles J, Espana F et al.. Fibrinolysis: the key to new pathogenetic mechanisms. Curr Med Chem. 2008; 15 (9) 923-929
- 173 Paraskevas K I, Baker D M, Vrentzos G E, Mikhailidis D P. The role of fibrinogen and fibrinolysis in peripheral arterial disease. Thromb Res. 2008; 122 (1) 1-12
- 174 D'Aiuto F, Parkar M, Brett P M, Ready D, Tonetti M S. Gene polymorphisms in pro-inflammatory cytokines are associated with systemic inflammation in patients with severe periodontal infections. Cytokine. 2004; 28 (1) 29-34
- 175 Goteiner D, Ashmen R, Lehrman N, Janal M N, Eskin B. Presence and significance of interleukin-1 polymorphism in patients who present with acute coronary syndrome, angina, and chronic periodontitis: an epidemiologic pilot study. J Periodontol. 2008; 79 (1) 138-143
A/Professor Hans Zoellner
The Cellular and Molecular Pathology Research Unit, Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, The University of Sydney, Westmead Centre for Oral Health, Westmead Hospital, Westmead
NSW 2145, Australia
Email: hans.zoellner@sydney.edu.au