Periodontal Disease and Coronary Heart Disease
A Reappraisal of the Exposure
James D. Beck, PhD; Paul Eke, PhD, MPH, PhD; Gerardo Heiss, MD, MPH, PhD;
Phoebus Madianos, DDS, PhD; David Couper, PhD; Dongming Lin, MS; Kevin Moss, AS;
John Elter, DMD, PhD; Steven Offenbacher, DDS, PhD, MMSc
Background—Results from studies relating periodontal disease to cardiovascular disease have been mixed. Residual
confounding by smoking and use of clinical measures of periodontal disease rather than measures of infection have been
2 major criticisms. The aims of this study were to investigate relationships between prevalent coronary heart disease
(CHD) and 2 exposures, (1) clinical periodontal disease and (2) IgG antibodies to 17 oral organisms, and to evaluate
the role of smoking in these relationships.
Methods and Results—Our study is based on a subset of participants in the Atherosclerosis Risk in Communities (ARIC)
Study, who received a complete periodontal examination during visit 4 (1996–1998). The exposures were periodontal
status and serum IgG antibody levels against 17 periodontal organisms, and the outcome was prevalent CHD at visit 4.
Multivariable analyses indicate that periodontal status is not significantly associated with CHD in either ever smokers
or never smokers. Similar analyses evaluating antibodies indicate that high antibodies (above the median) to Treponema
denticola (odds ratio [OR]?1.7; 95% CI, 1.2 to 2.3), Prevotella intermedia (OR?1.5; 95% CI, 1.1 to 2.0),
Capnocytophaga ochracea (OR?1.5; 95% CI, 1.1 to 2.1), and Veillonella parvula (OR?1.7; 95% CI, 1.2 to 2.3) are
significantly associated with CHD among ever smokers, whereas Prevotella nigrescens (OR?1.7; 95% CI, 1.1 to 2.6),
Actinobacillus actinomycetemcomitans (OR?1.7; 95% CI, 1.2 to 2.7), and Capnocytophaga ochracea (OR?2.0; 95%
CI, 1.3 to 3.0) were associated with CHD among never smokers.
Conclusions—Clinical signs of periodontal disease were not associated with CHD, whereas systemic antibody response
was associated with CHD in ever smokers and never smokers. These findings indicate that the quality and quantity of
the host response to oral bacteria may be an exposure more relevant to systemic atherothrombotic coronary events than
clinical measures. (Circulation. 2005;112:19-24.)
Key Words: antibodies ? coronary disease ? epidemiology ? risk factors ? smoking
nism has been proposed whereby the burden of bacterial
pathogens, antigens, endotoxins, and inflammatory cytokines
of periodontitis contributes to the process of atherogenesis
and thromboembolic events. In response to infection and
inflammation, susceptible individuals may exhibit greater
expression of local and systemic mediators and may thereby
be at increased risk for a myocardial infarction or stroke.2
Case-control, cross-sectional, and longitudinal studies have
found that periodontitis is associated with coronary heart
disease (CHD) and cerebrovascular disease, even after adjust-
ment for a variety of potential confounders of these associa-
tions.3–26However, other studies have found either nonsig-
nificant positive trends or no association after adjustment for
variables considered to be confounders.27–31
eriodontitis is a chronic infection by oral bacteria that
affects the supporting structures of the teeth.1A mecha-
Concerns about the validity of the periodontitis–cardiovas-
cular disease associations have been expressed. A review by
Danesh32noted that studies were based on clinical measures
of periodontal disease and did not have direct measures of the
infection, such as bacterial counts or systemic antibody levels
to oral pathogens.
A second criticism focuses on the role of smoking, which
is a risk factor for both periodontal disease and heart disease
and must be considered as a confounder.33Most studies have
adjusted for smoking by means of multivariable analyses, an
approach open to bias due to residual confounding. As for
other morbidities, it has been suggested that statistical adjust-
ment is insufficient to control for smoking and that stratifi-
cation is needed.33In the present study we examined the
relationship between 2 types of periodontitis measures (clin-
ical and antibody) and prevalent CHD after stratification by
Received November 15, 2004; revision received February 24, 2005; accepted March 28, 2005.
From the Departments of Dental Ecology (J.D.B., K.M., J.E.), Epidemiology (G.H.), Biostatistics (D.C.), and Periodontology (D.L., S.O.), University
of North Carolina, Chapel Hill; Centers for Disease Control and Prevention, Division of Oral Health, Atlanta, Ga (P.E.); and University of Athens, Athens,
The online-only Data Supplement can be found with this article at http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.104.511998/DC1.
Correspondence to James D. Beck, PhD, Department of Dental Ecology, CB 7450, University of North Carolina, Chapel Hill, NC 27599. E-mail
© 2005 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.orgDOI: 10.1161/CIRCULATIONAHA.104.511998
Coronary Heart Disease
14. Emingil G, Buduneli E, Aliyev A, Akilli A, Atilla G. Association between
periodontal disease and acute myocardial infarction. J Periodontol. 2000;
15. Desvarieux M, Demmer R, Rundek T, Boden-Albala B, Jacobs D Jr,
Papapanou PN, Sacco R. Relationship between periodontal disease, tooth
loss, and carotid artery plaque: the Oral Infections and Vascular Disease
Epidemiology Study (INVEST). Stroke. 2003;34:2120–2125.
16. Pussinen P, Jousilahti P, Alfthan G, Palosuo T, Asikainen S, Salomaa V.
Antibodies to periodontal pathogens are associated with coronary heart
disease. Arterioscler Throm Vasc Biol. 2003;23:1250–1254.
17. Joshipura K, Hung H, Rimm EB, Willett WC, Ascherio A. Periodontal
disease, tooth loss, and incidence of ischemic stroke. Stroke. 2003;34:
18. Amar S, Gokce N, Morgan S, Loukideli M, Van Dyke T, Vita J. Peri-
odontal disease is associated with brachial artery endothelial dysfunction
and systemic inflammation. Arterioscler Throm Vasc Biol. 2003;23:
19. DeStefano F, Anda RF, Kahn HS, Williamson DF, Russell CM. Dental
disease and risk of coronary heart disease and mortality. BMJ. 1993;306:
20. Hung H, Willett WC, Merchant A, Rosner B, Ascherio A, Joshipura K.
Oral health and peripheral arterial disease. Circulation. 2002;107:
21. Mattila KJ, Valtonen VV, Nieminen M, Huttunen JK. Dental infection
and the risk of new coronary events: prospective study of patients with
documented coronary artery disease. Clin Infect Dis. 1995;20:588–592.
22. Mendez MV, Scott T, LaMorte W, Vokonas P, Menzoian JO, Garcia R.
An association between periodontal disease and peripheral vascular
disease. Am J Surg. 1998;176:153–157.
23. Morrison H, Ellison L, Taylor G. Periodontal disease and risk of fatal
coronary heart and cerebrovascular disease. J Cardiovasc Risk. 1999;
24. Jansson L, Lavstedt S, Frithiof L, Theobald H. Relationship between oral
health and mortality in cardiovascular diseases. J Clin Periodontol. 2001;
25. Ajawani S, Mattila K, Narhi T, Tilvis R, Ainamo A. Oral health status,
C-reactive protein and mortality: a ten year follow-up study. Gerodon-
26. Elter JR, Offenbacher S, Toole JF, Beck JD. Relationship of periodontal
disease and edentulism to stroke/TIA. J Dent Res. 2003;82:998–1001.
27. Joshipura KJ, Rimm EB, Douglass CW, Trichopoulos D, Ascherio A,
Willett WC. Poor oral health and coronary heart disease. J Dent Res.
28. Howell TH, Ridker PM, Ajani UA, Hennekens CH, Christen WG. Peri-
odontal disease and risk of subsequent cardiovascular disease in U.S.
male physicians. J Am Coll Cardiol. 2001;37:445–450.
29. Hujoel P, Drangsholt M, Spiekerman C, DeRouen T. Periodontal disease
and coronary heart disease risk. JAMA. 2000;284:1406–1410.
30. Hujoel P, Drangsholt M, Spiekerman C, DeRouen T. Examining the link
between coronary heart disease and the elimination of chronic dental
infections. J Am Dent Assoc. 2001;132:883–889.
31. Hujoel P, Drangsholt M, Spiekerman C, DeRouen T. Pre-existing car-
diovascular disease and periodontitis: a follow-up study. J Dent Res.
32. Danesh J. Coronary heart disease, Helicobacter pylori, dental disease,
Chlamydia pneumoniae, and cytomegalovirus. Am Heart J. 1999;138:
33. Hujoel P, Drangsholt M, Spiekerman C, DeRouen T. Periodontitis:
systemic disease associations in the presence of smoking: causal or
coincidental? Periodontol 2000. 2002;30:51–60.
34. Heiss G. Atherosclerosis Risk in Communities: a follow-up study of early
arterial lesions in the general population. In: Glagov S, ed. Pathology of
Human Atherosclerotic Plaque. New York, NY: Springer-Verlag; 1989:
35. The ARIC Investigators. The Atherosclerosis Risk in Communities
(ARIC) Study: design and objectives. Am J Epidemiol. 1989;129:
36. Rosamond WD, Chambless LE, Folsom AR, Cooper LS, Conwill DE,
Clegg L, Wang CH, Heiss G. Trends in the incidence of myocardial
infarction and in mortality due to coronary heart disease, 1987 to 1994.
N Engl J Med. 1998;339:861–867.
37. Sakellari D, Socransky S, Dibart S, Taubman M. Estimation of serum
antibody to subgingival species using checkerboard immunoblotting.
Oral Microbiol Immunol. 1997;12:303–310.
38. Socransky S, Haffajee A, Cugin M, Smith C, Kent R. Microbial com-
plexes in subgingival plaque. J Clin Periodontol. 1998;25:134–144.
39. Beck J, Offenbacher S. Oral health and systemic disease: periodontitis
and cardiovascular disease. J Dent Educ. 1998;62:859–870.
40. Furnival G, Wilson R. Regression by leaps and bounds. Technometrics.
41. Offenbacher S, Madianos PN, Champagne C, Southerland JH, Paquette
D, Williams R, Slade GD, Beck J. Periodontitis-atherosclerosis syn-
drome: an expanded model of pathogenesis. J Periodontal Res. 1999;34:
42. Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification
of periodontal pathogens in atheromatous plaques. J Periodontol. 2000;
43. Okuda K, Ishihara K, Nakagawa T, Hirayama A, Inayama Y. Detection
of Treponema denticola in atherosclerotic lesions. J Clin Microbiol.
44. Dorn B, Dunn WJ, Progulske-Fox A. Invasion of human coronary artery
cells by periodontal pathogens. Infect Immun. 1999;67:5792–5798.
45. 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.
46. Califano J, Schifferle R, Gunsolley J, Best A, Schenkein HA, Tew J.
Antibody reactive with Porphyromonas gingivalis serotypes K1–6 in
adults and generalized early-onset periodontitis. J Periodontol. 1999;70:
47. Papapanou PN, Neiderud A, Papadimitriou A, Sandros J, Dahlen G.
“Checkerboard” assessments of periodontal microbiota and serum
antibody responses: a case-control study. J Periodontal. 2000;71:
48. Kojima T, Yano K, Ishikawa I. Relationships between serum antibody
levels and subgingival colonization of Porphyromonas gingivalis in
patients with various types of periodontitis. J Periodontol. 1997;68:
49. Ebersole JL, Cappelli D, Stewen MJ, Willmann DE, O’Dell DS. Host
response assessment in recurring periodontitis. J Clin Periodontol. 1996;
50. Tanner AC, Kent RL Jr, Maiden MF, Macuch PJ, Taubman MA. Serum
IgG reactivity to subgingival bacteria in initial periodontitis, gingivitis
and healthy subjects. J Clin Periodontol. 2000;27:473–480.
51. Persson G, Schlegal-Bregenzer B, Chung W, Huston L, Oswald T, Robert
M. Serum antibody titers to Bacteroides forsythus in elderly subjects with
gingivitis and periodontitis. J Clin Periodontol. 2000;27:839–845.
July 5, 2005