Periodontal Disease and Atherosclerosis
2003; Lippincott Williams & Wilkins; Volume: 23; Issue: 8 Linguagem: Inglês
10.1161/01.atv.0000087144.24654.71
ISSN1524-4636
AutoresWilliam G. Haynes, Clark M. Stanford,
Tópico(s)Oral Health Pathology and Treatment
ResumoHomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 23, No. 8Periodontal Disease and Atherosclerosis Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBPeriodontal Disease and AtherosclerosisFrom Dental to Arterial Plaque William G. Haynes and Clark Stanford William G. HaynesWilliam G. Haynes From the General Clinical Research Center, the Department of Internal Medicine (W.G.H.), Carver College of Medicine; and the Dows Institute for Dental Research (C.S.), College of Dentistry, University of Iowa, Iowa City, Iowa. and Clark StanfordClark Stanford From the General Clinical Research Center, the Department of Internal Medicine (W.G.H.), Carver College of Medicine; and the Dows Institute for Dental Research (C.S.), College of Dentistry, University of Iowa, Iowa City, Iowa. Originally published1 Aug 2003https://doi.org/10.1161/01.ATV.0000087144.24654.71Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1309–1311The conventional risk factors for atherosclerosis are well understood, but they can account for only about 50% to 70% of atherosclerotic events in the general population. Many other putative risk factors for atherosclerosis have been proposed, including traits related to obesity, inflammation, and infection. Periodontal disease is a candidate risk factor that shares many of these related traits. The periodontal diseases reflect a spectrum of oral pathology from gingivitis (gum inflammation) to severe periodontitis (progressive loss of gum attachment) with alveolar bone and tooth loss.See page 1405The pathogenesis of periodontal disease is thought to be due to accumulation of dental plaque (bacteria in subgingival biofilms) with consequent mucosal infection and inflammation. Abnormal host responses, with upregulation of matrix metalloproteinases, contribute to a more rapid disease progression in some patients. Periodontal disease is more common with cigarette smoking, obesity, and diabetes, and it affects about 75% of the adult population in the United States, with about 20% to 30% of adults having severe forms.1,2 Increasing evidence over the past decade suggests a link between periodontal disease and atherosclerosis.Multiple cross-sectional studies have demonstrated a higher incidence of atherosclerotic complications in patients with periodontal disease.3–6 In the NHANES III cohort, severe periodontal disease was associated with an almost 4-fold higher incidence of myocardial infarction than found in patients without periodontal disease.6 In cross-sectional studies, the cardiovascular risk associated with periodontal disease appears dependent on severity of the disease, and it is independent of conventional risk factors (including smoking, poverty, diabetes, and body mass index).7 One problem with cross-sectional and case-control studies is that they do not tell us whether a disease is a cause or a consequence of another condition. For example, it is possible that atherosclerosis might exacerbate periodontal disease, by causing a systemic inflammatory response or even through subclinical ischemia. Longitudinal cohort studies permit this possibility to be tested.As is often the case with novel risk factors, the results of longitudinal studies have not been as uniformly or strongly positive as cross-sectional ones. However, several prospective studies have suggested a 1.5- to 2.5-fold increased risk of developing complications of atherosclerosis among patients with periodontal disease at baseline.8–11 Two large prospective studies failed to find an association between periodontal disease and atherosclerosis after adjusting for other risk factors.12,13 These inconsistent prospective studies may relate to lack of discrimination between mild and severe periodontal disease; the development of periodontal disease in patients free of it at baseline or confounding genetic variables, such interleukin genotype. These factors would tend to reduce the strength of any association. At the very least, the prospective studies demonstrate that periodontal disease precedes atherosclerosis. Overall, the observational studies support a strong link with atherosclerosis, but cannot prove causation.There are several possible explanations for the association between periodontal disease and complications of atherosclerosis. First, it may merely reflect confounding by common risk factors that cause both periodontal disease and atherosclerosis, such as smoking, obesity, and diabetes. All of the observational studies have adjusted statistically for these risk factors, though such adjustments can be problematic when large differences in risk factor burden exist between groups. Additionally, there may be as yet unknown shared risk factors that cannot be taken into account.Second, the association may reflect an individual propensity to develop an exuberant inflammatory response to intrinsic (age, sex, genes) or extrinsic stimuli (diet, smoking, etc) that then predisposes to both periodontal disease and atherosclerosis.Third, the presence of an inflammatory focus in the oral cavity may potentiate the atherosclerotic process by stimulation of humoral and cell-mediated inflammatory pathways. The degree of inflammation in periodontal disease is clearly sufficient to cause a systemic inflammatory response, as evidenced by increases in C-reactive protein.14,15 Cross-reactivity of antibodies to periodontal pathogens with antigens present in platelets or endothelial cells might be an additional pro-inflammatory mechanism.16Fourth, the presence of periodontal infection may lead to brief episodes of bacteremia with inoculation of atherosclerotic plaques by periodontal pathogens such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Bacteroides forsythus. Subsequent growth of these bacteria would cause inflammation and plaque instability. Indeed, there is evidence using immunostaining and polymerase chain reaction for bacterial rDNA that these pathogens are present in 18% to 30% of carotid atheromas.17,18 Identifying the true nature of the relationship between periodontal disease and atherosclerosis will be crucial so that appropriate screening and treatment recommendations can be made. Three new articles the July issue and in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology shed new light on the role of periodontal disease in atherosclerosis.19–21Pussinen and colleagues21 report that antibodies to select periodontal pathogens are associated with coronary heart disease. These investigators developed multiserotype ELISAs for detection of IgG antibodies to 3 strains of P. gingivalis and 6 strains of A. actinomycetemcomitans. These antibody tests have sensitivity of 70% and specificity of 90% for clinically and radiologically diagnosed periodontitis. In a sample of 1163 middle-aged men, combined antibody titers were associated with coronary heart disease (CHD).21 Because edentulous status was strongly associated with coronary disease, the investigators analyzed dentate and edentulous subjects separately. Though edentulous subjects tended to have lower antibody titers than dentate ones, high antibody titers (more than 3 standard deviations above the mean for periodontally healthy subjects) were associated with a 2- to 3-fold higher incidence of coronary heart disease. Similar findings were observed in dentate subjects, with high antibody titers associated with an odds ratio for CHD of 1.5, even after adjustment for conventional risk factors. Importantly, only antibodies to P. gingivalis were associated with CHD.This interesting study has several implications. First it confirms that edentulous status is a marker for atherosclerotic coronary disease. Caries was not associated with CHD, suggesting that it is periodontal disease that causes loss of teeth in these patients. However, because loss or removal of teeth appears to attenuate periodontal infection/inflammation (as evidenced by lower antibody titers), edentulous patients should be excluded or analyzed separately in these studies. Second, this study, using different methodology (serology) and in a larger sample, confirms previous work22 that periodontal infection is associated with coronary disease. Third, the apparent specificity of antibodies to P. gingivalis for incident CHD would support the hypothesis that infection with, or the host response to, this particular bacteria is particularly deleterious in terms of atherosclerotic complications. This possibility is supported by another of the studies published in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology.20 Fourth, the availability of this multiserotype ELISA offers the future possibility of widespread and rapid screening for cardiovascularly significant periodontal disease, even outside dental practices. One limitation—because of the observational nature of this study, its results may still have been confounded by unrecognized associations with other risk factors for atherosclerosis.Proof that periodontal disease can directly cause atherosclerosis requires experimental intervention either to stimulate periodontal disease or reverse it. Intravenous administration of P. gingivalis has been shown to potentiate atherosclerosis in a murine model, but this route of administration does not reflect the normal pathophysiology of periodontal disease.23 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Lalla and colleagues20 describe an elegant model of periodontal disease that uses repeated oral inoculations with P. gingivalis to produce severe periodontitis with alveolar bone loss in apoE-null mice. Importantly, experimental induction of periodontitis exacerbated early atherosclerotic lesions (fatty streaks) within 4 months. In addition, serum Il-6, aortic VCAM-1, and tissue factor antigen levels were increased in mice with P. gingivalis infection. Body weight, lipids, glucose, and renal function were unaffected by periodontal disease. Intriguingly, two infected mice (of 9) had evidence of DNA for P. gingivalis within aortic tissue. These studies provide experimental proof that periodontal disease can induce atherosclerosis, and they suggest that interventional randomized clinical trials to test the effect of periodontal treatment on atherosclerotic events are warranted.The vascular mechanism(s) by which periodontal infection could predispose to atherosclerosis remains unclear. However, there is evidence that P. gingivalis can adhere to and infect cultures of coronary endothelial cells,24 with subsequent activation and expression of cell adhesion molecules.25 Endothelial involvement is supported by the report last month from Amar et al19 in Arteriosclerosis, Thrombosis, and Vascular Biology that relatively young patients with severe periodontal disease exhibit perturbed flow-mediated dilatation of the brachial artery compared with carefully matched controls. This appeared to be due to endothelial dysfunction, because nitroglycerin-mediated dilatation was normal. In line with epidemiological data, only severe periodontal disease was associated with endothelial dysfunction, and C-reactive protein was also increased in these patients. The authors made strenuous efforts to control for other risk factors for atherosclerosis, excluding patients with existing atherosclerosis, cigarette smokers, and those who have diabetes mellitus, hyperlipidemia, hypertension, and other systemic illnesses. One risk factor for both periodontal disease and atherosclerosis that they do not report is obesity; it would be interesting to know the body mass index of patients with periodontal disease and controls. Given that endothelial dysfunction appears to be an early event in the development of atherosclerosis,26 and also predicts plaque instability,27 these findings strengthen the link between periodontal disease and atherosclerosis.These important studies shed new light on the role of periodontal disease in causation of atherosclerotic events. They do not prove that treatment of periodontal disease will prevent atherosclerotic events. This is not a minor issue. For example, though it is clear that menopause substantially increases risk of atherosclerotic events in women, hormone replacement therapy (as currently used) does not appear to reduce cardiovascular events. Thus, it is now critical to test the hypothesis that reversal of periodontal disease prevents atherosclerotic events and explore different therapeutic approaches to achieve this aim. Indeed, current studies do not provide sufficient information to differentiate between the possibilities of direct infection of the vascular wall versus stimulation of a pro-inflammatory state by periodontitis.This distinction is crucial because some treatment strategies for periodontal disease, such as scaling/root planning, may promote hematogenous seeding of bacteria.28 There is evidence that brief periods of systemic or local antibiotic coverage can improve periodontal disease in conjunction with mechanical approaches.29 Other strategies, such as vaccination against P. gingivalis, may lead to a more robust immune response against shared antigens, which could have harmful vascular effects. However, there are promising data that interference with host inflammatory responses can improve periodontal disease, for example using sub-antibiotic doses of doxycycline (20 mg twice a day) to inhibit matrix metalloproteinases.30–32 These issues are particularly topical given the welcome news that the National Institutes of Health has agreed to support a randomized clinical trial of periodontal treatment in several thousand patients with both atherosclerotic and periodontal disease (PAVE trial; http://www. cscc.unc.edu/pave). Antibiotic and anti-inflammatory strategies could be incorporated in this trial, perhaps using a factorial design. The results from the PAVE trial could provide important support for the concept that infection predisposes to atherosclerosis and initiate a new clinical approach to prevention of cardiovascular events.FootnotesCorrespondence to William G. Haynes, MBChB, MD, Department of Internal Medicine (E426 GH), Carver College of Medicine, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242. E-mail [email protected] References 1 American Academy of Periodontology. Epidemiology of periodontal diseases. J Periodontol. 1996; 67: 935–945.MedlineGoogle Scholar2 Al-Zahrani MS, Bissada NF, Borawski EA. Obesity and periodontal disease in young, middle-aged, and older adults. J Periodontol. 2003; 74: 610–615.CrossrefMedlineGoogle Scholar3 Syrjanen J, Peltola J, Valtonen V, Livanainen M, et al. Dental infection associated with cerebral infarction in young and middle aged men. J Intern Med. 1989; 225: 179–184.CrossrefMedlineGoogle Scholar4 Mattila KJ, Nieminen M, Valtonen V. Association between dental health and acute myocardial infarction. BMJ. 1989; 298: 779–782.CrossrefMedlineGoogle Scholar5 Grau AJ, Buggle F, Ziegler C, Schwarz W. Association between acute cerebrovascular ischemia and chronic recurrent infection. Stroke. 1997; 28: 1724–1729.CrossrefMedlineGoogle Scholar6 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.CrossrefMedlineGoogle Scholar7 Armitage GC. Periodontal infections and cardiovascular disease: how strong is the association? Oral Dis. 2000; 6: 335–350.MedlineGoogle Scholar8 DeStefano F, Anda RF, Kahn HS, Williamson DR, Russell CM. Dental disease and risk of coronary heart disease and mortality. BMJ. 1993; 306: 688–691.CrossrefMedlineGoogle Scholar9 Beck J, Garcia R, Heiss G, Vokonas PS, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol. 1996; 67 (Suppl): 1123–1137.CrossrefGoogle Scholar10 Morrison HI, Ellison LF, Taylor GW. Periodontal disease and risk of fatal coronary heart and cerebrovascular diseases. J Cardiovasc Risk. 1999; 6: 7–11.CrossrefMedlineGoogle Scholar11 Wu T, Trevisan M, Genco RJ, Dorn JP, Falkner KL, Sempos CT. Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study. Arch Int Med. 2000; 160: 2749–2755.CrossrefMedlineGoogle Scholar12 Joshipura KJ, Rimm EB, Douglass CW, Trichopoulos D, Ascherio A, Willett WC. Poor oral health and coronary heart disease. J Dent Res. 1996; 75: 1631–1636.CrossrefMedlineGoogle Scholar13 Hujoel PP, Drangsholt M, Spiekerman C, DeRouen TA. Periodontal disease and coronary heart disease risk. JAMA. 2000; 284: 1406–1410.CrossrefMedlineGoogle Scholar14 Wu T, Trevisan M, Genco RJ, Falkner KL, Dorn JP, Sempos CT. An examination of the relation between periodontal health status and cardiovascular risk factors: serum total and HDL cholesterol, C-reactive protein, and plasma fibrinogen. Am J Epidemiol. 2000; 151: 273–282.CrossrefMedlineGoogle Scholar15 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.CrossrefMedlineGoogle Scholar16 Wick G, Schett G, Amberger A, Kleindienst R, Xu Q. Is atherosclerosis an immunologically mediated disease? Immunol Today. 1995; 16: 27–33.CrossrefMedlineGoogle Scholar17 Chiu B. Multiple infections in carotid atherosclerotic plaques. Am Heart J. 1999; 138: S534–S536.CrossrefMedlineGoogle Scholar18 Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification of periodontal pathogens in atheromatous plaques. J Periodontol. 2000; 71: 1554–1560.CrossrefMedlineGoogle Scholar19 Amar, S, Gokce N, Morgan S, Loukideli M, Van Dyke TE, Vita JA. Periodontal disease is associated with endothelial dysfunction and systemic inflammation. Arterioscler Thromb Vasc Biol. 2003; 23: 1245–1249.LinkGoogle Scholar20 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.LinkGoogle Scholar21 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; 24: 1250–1254.Google Scholar22 Genco RJ, Wu TJ, Grossi SG, Falkner K, Zambon JJ, Trevisan M. Periodontal microflora related to the risk for myocardial infarction: a case control study. J Dent Res. 1999; 78: 457. Abstract.Google Scholar23 Li L, Massas E, Batisita EL, 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.CrossrefMedlineGoogle Scholar24 Deshpande RG, Khan MB, Genco CA. Invasion of aortic and heart endothelial cells by Porphyromonas gingivalis. Infect Immun. 1998; 66: 5337–5343.CrossrefMedlineGoogle Scholar25 Khlgatian M, Nassar H, Chou HH, Gibson FC, Genco CA. Fimbria-dependent activation of cell adhesion molecule expression in Porphyromonas gingivalis-infected endothelial cells. Infect Immun. 2002; 70: 257–267.CrossrefMedlineGoogle Scholar26 Lopez JAG, Armstrong ML, Piegors DJ, Heistad DD. Effect of early and advanced atherosclerosis on vascular responses to serotonin, thromboxane A2 and ADP. Circulation. 1989; 79: 698–705.CrossrefMedlineGoogle Scholar27 Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000; 101: 948–954.CrossrefMedlineGoogle Scholar28 Lofthus JE, Waki MY, Jolkovsky DL, Otomo-Corgel J, Newman MG, Flemmig T, Nachnani S. Bacteremia following subgingival irrigation and scaling and root planing. J Periodontol. 1991; 62: 602–607.CrossrefMedlineGoogle Scholar29 American Academy of Periodontology. Systemic antibiotics in periodontics. J Periodontol. 1996; 67: 831–838.MedlineGoogle Scholar30 Golub L, Lee H, Greenwald R, et al. A matrix metalloproteinases inhibitor reduces bone-type collagen degradation fragments and bone-type collagenase in gingival crevicular fluid during adult periodontitis. Inflamm Res. 1997; 4: 310–319.Google Scholar31 Ciancio S, Ashley R. Safety and efficacy of sub-antimicrobial dose doxycycline therapy in patients with adult periodontitis. Adv Dent Res. 1998; 12: 27–31.CrossrefMedlineGoogle Scholar32 Caton J, Ciancio SG, Bleiden TM, Bradshaw M, Crout RJ, Hefti AF, Massaro JM, Polson AM, Thomas J, Walker C. Treatment with sub-antimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. J Periodontol. 2000; 71: 521–532.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Deraz O, Rangé H, Boutouyrie P, Chatzopoulou E, Asselin A, Guibout C, Van Sloten T, Bougouin W, Andrieu M, Vedié B, Thomas F, Danchin N, Jouven X, Bouchard P and Empana J (2021) Oral Condition and Incident Coronary Heart Disease: A Clustering Analysis, Journal of Dental Research, 10.1177/00220345211052507, 101:5, (526-533), Online publication date: 1-May-2022. Hodovana O, Skybchyk O, Solomenchuk T and Rumynska T (2021) ASSESSMENT OF THE MICROBIAL CONTENT OF PERIODONTAL POCKETS IN PATIENTS WITH CHRONIC GENERALIZED PERIODONTITIS AND CORONARY ARTERY DISEASE, Wiadomości Lekarskie, 10.36740/WLek202110112, 74:10, (2428-2432), Online publication date: 1-Oct-2021. Guo J, Li D, Tao H, Li G, Liu R, Dou Y, Jin T, Li L, Huang J, Hu H and Zhang J (2019) Cyclodextrin‐Derived Intrinsically Bioactive Nanoparticles for Treatment of Acute and Chronic Inflammatory Diseases, Advanced Materials, 10.1002/adma.201904607, 31:46, (1904607), Online publication date: 1-Nov-2019. Pietropaoli D, Del Pinto R, Ferri C, Ortu E and Monaco A (2019) Definition of hypertension‐associated oral pathogens in NHANES, Journal of Periodontology, 10.1002/JPER.19-0046, 90:8, (866-876), Online publication date: 1-Aug-2019. Khumaedi A, Purnamasari D, Wijaya I and Soeroso Y (2019) The relationship of diabetes, periodontitis and cardiovascular disease, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 10.1016/j.dsx.2019.03.023, 13:2, (1675-1678), Online publication date: 1-Mar-2019. Jayaprakash K, Demirel I, Khalaf H and Bengtsson T (2018) Porphyromonas gingivalis -induced inflammatory responses in THP1 cells are altered by native and modified low-density lipoproteins in a strain-dependent manner , APMIS, 10.1111/apm.12860, 126:8, (667-677), Online publication date: 1-Aug-2018. Höfer K, Noack M and Rott T (2018) Zahnmedizinische Aspekte bei der Betreuung des systemisch erkrankten Kindes, Der Freie Zahnarzt, 10.1007/s12614-017-6777-5, 62:3, (80-89), Online publication date: 1-Mar-2018. Makkar H, Reynolds M, Wadhawan A, Dagdag A, Merchant A and Postolache T (2018) Periodontal, metabolic, and cardiovascular disease: Exploring the role of inflammation and mental health, Pteridines, 10.1515/pteridines-2018-0013, 29:1, (124-163), Online publication date: 1-Nov-2018., Online publication date: 1-Nov-2018. Park S, An S, Han W and Park J (2017) Three-dimensional measurement of periodontal surface area for quantifying inflammatory burden, Journal of Periodontal & Implant Science, 10.5051/jpis.2017.47.3.154, 47:3, (154), . Muñoz-Torres F, Mukamal K, Pai J, Willett W and Joshipura K (2017) Relationship between tooth loss and peripheral arterial disease among women, Journal of Clinical Periodontology, 10.1111/jcpe.12787, 44:10, (989-995), Online publication date: 1-Oct-2017. Ardila C and Guzmán I (2015) High levels of Porphyromonas gingivalis -induced immunoglobulin G2 are associated with lower high-density lipoprotein levels in chronic periodontitis , Journal of Investigative and Clinical Dentistry, 10.1111/jicd.12169, 7:4, (368-375), Online publication date: 1-Nov-2016. Ahn Y, Shin M, Han D, Sukhbaatar M, Kim M, Shin H and Kim H (2016) Periodontitis is associated with the risk of subclinical atherosclerosis and peripheral arterial disease in Korean adults, Atherosclerosis, 10.1016/j.atherosclerosis.2016.07.898, 251, (311-318), Online publication date: 1-Aug-2016. Bartova J, Sommerova P, Lyuya-Mi Y, Mysak J, Prochazkova J, Duskova J, Janatova T and Podzimek S (2014) Periodontitis as a Risk Factor of Atherosclerosis, Journal of Immunology Research, 10.1155/2014/636893, 2014, (1-9), . Costa T, Neto J, de Oliveira A, Maia M and de Almeida A (2014) Association between Chronic Apical Periodontitis and Coronary Artery Disease, Journal of Endodontics, 10.1016/j.joen.2013.10.026, 40:2, (164-167), Online publication date: 1-Feb-2014. Rosado A, Marcos H and Gómez P (2013) Scientific evidence for the relationship between periodontitis and cardiovascular disease, World Journal of Cardiovascular Diseases, 10.4236/wjcd.2013.34A009, 03:04, (62-68), . Sheu J and Lin H (2013) Association between multiple sclerosis and chronic periodontitis: a population-based pilot study, European Journal of Neurology, 10.1111/ene.12103, 20:7, (1053-1059), Online publication date: 1-Jul-2013. Yang J, Feng L, Ren J, Wu G, Chen S, Zhou Q, Du Z, Zhang S, Hu C, Wu X and Ling L (2013) Correlation between the severity of periodontitis and coronary artery stenosis in a Chinese population, Australian Dental Journal, 10.1111/adj.12087, 58:3, (333-338), Online publication date: 1-Sep-2013. Sfyroeras G, Roussas N, Saleptsis V, Argyriou C and Giannoukas A (2012) Association between periodontal disease and stroke, Journal of Vascular Surgery, 10.1016/j.jvs.2011.10.008, 55:4, (1178-1184), Online publication date: 1-Apr-2012. Fentoğlu Ö, Köroğlu B, Kara Y, Doğan B, Yılmaz G, Sütçü R, Ay Z, Tonguç M, Orhan H, Tamer M and Kırzıoğlu F (2011) Serum Lipoprotein-Associated Phospholipase A 2 and C-Reactive Protein Levels in Association With Periodontal Disease and Hyperlipidemia , Journal of Periodontology, 10.1902/jop.2010.100417, 82:3, (350-359), Online publication date: 1-Mar-2011. Gunupati S, Chava V and Krishna B (2011) Effect of Phase I Periodontal Therapy on Anti-Cardiolipin Antibodies in Patients With Acute Myocardial Infarction Associated With Chronic Periodontitis, Journal of Periodontology, 10.1902/jop.2011.110002, 82:12, (1657-1664), Online publication date: 1-Dec-2011. Radolf J, Pillay A and Cox D (2011) Treponema and Brachyspira , Human Host-Associated Spirochetes Manual of Clinical Microbiology, 10.1128/9781555816728.ch57, (941-963), Online publication date: 16-May-2011. Pradeep A, Hadge P, Arjun Raju P, Shetty S, Shareef K and Guruprasad C (2010) Periodontitis as a risk factor for cerebrovascular accident: a case-control study in the Indian population, Journal of Periodontal Research, 10.1111/j.1600-0765.2009.01220.x, 45:2, (223-228), Online publication date: 1-Apr-2010. Griffiths R and Barbour S (2017) Lipoproteins and lipoprotein metabolism in periodontal disease, Clinical Lipidology, 10.2217/clp.10.27, 5:3, (397-411), Online publication date: 1-Jun-2010. Kshirsagar A, Craig R, Moss K, Beck J, Offenbacher S, Kotanko P, Klemmer P, Yoshino M, Levin N, Yip J, Almas K, Lupovici E, Usvyat L and Falk R (2009) Periodontal disease adversely affects the survival of patients with end-stage renal disease, Kidney International, 10.1038/ki.2008.660, 75:7, (746-751), Online publication date: 1-Apr-2009. Khocht A, Schleifer S, Janal M and Keller S (2009) Dental care and oral disease in alcohol-dependent persons, Journal of Substance Abuse Treatment, 10.1016/j.jsat.2008.11.009, 37:2, (214-218), Online publication date: 1-Sep-2009. Varki N, Anderson D, Herndon J, Pham T, Gregg C, Cheriyan M, Murphy J, Strobert E, Fritz J, Else J and Varki A (2009) ORIGINAL ARTICLE: Heart disease is common in humans and chimpanzees, but is caused by different pathological processes, Evolutionary Applications, 10.1111/j.1752-4571.2008.00064.x, 2:1, (101-112), Online publication date: 1-Feb-2009. Kubota T, Inoue Y, Iwai T, Kurihara N, Huang Y and Umeda M (2008) Arterial Thrombosis after Intravenous Infusion of Oral Bacterium in a Rat Model, Annals of Vascular Surgery, 10.1016/j.avsg.2008.01.005, 22:3, (412-416), Online publication date: 1-May-2008. Paraskevas S, Huizinga J and Loos B (2008) A systematic review and meta-analyses on C-reactive protein in relation to periodontitis, Journal of Clinical Periodontology, 10.1111/j.1600-051X.2007.01173.x, 35:4, (277-290), Online publication date: 1-Apr-2008. Lu H, Yeh K, Wu M, Li C and Tseng C (2008) An acute injection of Porphyromonas gingivalis lipopolysaccharide modulates the OPG/RANKL system and interleukin-6 in an ovariectomized mouse model, Oral Microbiology and Immunology, 10.1111/j.1399-302X.2007.00415.x, 23:3, (220-225), Online publication date: 1-Jun-2008. Kubota T, Inoue Y, Iwai T, Kurihara N, Huang Y and Umeda M (2008) Thrombose artérielle après perfusion intraveineuse de bactéries buccales dans un modèle chez le rat, Annales de Chirurgie Vasculaire, 10.1016/j.acvfr.2008.07.013, 22:3, (446-451), Online publication date: 1-May-2008. Kubota T, Inoue Y, Iwai T, Kurihara N, Huang Y and Umeda M (2008) Trombosis arterial tras la infusión intravenosa de bacterias orales en un modelo murino, Anales de Cirugía Vascular, 10.1016/j.acvsp.2008.07.022, 22:3, (450-455), Online publication date: 1-May-2008. Ford P, Gemmell E, Timms P, Chan A, Preston F and Seymour G (2016) Anti- P. gingivalis Response Correlates with Atherosclerosis , Journal of Dental Research, 10.1177/154405910708600105, 86:1, (35-40), Online publication date: 1-Jan-2007. Cengiz M, Bal S, Gökçay S and Cengiz K (2007) Does Periodontal Disease Reflect Atherosclerosis in Continuous Ambulatory Peritoneal Dialysis Patients?, Journal of Periodontology, 10.1902/jop.2007.060499, 78:10, (1926-1934), Online publication date: 1-Oct-2007. Yamazaki K, Honda T, Domon H, Okui T, Kajita K, Amanuma R, Kudoh C, Takashiba S, Kokeguchi S, Nishimura F, Kodama M, Aizawa Y and Oda H (2007) Relationship of periodontal infection to serum antibody levels to periodontopathic bacteria and inflammatory markers in periodontitis patients with coronary heart disease, Clinical and Experimental Immunology, 10.1111/j.1365-2249.2007.03450.x, 149:3, (445-452), Online publication date: 23-Jul-2007. Paquette D, Brodala N and Nichols T (2007) Cardiovascular disease, inflammation, and periodontal infection, Periodontology 2000, 10.1111/j.1600-0757.2006.00196.x, 44:1, (113-126), Online publication date: 1-Jun-2007. Gotsman I, Lotan C, Soskolne W, Rassovsky S, Pugatsch T, Lapidus L, Novikov Y, Masrawa S and Stabholz A (2007) Periodontal Destruction Is Associated With Coronary Artery Disease and Periodontal Infection With Acute Coronary Syndrome, Journal of Periodontology, 10.1902/jop.2007.060301, 78:5, (849-858), Online publication date: 1-May-2007. Schillinger T, Kluger W, Exner M, Mlekusch W, Sabeti S, Amighi J, Wagner O, Minar E and Schillinger M (2006) Dental and Periodontal Status and Risk for Progression of Carotid Atherosclerosis, Stroke, 37:9, (2271-2276), Online publication date: 1-Sep-2006. Senpuku H, Tada A, Uehara S, Kariyama R and Kumon H (2016) Post-operative Infection by Pathogenic Micro-organisms in the Oral Cavity of Patients with Prostatic Carcinoma, Journal of International Medical Research, 10.1177/147323000603400112, 34:1, (95-102), Online publication date: 1-Jan-2006. Padilla C, Lobos O, Hubert E, Gonzalez C, Matus S, Pereira M, Hasbun S and Descouvieres C (2006) Periodontal pathogens in atheromatous plaques isolated from patients with chronic periodontitis, Journal of Periodontal Research, 10.1111/j.1600-0765.2006.00882.x, 41:4, (350-353), Online publication date: 1-Aug-2006. Chen L, Chiang C, Chan C, Hung K and Huang C (2006) Does Periodontitis Reflect Inflammation and Malnutrition Status in Hemodialysis Patients?, American Journal of Kidney Diseases, 10.1053/j.ajkd.2006.01.018, 47:5, (815-822), Online publication date: 1-May-2006. Zheng P, Chen H, Shi S, Jepsen S and Eberhard J (2006) Periodontal parameters and platelet-activating factor levels in serum and gingival crevicular fluid in a Chinese population, Journal of Clinical Periodontology, 10.1111/j.1600-051X.2006.00987.x, 33:11, (797-802), Online publication date: 1-Nov-2006. Brodala N, Merricks E, Bellinger D, Damrongsri D, Offenbacher S, Beck J, Madianos P, Sotres D, Chang Y, Koch G and Nichols T (2005) Porphyromonas gingivalis Bacteremia Induces Coronary and Aortic Atherosclerosis in Normocholesterolemic and Hypercholesterolemic Pigs, Arteriosclerosis, Thrombosis, and Vascular Biology, 25:7, (1446-1451), Online publication date: 1-Jul-2005. Mattila K, Pussinen P and Paju S (2005) Dental Infections and Cardiovascular Diseases: A Review, Journal of Periodontology, 10.1902/jop.2005.76.11-S.2085, 76:11-s, (2085-2088), Online publication date: 1-Nov-2005. Cullen P, Rauterberg J and Lorkowski S (2005) The Pathogenesis of Atherosclerosis Atherosclerosis: Diet and Drugs, 10.1007/3-540-27661-0_1, (3-70), . Phillips M, Cataneo R, Greenberg J, Munawar M, Nachnani S and Samtani S (2005) Pilot study of a breath test for volatile organic compounds associated with oral malodor: evidence for the role of oxidative stress, Oral Diseases, 10.1111/j.1601-0825.2005.01085.x, 11:s1, (32-34), Online publication date: 1-Mar-2005. Fiehn N, Larsen T, Christiansen N, Holmstrup P and Schroeder T (2005) Identification of Periodontal Pathogens in Atherosclerotic Vessels, Journal of Periodontology, 10.1902/jop.2005.76.5.731, 76:5, (731-736), Online publication date: 1-May-2005. Loos B (2005) Systemic Markers of Inflammation in Periodontitis, Journal of Periodontology, 10.1902/jop.2005.76.11-S.2106, 76:11-s, (2106-2115), Online publication date: 1-Nov-2005. Kierek‐Pearson K and Karatan E (2005) Biofilm Development in Bacteria Advances in Applied Microbiology Volume 57, 10.1016/S0065-2164(05)57003-5, (79-111), . Kshirsagar A, Moss K, Elter J, Beck J, Offenbacher S and Falk R (2005) Periodontal disease is associated with renal insufficiency in the Atherosclerosis Risk In Communities (ARIC) study, American Journal of Kidney Diseases, 10.1053/j.ajkd.2004.12.009, 45:4, (650-657), Online publication date: 1-Apr-2005. Tous M, Ribas V, Ferré N, Escolà-Gil J, Blanco-Vaca F, Alonso-Villaverde C, Coll B, Camps J and Joven J (2005) Turpentine-induced inflammation reduces the hepatic expression of the multiple drug resistance gene, the plasma cholesterol concentration and the development of atherosclerosis in apolipoprotein E deficient mice, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 10.1016/j.bbalip.2005.01.003, 1733:2-3, (192-198), Online publication date: 1-Apr-2005. August 2003Vol 23, Issue 8 Advertisement Article InformationMetrics https://doi.org/10.1161/01.ATV.0000087144.24654.71PMID: 12909566 Originally publishedAugust 1, 2003 PDF download Advertisement
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