| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
RESEARCH REPORT |
1 Department of Dental Public Health Sciences, School of Dentistry, Box 357475,
2 Department of Epidemiology, School of Public Health,
3 Department of Oral Medicine, School of Dentistry,
4 Department of Biostatistics, School of Public Health, and
5 Department of Medicine, Cardiovascular Health Research Unit, Department of Dental Public Health Sciences, University of Washington, Seattle, WA 98195;
*corresponding author, hujoel{at}u.washington.edu
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
|---|
KEY WORDS: coronary heart disease • periodontitis • prospective cohort study • pre-existing cardiovascular disease
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
|---|
The extent to which these three assumptions hold is uncertain. The primary goal of this study is to evaluate, utilizing the NHANES I Epidemiologic Follow-up Study (NHEFS), the evidence concerning the first assumption, whether periodontitis increases the risk for coronary heart disease among individuals with pre-existing cardiovascular disease.
|
MATERIALS & METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
|---|
At-risk Individuals
The analyses were limited to those individuals with evidence of prior cardiovascular disease as determined by a ‘yes’ answer to any of the following four questions: "Has a doctor ever told you that you had a heart attack?" "Has a doctor ever told you that you had a stroke?" "Has a doctor ever told you that you have heart failure?" and, "During the past 6 months have you used any medicine, drugs, or pills for a weak heart?" A subgroup analysis was limited to those individuals with a self-reported prior heart attack.
Outcome and Exposure Definition
The baseline information included a medical examination, a standardized medical history, a standardized dental examination, laboratory tests, and a single 24-hour dietary recall. Demographic variables in the risk models included age at baseline, gender, race (Caucasian, African-American, and other), education, poverty index, and marital state (categorized as ever-married vs. never-married) of the examined person. Cardiovascular risk factors evaluated at the baseline clinical examination included systolic and diastolic blood pressure, serum cholesterol, history of diabetes, physical activity (an individual was defined as physically active if he/she reported to be either very active in his/her usual day, aside from recreation, or if he/she reported much exercise for recreation), height and weight, alcohol consumption (glasses/day), smoking duration (in yrs), the average number of cigarettes smoked a day during the smoking yrs, and a history of a nervous breakdown. For smoking, information regarding the duration of smoking and the average number of cigarettes smoked prior to the baseline examination (1971-1975) was derived from 16 questions asked during the interview in 1982-1984. Validation studies have indicated that surrogate- and self-responses on cigarette smoking obtained approximately 10 yrs after the baseline interview (1971-1975) were not remarkably different from responses obtained in the follow-up interview (1982-1984) (McLaughlin et al., 1987; Coultas et al., 1988).
A coronary heart disease event was defined as one of the following outcomes: (1) death with an underlying CHD cause of death coded 410 through 414 according to the International Classification of Disease, 9th rev. (ICD-9); (2) a hospital stay with a discharge diagnosis code 410-414 according to the ICD-9, Clinical Modification Codes; or (3) either of the following coronary revascularization procedures: 36.10-36.19 (coronary revascularization) or 36.00-36.09 (removal of coronary obstruction). The first occurrence of any of these three events (CHD fatality, hospitalization because of coronary heart disease, hospitalization because of revascularization) was used as the defining event.
Three mutually exclusive periodontal classifications were defined: (i) periodontitis (the presence of 4 or more teeth with pockets, n = 236); (ii) gingivitis (n = 186); and (iii) periodontal health, i.e., no clinical signs of periodontitis or gingivitis (n = 214). Individuals with periodontitis had periodontal pockets with attachment loss (i.e., not merely a deepened gingival crevice due to swelling in the free gingiva). Individuals with gingivitis had an overt area of inflammation which may completely circumscribe the tooth and which may have been associated with pseudo-pockets.
Statistical Methodology
We fitted Cox proportional hazard models to assess whether individuals with periodontitis or gingivitis at baseline are at higher risk for a coronary heart disease event than individuals with no signs of periodontal disease at baseline. Time-on-study was used as the time scale for all time-to-event analyses. Potentially confounding variables were included in the model by a "forward elimination" process (Maclure, 1990). With this approach, potentially confounding variables representing competing hypotheses are added to the model. Since the use of ratios such as body mass index and pack-years can induce spurious correlations (Kronmal, 1993), factors and interaction terms rather than ratios were modeled. Three different approaches for taking into account the sampling design were evaluated: (1) a model-based analysis assuming that the sample was a simple random sample; (2) a design-based analysis taking into account the stratification and clustering, but ignoring the sampling weights; and (3) a design-based analysis incorporating both the clustering, stratification, and the sampling weights (Korn and Graubard, 1991; Breslow et al., 1999; Graubard and Korn, 1999). Which analysis is appropriate is a subtle question that depends on a trade-off between efficiency and absence of bias. The primary results reported in the Tables take into account the sampling design but not the sampling weights. This approach was selected because the sampling weights are primarily determined by design variables such as age, race, poverty census enumeration district, and family income. Since these design variables were partially captured by the socio-economic variables included in the statistical models, not using the sampling weights in the analyses provides a good compromise between bias and efficiency (Breslow et al., 1999). Since the associations between periodontitis and coronary heart disease were small and sensitive to the analytic approach selected, all three approaches were presented for the key analyses within the results, so that the robustness of the conclusions could be evaluated by the reader. Analyses which adjusted for the sampling design and/or weights were performed with the use of SUDAAN software (Shah et al., 1997). Baseline differences were assessed by means of analysis of variance models for continuous variables and logistic regression models for binary variables.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
|---|
). When compared with individuals with a healthy periodontium, individuals with periodontitis and gingivitis were significantly more likely to be older, male, less educated, African-American, and poorer. Although individuals with periodontitis exercised less and had a longer smoking history, they were not significantly different (P < 0.01) from individuals with a healthy periodontium with respect to most cardiovascular risk factors.
|
). After adjustment for confounders and sampling design, the relative risk of coronary heart disease for individuals with periodontitis decreased to 0.97 (95% confidence interval, 0.72-1.31). Adjustment for the sampling weights further decreased the relative risk to 0.79 (95% confidence interval, 0.54-1.14).
|
Gingivitis and Coronary Heart Disease Risk among At-risk Individuals
Unadjusted for confounding variables, gingivitis was associated with a 17% increased risk for coronary heart disease events when compared with a healthy periodontium (Relative risk, 1.17; 95% confidence interval, 0.90 -1.53). After adjustment for potentially confounding variables and the sampling design, gingivitis was not associated with a significantly increased risk of coronary heart disease (Relative risk, 1.09; 95% confidence interval, 0.79-1.50) (Table 2
). Inclusion of the sampling weights further decreased the size of the relative risk (Relative risk, 0.76; 95% confidence interval, 0.50-1.15). There was no significant association between gingivitis and fatal coronary heart disease (Relative risk, 1.09; 95% confidence interval, 0.60-1.99).
Subgroup Analysis
When limited to only those individuals who reported having a prior heart attack, the crude hazard ratio for a coronary heart disease event associated with periodontitis was 0.97 (95% confidence interval, 0.69-1.37) (Table 3). After further adjustment for potentially confounding variables, the hazard ratio decreased to 0.66 (95% confidence interval, 0.42-1.05), suggesting that periodontitis, if it has any effect, may lower the hazard for future CHD events by 33% when compared with those individuals with healthy gums. Gingivitis was similarly not associated with an increased risk for future CHD events. The crude hazard ratio associated with gingivitis was 0.95 (95% confidence interval, 0.67-1.35), and the adjusted hazard ratio was 0.89 (95% confidence interval, 0.56-1.40). Exclusion of some of the explanatory variables with sparse data led to 5% changes in the estimates.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Suggestions have been made that significant periodontitis-CHD associations are present in subgroups of cohorts. Subgroup effects have been claimed for younger cohorts (Mattila et al., 2000), females, males (Rose et al., 2000), or individuals with pre-existing cardiovascular disease. Subgroup claims are generally unreliable (Yusuf et al., 1991). Both the lack of statistical power and the tendency for conclusions to be fitted to the data lead to a high prevalence of false-positive claims. However, since periodontal interventions have been proposed as a method of reducing CHD risk in people with pre-existing cardiovascular disease, it is important to search for supporting epidemiological evidence in such subgroups.
Currently, the NHEFS study is the only large longitudinal cohort study where individuals have had a detailed dental examination by trained examiners at the start of follow-up. In addition, with a low 4% dropout rate over an approximately 20-year follow-up, and extensive information on tobacco smoking, socio-economic factors, and demographic factors at baseline, this study provided a unique opportunity for evaluation of the associations between periodontal disease and coronary heart disease incidence in a cohort of individuals with pre-existing cardiovascular disease. The limitations of this study include its limited power, due to a relatively small number of CHD events, which did not allow for exclusion of the possibility of a small increased risk, and the possible imprecision of self-reported cardiovascular disease. In addition, since we have no data on the dental procedures that subjects underwent during follow-up, we cannot measure the influence of bacteremia caused by dental procedures on CHD risk. As well, without subsequent oral examinations, we cannot assess the potential impact of any changes in periodontal status over time.
The periodontal disease measure, the Russell Index, has recently been considered a limitation of the NHANES I study. Some investigators now believe that it is too subjective and a less accurate measure of periodontal disease than periodontal probing assessments (Genco et al., 2001). Several previous studies have shown this index to be a highly specific measure of periodontal disease, with few false-positive diagnoses, when compared with full-mouth radiographs and a full clinical examination (Russell, 1956; Sheiham and Striffler, 1970). Thus, if this measure is viewed as an indicator of moderate to severe periodontal disease, few subjects would be misclassified, compared with full-mouth radiographs with a clinical examination. It is probable that the low sensitivity of the Russell Index will lead to some non-differential misclassification in the non-periodontitis groups, but it is difficult to see how any inaccuracy in measuring this exposure, if it exists, could bias the relative risk from increased risk to the protective relationships witnessed in this study.
The consistency of these findings needs to be explored across different populations. The Physician's Health Study had over 5000 participants with prior cardiovascular disease, and any future findings in this cohort, or other cohorts, should be combined with this study to provide a more detailed picture of the potential associations between periodontitis and coronary heart disease among individuals with pre-existing coronary heart disease. Currently, we can find no evidence from this study that people with pre-existing cardiovascular disease are at an increased risk for future CHD events because of the presence of periodontitis. However, some evidence is available that dental treatments among individuals with pre-existing cardiovascular disease may precipitate coronary heart disease events. Dental procedures can be associated with bacterial endocarditis (Lacassin et al., 1995), peri-operative myocardial ischemia due to anxiety and local anesthetics (Umino and Nagao, 1993; Massalha et al., 1996; Warltier et al., 2000), and an increased chance for sepsis when preceding open-heart surgery (Hakeberg et al., 1999). Any randomized control trial results of periodontal treatments for CHD prevention should be carefully monitored for potential harms as well as benefits.
|
ACKNOWLEDGMENTS |
|---|
Received May 15, 2001; Last revision October 16, 2001; Accepted January 18, 2002
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Coultas DB, Howard CA, Peake GT, Skipper BJ, Samet JM (1988). Discrepancies between self-reported and validated cigarette smoking in a community survey of New Mexico Hispanics. Am Rev Resp Dis 137:810-814.[Medline]
Danesh J (1999). Coronary heart disease, Helicobacter pylori, dental disease, Chlamydia pneumoniae, and cytomegalovirus: meta-analyses of prospective studies. Am Heart J 138:S434-S437.[Medline]
Genco RJ, Trevisan M, Wu T, Beck JD (2001). Periodontal disease and risk of coronary heart disease. J Am Med Assoc 285:40-41.
Graubard BI, Korn EL (1999). Analyzing health surveys for cancer-related objectives. J Natl Cancer Inst 91:1005-1016.
Hakeberg M, Dernevik L, Gatzinsky P, Eklof C, Kennergren C, Jontell M (1999). The significance of oral health and dental treatment for the postoperative outcome of heart valve surgery. Scand Cardiovasc J 33:5-8.[Medline]
Hujoel PP, Drangsholt M, Spiekerman C, DeRouen TA (2000). Periodontal disease and coronary heart disease risk. J Am Med Assoc 284:1406-1410.
Joshipura K, Ritchie C, Douglass C (2000). Strength of evidence linking oral conditions and systemic disease. Compendium 21:17-28.
Korn EL, Graubard BI (1991). Epidemiologic studies utilizing surveys: accounting for the sampling design. Am J Public Health 81:1166-1173.
Kronmal RA (1993). Spurious correlation and the fallacy of the ratio standard revisited. J R Stat Soc A 156: 379-392
Lacassin F, Hoen B, Leport C, Selton-Suty C, Delahaye F, Goulet V, et al. (1995). Procedures associated with infective endocarditis in adults. A case control study [see comments]. Eur Heart J 16:1968-1974.
Maclure M (1990). Multivariate refutation of aetiological hypotheses in non-experimental epidemiology. Int J Epidemiol 19:782-787.
Massalha R, Valdman S, Farkash P, Merkin L, Herishanu Y (1996). Fatal intracerebral hemorrhage during dental treatment. Isr J Med Sci 32:774-776.[Medline]
Mattila KJ, Asikainen S, Wolf J, Jousimies-Somer H, Valtonen V, Nieminen M (2000). Age, dental infections, and coronary heart disease. J Dent Res 79:756-760.
McLaughlin JK, Dietz MS, Mehl ES, Blot WJ (1987). Reliability of surrogate information on cigarette smoking by type of information. Am J Epidemiol 126:144-146.
Rose LF, Steinberg BJ, Minsk L (2000). The relationship between periodontal disease and systemic conditions. Compendium 21:870-878.[Medline]
Russell AL (1956). A system of classification and scoring for prevalence surveys of periodontal disease. J Dent Res 35:350-359.
Shah BV, Barnwell BG, Bieler GS (1997). SUDAAN user's manual, rel. 7.5. NC: Research Triangle Institute, Research Triangle Park, NC.
Sheiham A, Striffler DF (1970). A comparison of four epidemiological methods of assessing periodontal disease. J Periodontal Res 5:155.[Medline]
Umino M, Nagao M (1993). Systemic diseases in elderly dental patients. Intl Dent J 43:213-218.
Warltier DC, Pagel PS, Kersten JR (2000). Approaches to the prevention of perioperative myocardial ischemia. Anesthesiology 92:253-259.[Medline]
Yusuf S, Wittes J, Probstfield J, Tyroler HA (1991). Analyses and interpretation of treatment effects in subgroups of patients in randomized controlled trials. J Am Med Assoc 266:93-98.[Abstract]
This article has been cited by other articles:
|
|
 |
|
  D.J. Caplan, J.B. Chasen, E.A. Krall, J. Cai, S. Kang, R.I. Garcia, S. Offenbacher, and J.D. Beck Lesions of endodontic origin and risk of coronary heart disease. J. Dent. Res., November 1, 2006; 85(11): 996 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Spahr, E. Klein, N. Khuseyinova, C. Boeckh, R. Muche, M. Kunze, D. Rothenbacher, G. Pezeshki, A. Hoffmeister, and W. Koenig 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, March 13, 2006; 166(5): 554 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Southerland, G. W. Taylor, and S. Offenbacher Diabetes and Periodontal Infection: Making the Connection Clin. Diabetes, October 1, 2005; 23(4): 171 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Beck, P. Eke, G. Heiss, P. Madianos, D. Couper, D. Lin, K. Moss, J. Elter, and S. Offenbacher Periodontal Disease and Coronary Heart Disease: A Reappraisal of the Exposure Circulation, July 5, 2005; 112(1): 19 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. L. PIHLSTROM and L. TABAK The National Institute of Dental and Craniofacial Research: Research for the practicing dentist J Am Dent Assoc, June 1, 2005; 136(6): 728 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Saremi, R. G. Nelson, M. Tulloch-Reid, R. L. Hanson, M. L. Sievers, G. W. Taylor, M. Shlossman, P. H. Bennett, R. Genco, and W. C. Knowler Periodontal Disease and Mortality in Type 2 Diabetes Diabetes Care, January 1, 2005; 28(1): 27 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Rutger Persson, O. Ohlsson, T. Pettersson, and S. Renvert Chronic periodontitis, a significant relationship with acute myocardial infarction Eur. Heart J., December 1, 2003; 24(23): 2108 - 2115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Desvarieux, R. T. Demmer, T. Rundek, B. Boden-Albala, D. R. Jacobs Jr, P. N. Papapanou, and R. L. Sacco Relationship Between Periodontal Disease, Tooth Loss, and Carotid Artery Plaque: The Oral Infections and Vascular Disease Epidemiology Study (INVEST) Stroke, September 1, 2003; 34(9): 2120 - 2125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Angeli, P. Verdecchia, C. Pellegrino, R. G. Pellegrino, G. Pellegrino, L. Prosciutti, C. Giannoni, S. Cianetti, and M. Bentivoglio Association Between Periodontal Disease and Left Ventricle Mass in Essential Hypertension Hypertension, March 1, 2003; 41(3): 488 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.P. HUJOEL Does chronic periodontitis cause coronary heart disease?: A review of the literature J Am Dent Assoc, June 1, 2002; 133(suppl_1): 31S - 36S. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| IADR Journals | Advances in Dental Research ® |
| Journal of Dental Research ® | Critical Reviews (1990-2004) |
