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LE Magazine November 2004
Oral Health

Periodontal disease and cardiovascular disease: epidemiology and possible mechanisms.
BACKGROUND: Many early epidemiologic studies reported an association between periodontal disease and cardiovascular disease. However, other studies found no association or nonsignificant trends. This report summarizes the evidence from epidemiologic studies and studies that focused on potential contributing mechanisms to provide a more complete picture of the association between periodontal and heart disease. TYPES OF STUDIES REVIEWED: The authors summarize the longitudinal studies reported to date, because they represent the highest level of evidence available regarding the connection between periodontal disease and heart disease. The authors also review many of the case-control and cross-sectional studies published, as well as findings from clinical, animal, and basic laboratory studies. RESULTS: The evidence suggests a moderate association—but not a causal relationship—between periodontal disease and heart disease. Results of some case-control studies indicate that subgingival periodontal pathogenic infection may be associated with myocardial infarction. Basic laboratory studies point to the biological plausibility of this association, since oral bacteria have been found in carotid atheromas and some oral bacteria may be associated with platelet aggregation, an event important for thrombosis. Animal studies have shown that atheroma formation can be enhanced by exposure to periodontal pathogens. CONCLUSIONS: The accumulation of epidemiologic, in vitro, clinical, and animal evidence suggests that periodontal infection may be a contributing risk factor for heart disease. However, legitimate concerns have arisen about the nature of this relationship. These are early investigations. Since even a moderate risk contributed by periodontal disease to heart disease could contribute to significant morbidity and mortality, it is imperative that further studies be conducted to evaluate this relationship. One particularly important study to be carried out is the investigation of a possible clinically meaningful reduction in heart disease resulting from the prevention or treatment of periodontal disease.

J Am Dent Assoc. 2002 Jun;133 Suppl:14S-22S

Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients.

BACKGROUND: Periodontitis is a common, often undiagnosed, chronic infection of the supporting tissues of the teeth, epidemiologically associated with cardiovascular diseases. Since C-reactive protein (CRP) and other systemic markers of inflammation have been identified as risk factors for cardiovascular diseases, we investigated whether these factors were elevated in periodontitis. METHODS: Consecutive adult patients with periodontitis (localized n = 53; generalized n = 54), and healthy controls (n = 43), all without any other medical disorder, were recruited and peripheral blood samples were taken. RESULTS: Patients with generalized periodontitis and localized periodontitis had higher median CRP levels than controls (1.45 and 1.30 versus 0.90 mg/L, respectively, P = 0.030); 52% of generalized periodontitis patients and 36% of the localized periodontitis patients were sero-positive for interleukin-6 (IL-6), compared to 26% of controls (P= 0.008). Plasma IL-6 levels were higher in periodontitis patients than in controls (P = 0.015). Leukocytes were also elevated in generalized periodontitis (7.0 x 10(9)/L) compared to localized periodontitis and controls (6.0 and 5.8 x 10(9)/L, respectively, P= 0.002); this finding was primarily explained by higher numbers of neutrophils in periodontitis (P= 0.001). IL-6 and CRP correlated with each other, and both CRP and IL-6 levels correlated with neutrophils. The current findings for periodontitis were controlled for other known factors associated with cardiovascular diseases, including age, education, body mass index, smoking, hypertension, cholesterol, and sero-positivity for CMV, Chlamydia pneumoniae, and Helicobacter pylori. CONCLUSIONS: Periodontitis results in higher systemic levels of CRP, IL-6, and neutrophils. These elevated inflammatory factors may increase inflammatory activity in atherosclerotic lesions, potentially increasing the risk for cardiac or cerebrovascular events.

J Periodontol. 2000 Oct;71(10):1528-34

Potential associations between chronic respiratory disease and periodontal disease: analysis of National Health and Nutrition Examination Survey III.

BACKGROUND: Associations between poor oral health and chronic lung disease have recently been reported. The present study evaluated these potential associations by analyzing data from the National Health and Nutrition Examination Survey III (NHANES III), which documents the general health and nutritional status of randomly selected United States subjects from 1988 to 1994. METHODS: This cross-sectional, retrospective study of the NHANES III database included a study population of 13,792 subjects > or = 20 years of age with at least 6 natural teeth. A history of bronchitis and/or emphysema was recorded from the medical questionnaire, and a dichotomized variable combined those with either chronic bronchitis and/or emphysema, together considered as chronic obstructive pulmonary disease (COPD). Subject lung function was estimated by calculating the ratio of forced expiratory volume (FEV) after 1 second (FEV1)/forced vital capacity (FVC). Oral health status was assessed from the DMFS/T index (summary of cumulative caries experience), gingival bleeding, gingival recession, gingival probing depth, and periodontal attachment level. Unweighted analyses were used for initial examination of the data, and a weighted analysis was performed in a final logistic regression model adjusting for age, gender, race and ethnicity, education, income, frequency of dental visits, diabetes mellitus, smoking, and alcohol use. RESULTS: The mean age of all subjects was 44.4 +/- 17.8 years (mean +/- SD): COPD = 51.2 +/- 17.9 years and subjects without COPD = 43.9 +/- 17.7 years. Subjects with a history of COPD had more periodontal attachment loss than subjects without COPD (1.48 +/- 1.35 mm versus 1.17 +/- 1.09 mm, P = 0.0001). Subjects with mean attachment loss (MAL) > or = 3.0 mm had a higher risk of COPD than those having MAL < 3.0 mm (odds ratio, 1.45; 95% CI, 1.02 to 2.05). A trend was noted in that lung function appeared to diminish with increasing periodontal attachment loss. CONCLUSIONS: The findings of the present analysis support recently published reports that suggest an association between periodontal disease and COPD.

J Periodontol. 2001 Jan;72(1):50-6

Inter-relationships between rheumatoid arthritis and periodontal disease. A review.

This review looks at the considerable similarities between periodontal disease and rheumatoid arthritis (RA). While the etiology of these two diseases may differ, the underlying pathogenic mechanisms are remarkably similar and it is possible that individuals manifesting both periodontitis and RA may suffer from a unifying underlying systemic dysregulation of the inflammatory response. In light of these findings, the implications for the use of disease-modifying medications in the management of these two chronic inflammatory conditions is apparent. Further longitudinal studies and medication-based intervention studies are required to determine just how closely these two conditions are allied.

J Clin Periodontol. 2003 Sep;30(9):761-72

Comparison of body composition and periodontal disease using nutritional assessment techniques: Third National Health and Nutrition Examination Survey (NHANES III).

OBJECTIVES: The objective of this study was to investigate the association of body composition (obesity) and periodontal disease using simple, inexpensive nutritional assessment techniques available in the Third National Health and Nutrition Examination Survey (NHANES III). MATERIAL AND METHODS: Caucasian subjects, aged 18 years and above, participating in NHANES III, were used for this study. Weight, height, waist circumference, hip circumference, skinfold thickness (S), and bioelectrical impedance analysis measurements were performed and used in the calculation of body mass index (BMI), waist-to-hip ratio (WHR) (visceral fat), log sum of S (subcutaneous fat), and fat-free mass (FFM). Data were analyzed using SPSS. One-way, factorial ANOVA, multivariate analyses, and regression curve analyses were performed. p<0.05 was used to reject the null hypothesis. RESULTS: Adjusting for age, gender, history of diabetes, current smoking, and socioeconomic status, statistically significant correlations were found between periodontitis and WHR, BMI, FFM, and in some instances S. CONCLUSION: This study, indicating significant correlations between body composition and periodontal disease (with WHR being the most significant, followed by BMI, FFM, and S), showed similarities to those observed in other obesity-related health problems. This strengthened arguments that periodontal disease and certain obesity-related systemic illnesses are related, with abnormal fat metabolism possibly being an important factor.

J Clin Periodontol. 2003 Apr;30(4):321-7

Osteoporosis: a possible modifying factor in oral bone loss.

There has been increasing interest in the interrelationship between systemic osteoporosis, oral bone loss, tooth loss, and risk factors for these conditions. Because the severity of alveolar bone loss increases with age, it has long been hypothesized that it may, in part, be related to systemic conditions that also predispose the patient to osteoporosis/osteopenia. The purpose of this paper is to review the risk factors for osteoporosis and periodontitis, as well as the evidence that loss of oral bone mineral may be related to systemic osteopenia. There is also evidence that therapies designed to influence systemic bone mineral density, such as hormone replacement and bisphosphonate therapy, may be associated with less tooth loss and a slower loss of alveolar bone, respectively.

Ann Periodontol. 1998 Jul;3(1):312-21

Tooth loss and skeletal bone density in healthy postmenopausal women.

Associations between dental status and skeletal bone density were investigated in a group of 329 healthy postmenopausal women with normal bone density. Bone mineral density (BMD) of the lumbar spine, femoral neck and distal radius were measured by dual- or single-photon absorptiometry. Number of teeth remaining were counted and presence of complete dentures noted by a nurse practitioner. Forty-eight women (15%) wore a complete maxillary and/or mandibular denture: 22(7%) were completely edentulous and an additional 26 (8%) had one edentulous ridge. Among women without complete dentures (n = 281), significant positive linear relationships were observed between number of teeth and BMD at the spine (p < 0.05) and radius (p < 0.01), controlling for years since menopause, pack-years of smoking, education and body mass index. BMD did not differ between the groups with and without dentures. However, women who acquired dentures after the age of 40 years had significantly lower mean spinal and radial BMD than women who acquired dentures at age 40 years or earlier (at the radius, 0.584 +/- 0.015 v 0.630 +/- 0.017 g/cm2, p < 0.05; at the spine, 1.043 +/- 0.031 v 1.124 +/- 0.029 g/cm2, p = 0.05). In linear regression analysis, significant independent correlations were found among all women (n = 329) between number of teeth and age (partial r = -0.19, p < 0.001), pack-years of cigarette use (partial r = -0.23, p < 0.001) and years of education (partial r = +0.11, p < 0.05). These associations between dental status and BMD support the hypothesis that systemic bone loss may contribute to tooth loss.

Osteoporos Int. 1994 Mar;4(2):104-9

Periodontal infection and preterm birth: results of a prospective study.

BACKGROUND: Previous studies have suggested that chronic periodontal infection may be associated with preterm births. The authors conducted a prospective study to test for this association. METHODS: A total of 1,313 pregnant women were recruited from the Perinatal Emphasis Research Center at the University of Alabama at Birmingham. Complete periodontal, medical ,.and behavioral assessments were made between 21 and 24 weeks gestation. After delivery, medical records were consulted to determine each infant’s gestational age at birth. From these data, the authors calculated relationships between periodontal disease and preterm birth, while adjusting for smoking, parity (the state or fact of having born offspring), race, and maternal age. Results were expressed as odds ratios and 95% confidence intervals, or CIs. RESULTS: Patients with severe or generalized periodontal disease had adjusted odds ratios (95% CI) of 4.45 (2.16-9.18) for preterm delivery (that is, before 37 weeks gestational age). The adjusted odds ratio increased with increasing prematurity to 5.28 (2.05-13.60) before 35 weeks’ gestational age and to 7.07 (1.70-27.4) before 32 weeks’ gestational age. CONCLUSIONS: The authors’ data show an association between the presence of periodontitis at 21 to 24 weeks’ gestation and subsequent preterm birth. Further studies are needed to determine whether periodontitis is the cause. CLINICAL IMPLICATIONS: While this large prospective study has shown a significant association between preterm birth and periodontitis at 21 to 24 weeks’ gestation, neither it nor other studies to date were designed to determine whether treatment of periodontitis will reduce the risk of preterm birth. Pending an answer to this important question, it remains appropriate to advise expectant mothers about the importance of good oral health.

J Am Dent Assoc. 2001 Jul;132(7):875-80

Women’s health issues and their relationship to periodontitis.

BACKGROUND: The emergence of sex-specific associations between periodontitis and certain systemic disorders has prompted researchers to investigate the possibility of associations between periodontitis and specific women’s health issues. The authors review the potential relationships between periodontitis and hormonal changes and their ramifications in regard to pregnancy outcomes, cardiovascular disease, or CVD, and osteoporosis. METHODS: Changes in hormone levels, such as those that occur during puberty, pregnancy, menstruation and menopause, as well as those that occur with the use of hormonal supplements, have long been associated with the development of gingivitis. Furthermore, bacterial anaerobes have been found to change during the normal hormonal cycle. In periodontitis, the inflammatory response results in ulceration of the gingivae and the subsequent entry of bacterial cells, bacterial products, peptidoglycan fragments and hydrolytic enzymes into the systemic circulation. The result is a systemic response of increased cytokines and biological mediators, as well as increased levels of serum antibodies. RESULTS: Some researchers have found that pregnant women with periodontitis were 7.5 times more likely to have a preterm low-birth-weight infant than were control subjects. Other researchers reported that the risk of preterm birth was directly related to the severity of periodontitis. Similarly, researchers have linked periodontitis to CVD. Many studies have indicated that estrogen exerts a protective effect against CVD development, and much evidence suggests that when hormone replacement therapy is administered to postmenopausal women, this effect continues. A relationship between periodontitis and osteoporosis has been established, such that more clinical attachment loss has been noted in osteoporotic people. CONCLUSIONS: The literature suggests that more sex-specific research is essential to determine the strategies needed to prevent and treat adverse pregnancy outcomes, CVD and osteoporosis through hormone modification and periodontitis control. CLINICAL IMPLICATIONS: Dentists must assume greater responsibility for the overall health of their patients, and acquire knowledge of relevant systemic conditions to interact meaningfully with medical colleagues.

J Am Dent Assoc. 2002 Mar;133(3):323-9

Relationship of periodontal disease to carotid artery intima-media wall thickness: the atherosclerosis risk in communities (ARIC) study.

Periodontitis has been linked to clinical cardiovascular disease but not to subclinical atherosclerosis. The purpose of this study was to determine whether periodontitis is associated with carotid artery intima-media wall thickness (IMT). Cross-sectional data on 6,017 persons aged 52 to 75 years were obtained from the Atherosclerosis Risk in Communities Study 1996 to 1998 examination. The dependent variable was carotid IMT >/=1 mm. Periodontitis was defined by extent of attachment loss >/=3 mm: none/mild (<10%), moderate (10% to <30%), or severe (>/=30%). Covariates included age, sex, diabetes, LDL cholesterol, HDL cholesterol, triglycerides, hypertension, smoking, waist-hip ratio, education, and race/study center. Odds of IMT >/=1 mm were higher for severe periodontitis (OR 2.09, 95% CI 1.73 to 2.53) and moderate periodontitis (OR 1.40, CI 1.17 to 1.67) compared with no periodontitis. In a multivariable logistic regression model, severe periodontitis (OR 1.31, CI 1.03 to 1.66) was associated with IMT >/=1 mm, while adjusting for the other factors in the model. These results provide the first indication that periodontitis may play a role in the pathogenesis of atheroma formation, as well as in cardiovascular events.

Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1816-22

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