Periodontitis and Non-alcoholic Fatty Liver Disease, a population-based cohort investigation in the Study of Health in Pomerania.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects 20%-30% of adults with risk factors like obesity and insulin resistance putatively acting through chronic low-grade inflammation. Because periodontitis elicits low-grade inflammation, we hypothesized that it could contribute to NAFLD occurrence. OBJECTIVE: To investigate epidemiologic associations between periodontitis and the incidence of NAFLD among 2,623 participants of the Study of Health in Pomerania. METHODS: Periodontitis at baseline was defined as the percentage of sites (0%, <30%, ≥30%) with (i) clinical attachment level (CAL) ≥3 mm; (ii) probing pocket depth (PD) ≥4 mm. Incident NAFLD was defined as a significant increase in liver echogenicity on ultrasound relative to the kidneys, with the diaphragm indistinct or the echogenic walls of the portal veins invisible. RESULTS: After a median 7.7 years of follow-up, 605 incident NAFLD cases occurred at a rate of 32.5 cases per 1,000 person-years. Relative to participants without CAL ≥3 mm, NAFLD incidence was elevated slightly in participants with <30% of sites affected and moderately in participants with ≥30% of sites affected (multivariable-adjusted incidence rate ratio = 1.28, 95% CI, 0.84, 1.95 and 1.60, 95% CI, 1.05-2.43), respectively. A similar dose-response relationship was not observed for PD. CONCLUSION: History of periodontitis may be a risk factor for NAFLD.

Telomere length attrition and chronic periodontitis: an ARIC Study nested case-control study.

AIM: This nested case-control study sought to determine whether an accelerated rate of leukocyte telomere length (LTL) shortening over 6 years was associated with chronic periodontitis. MATERIALS AND METHODS: We sampled cases (n = 178) with severe chronic periodontitis and controls (n = 178) with no/mild chronic periodontitis from the Atherosclerosis Risk in Communities study. Controls were frequency-matched to cases by study site, age, sex and race. Age ranged from 53 to 73 years. Severe chronic periodontitis was defined using the CDC-AAP case classification. LTL was measured from DNA collected at two time points, 6 years apart, with quantitative polymerase chain reaction relative to a single-copy control gene. Multiple linear regression evaluated associations between LTL measured at baseline, follow-up and change scores with severe chronic periodontitis, adjusting for potential confounders. RESULTS: Cases had shorter LTL than controls at baseline (p = 0.03) and follow-up (p = 0.04) after adjusting for confounding. Overall there was a net reduction in LTL over time (p = 0.02). The rate of LTL did not differ between cases and controls (p = 0.80). CONCLUSIONS: Leukocyte telomere length shortening occurred at the same rate among adults with and without severe chronic periodontitis. This suggests that LTL shortening may have occurred earlier in the life course.

Periodontal disease measures and risk of incident peripheral artery disease: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: The association of periodontal disease with atherosclerotic cardiovascular diseases is well known, but not specifically with incident peripheral artery disease (PAD). Therefore, we studied the associations of periodontal disease with incident PAD in a population-based setting. METHODS: Among 9,793 participants (aged 53-75 years) without prevalent PAD, self-reported history of periodontal disease was ascertained. Of these, 5,872 participants underwent full-mouth examinations from which periodontal status was defined using the US Centers for Disease Control and Prevention-American Academy of Periodontology (CDC-AAP) definition. We quantified the association of periodontal disease with incident PAD (defined by hospital admission diagnosis or procedures) using multivariable Cox regression models. RESULTS: During a median follow-up of 20.1 years, 360 participants (3.6%) developed PAD. In models accounting for potential confounders including diabetes and smoking pack-years, there was higher hazard of PAD in participants with self-reported tooth loss because of periodontal disease (hazard ratio:1.54 [95% CI:1.20-1.98]), history of periodontal disease treatment (1.37 [1.05-1.80]), and periodontal disease diagnosis (1.38 [1.09-1.74]), compared to their respective counterparts. The clinical measure of periodontal disease (n = 5,872) was not significantly associated with incident PAD in the fully adjusted model (e.g., 1.53 [0.94-2.50] in CDC-AAP-defined severe periodontal disease versus no disease). CONCLUSION: We observed a modest association of self-reported periodontal disease, especially when resulting in tooth loss, with incident PAD in the general population. Nonetheless, a larger study with the clinical measure of periodontal disease is warranted.

Periodontitis and prevalence of elevated aminotransferases in the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) prevalence is greater among Hispanics/Latinos than other racial/ethnic groups and prevalence is further reported to vary among Hispanic/Latino background groups. Experimental animal and human studies demonstrate associations between periodontitis and NAFLD, not yet reported among Hispanics/Latinos. This study examined periodontitis as a novel risk factor that may contribute to the burden of NAFLD among Hispanics/Latinos. METHODS: Data came from 11,914 participants of the Hispanic Community Health Study/Study of Latinos. Periodontitis was defined as the extent (none, < 30%, ≥30%) of periodontal sites with clinical attachment level (CAL) of ≥3 mm or probing pocket depth (PD) of ≥4 mm. Elevated serum transaminases indicative of suspected NAFLD were defined as having alanine aminotransferase levels (ALT) > 40 IU/L or aspartate aminotransferase (AST) > 37 IU/L for men and ALT > 31 IU/L or AST > 31 IU/L for women. Survey-logistic regression models estimated prevalence odds ratios (POR) and 95% confidence intervals (CI) for the association between periodontitis and suspected NAFLD. RESULTS: The overall age-standardized percentage of study participants with < 30% of sites with CAL ≥3 mm or PD ≥4 mm was 53.5% and 58.6%, respectively, while participants with ≥30% sites with CAL ≥3 mm or PD ≥4 mm comprised 16% and 5.72%, respectively. The overall age-standardized prevalence (95% CI) of suspected NAFLD was 18.1% (17.1-19.0). For the entire cohort, we observed a dose-response (i.e. graded) association between PD ≥4 mm and the prevalence odds of suspected NAFLD, whereby participants with < 30% affected had a crude POR = 1.19 (95% CI: 1.03, 1.38) while participants with ≥30% affected had a crude POR = 1.39 (95% CI: 1.02, 1.90). These crude estimates were attenuated toward the null and rendered non-significant upon covariate adjustment. No differences were found by Hispanic/Latino background group. CONCLUSION: Previously reported associations between periodontitis and NAFLD were marginal to null in this study of a diverse group of Hispanics/Latinos.

Periodontal disease and coronary heart disease: a reappraisal of the exposure.

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.

Associations between IgG antibody to oral organisms and carotid intima-medial thickness in community-dwelling adults.

AIMS: The aims of this study are to describe the relationships between IgG antibodies to 17 oral organisms and atherosclerosis as indexed by carotid intima-medial wall thickness (IMT) and to evaluate the role of smoking. 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 outcome was mean carotid IMT>/=1mm assessed by B-mode ultrasound. The exposures were serum IgG antibody levels against 17 periodontal organisms using a whole bacterial checkerboard immunoblotting technique. Evaluation of all 17 antibodies indicated that antibody to Campylobacter rectus resulted in the best-fitting model (OR=2.3, 95% CI=1.83-2.84) and individuals with both high C. rectus and Peptostreptococcus micros titers had almost twice the prevalence of IMT>/=1mm than those with only a high C. rectus antibody (8.3% versus 16.3%). Stratification by smoking indicated that all microbial models significant for smokers were also significant for never smokers except for Porphyromonas gingivalis (p=0.08). CONCLUSIONS: This is the first study to report a relationship between IgG antibody reactive to oral organisms and subclinical atherosclerosis with significant relationships evident in both ever and never smokers.

Relationship between periodontal disease and C-reactive protein among adults in the Atherosclerosis Risk in Communities study.

BACKGROUND: Moderately elevated serum C-reactive protein (CRP) concentration is a systemic marker of inflammation and a documented risk factor for cardiovascular disease in otherwise healthy persons. Unrecognized infections, such as periodontal disease, may induce an acute-phase response, elevating CRP levels. We evaluated the association between periodontal disease and CRP levels in adults in the Atherosclerosis Risk in Communities study. METHODS: Oral examinations were conducted between January 1, 1996, and December 31, 1998, on 5552 ARIC participants (aged 52-74 years) from 4 US communities. Periodontal disease was quantified as the percentage of periodontal sites with pocket depth of 4 mm or more. Serum CRP concentration was quantified in milligrams per liter using an enzyme-linked immunosorbent assay. RESULTS: Mean (SE) CRP level was 7.6 (0.6) mg/L among people with extensive periodontal pockets (>30% of sites with pocket depth > or =4 mm), approximately one-third greater than that for people with less extensive periodontal pockets (5.7 [0.1] mg/L). In a multivariable linear regression model that controlled for age, sex, diabetes mellitus, cigarette use, and nonsteroidal anti-inflammatory drug use, the association of extensive periodontal pockets with CRP concentration was modified by body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters). For people with a BMI of 20, the model predicted a 2-fold difference in mean CRP concentration between periodontal pocket groups (7.5 vs 3.6 mg/L), but the difference decreased with increasing BMI and was negligible when BMI equaled 35. CONCLUSIONS: Extensive periodontal disease and BMI are jointly associated with increased CRP levels in otherwise healthy, middle-aged adults, suggesting the need for medical and dental diagnoses when evaluating sources of acute-phase response in some patients.

Tooth loss, periodontal disease, and cognitive decline in the Atherosclerosis Risk in Communities (ARIC) study.

OBJECTIVE: The purpose of this prospective study was to investigate whether poor oral health predicted 8-year cognitive function change in predominantly late middle adults in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: Participants included a subset of ARIC participants aged 52-75 years at 1996-1998 from two study sites: Forsyth County NC and Jackson MS. All subjects completed cognitive function assessments both in 1996-1998 and 2004-2006, and the same subjects received a dental examination at the initial visit. Cognitive assessment consisted of delayed word recall (DWR), digit symbol substitution (DSS), and word fluency (WF) tests. In the analysis, cognitive function for 911 dentally screened participants was evaluated, and 558 of 785 dentate participants received comprehensive oral examinations, including periodontal probing. Measures of oral health included dental status, number of teeth, and periodontal disease classified by the biofilm-gingival interface (BGI) index. The generalized estimating equations (GEE) method was used to analyze repeated measures of cognitive scores with adjustment for socio-demographic characteristics and cardiovascular risk factors. RESULTS: Of 911 study participants, 13.8% were edentulous. About 13% of dentally examined participants had periodontal pockets (≥ 4 mm) with severe bleeding. At the follow-up visit, DWR and WF scores were lower in edentulous compared to dentate people, whereas other oral health measures were not associated with cognitive function. Mean values declined over time for all three cognitive measures, although poor oral health conditions were not associated with greater degree of decline in cognitive function. CONCLUSIONS: In these late middle-aged adults, complete tooth loss was significantly associated with lower cognitive performance. However, neither edentulism, number of teeth, nor periodontal disease predicted greater subsequent cognitive decline.

Cross-sectional associations of oral health measures with cognitive function in late middle-aged adults: a community-based study.

BACKGROUND: It has not been established to what extent oral health is associated with cognitive function in late middle-aged adults. In this study, which is part of the national Atherosclerosis Risk in Communities (ARIC) study, the authors investigated whether tooth loss and periodontitis are associated with lower cognitive function. METHODS: The authors analyzed ARIC data measuring cognitive function in 11,097 participants from 1996 through 1998 according to tests of delayed word recall, digit-symbol substitution (DSS) and word fluency; 9,874 participants answered dental screening questions. Of the 8,554 dentate participants, 5,942 received oral examinations. The authors used measures of dental status, number of teeth and periodontitis (classified according to the Biofilm-Gingival Interface Index) in multiple linear regression models to estimate these factors' cross-sectional association with cognitive scores, adjusting for sociodemographic factors, cigarette smoking, alcohol use and diabetes. RESULTS: Approximately 13 percent of participants were edentulous. Of the dentate participants, 27.3 percent had fewer than 20 teeth and 12.4 percent had pocket depth of 4 millimeters or more with severe bleeding. Compared with dentate participants, edentulous participants had lower scores for all cognitive tests. Among the dentate participants, having fewer teeth and gingival bleeding were associated with lower DSS and word fluency test scores, although periodontal pocket depth was not. CONCLUSIONS: In this cohort, edentulism was correlated with lower cognitive status. Tooth loss and gingival bleeding were markers of poorer executive function among dentate people. Practical Implications. The association of lower cognitive scores with edentulism suggests that past oral diseases may be a risk indicator for cognitive decline, whereas the association with gingival inflammation indicates a possible effect of cognitive decline on oral health. Practitioners should be aware that both current and historical markers of oral disease might be associated with decline in cognitive function, even in adults of late middle age.

Design and implementation of the Hispanic Community Health Study/Study of Latinos.

PURPOSE: The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a comprehensive multicenter community based cohort study of Hispanics/Latinos in the United States. METHODS: The Study rationale, objectives, design, and implementation are described in this report. RESULTS: The HCHS/SOL will recruit 16,000 men and women who self-identify as Hispanic or Latino, 18 to 74 years of age, from a random sample of households in defined communities in the Bronx, Chicago, Miami, and San Diego. The sites were selected so that the overall sample would consist of at least 2000 persons in each of the following origin designations: Mexican, Puerto Rican and Dominican, Cuban, and Central and South American. The study includes research in the prevalence of and risk factors for heart, lung, blood and sleep disorders, kidney and liver function, diabetes, cognitive function, dental conditions, and hearing disorders. CONCLUSIONS: The HCHS/SOL will (1) characterize the health status and disease burden in the largest minority population in the United States; (2) describe the positive and negative consequences of immigration and acculturation of Hispanics/Latinos to the mainstream United States life-styles, environment and health care opportunities; and (3) identify likely causal factors of many diseases in a population with diverse environmental exposures, genetic backgrounds, and early life experiences.

Socioeconomic disadvantage and periodontal disease: the Dental Atherosclerosis Risk in Communities study.

OBJECTIVES: We used data from the Dental Atherosclerosis Risk in Communities study to examine whether individual- and neighborhood-level socioeconomic characteristics were associated with periodontal disease. METHODS: We assessed severe periodontitis with a combination of clinical attachment loss and pocket depth measures. Marginal logistic regression modeling was used to estimate the association between individual and neighborhood socioeconomic indicators and prevalence of severe periodontitis before and after control for selected covariates. Residual intraneighborhood correlations in outcomes were taken into account in the analyses. RESULTS: Individual-level income and education were associated with severe periodontitis among Whites and African Americans, and these associations remained significant after adjustment for age, gender, recruitment center, and neighborhood socioeconomic score. Low-income Whites residing in disadvantaged neighborhoods had 1.8-fold (95% confidence interval=1.2, 2.7) higher odds of having severe periodontitis than high-income Whites residing in advantaged neighborhoods. CONCLUSIONS: Individual income and education were associated with severe periodontitis independently of neighborhood socioeconomic circumstances. Although the association between neighborhood socioeconomic status and severe periodontitis was not statistically significant, poverty and residence in a disadvantaged neighborhood were associated with higher odds of severe periodontitis among Whites.

Periodontal Disease and Cardiovascular Disease.

It is our central hypothesis that periodontal diseases, which are chronic Gramnegative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2 , IL-1ß, PGE2 , and TNF-α) which serve to initiate and exacerbate atherogenesis' and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease. J Periodontol 1996;67:1123-1137.