James D. Beck

Acute-phase Inflammatory Response to Periodontal Disease in the US Population

Moderate elevation of serum C-reactive protein (CRP) is a risk factor for cardiovascular disease among apparently healthy individuals, although factors that create this inflammatory response in the absence of systemic illness have not been clarified. This study aimed to: (1) evaluate associations among periodontal disease, established risk factors for elevated CRP, and CRP levels within the US population; and (2) determine whether total tooth loss is associated with reduced CRP. Data were obtained from the third National Health and Nutrition Examination Survey. A random sample of the US population was interviewed in their homes and examined at mobile examination centers. CRP was quantified from peripheral blood samples and analyzed as a continuous variable and as the prevalence of elevated CRP (≥ 10 mg/L). Some 12,949 people aged 18+ years who had periodontal examinations and an additional 1817 edentulous people aged 18+ years were included in the analysis. Dentate people with extensive periodontal disease (> 10% of sites with periodontal pockets 4+ mm) had an increase of approximately one-third in mean CRP and a doubling in prevalence of elevated CRP compared with periodontally healthy people. Raised CRP levels among people with extensive periodontal disease persisted in multivariate analyses (P < 0.01), with established risk factors for elevated CRP (diabetes, arthritis, emphysema, smoking, and anti-inflammatory medications) and sociodemographic factors controlled for. However, CRP levels were similarly raised in edentulous people. Furthermore, the established risk factors for elevated CRP modified relationships between oral status and CRP levels. Periodontal disease and edentulism were associated with systemic inflammatory response in the US population, most notably among people who had no established risk factors for elevated CRP.

Update on Prevalence of Periodontitis in Adults in the United States: NHANES 2009 to 2012

BACKGROUND This report describes prevalence, severity, and extent of periodontitis in the US adult population using combined data from the 2009 to 2010 and 2011 to 2012 cycles of the National Health and Nutrition Examination Survey (NHANES). METHODS Estimates were derived for dentate adults, aged ≥30 years, from the US civilian non-institutionalized population. Periodontitis was defined by combinations of clinical attachment loss (AL) and periodontal probing depth (PD) from six sites per tooth on all teeth, except third molars, using standard surveillance case definitions. For the first time in NHANES history, sufficient numbers of non-Hispanic Asians were sampled in 2011 to 2012 to provide reliable estimates of their periodontitis prevalence. RESULTS In 2009 to 2012, 46% of US adults, representing 64.7 million people, had periodontitis, with 8.9% having severe periodontitis. Overall, 3.8% of all periodontal sites (10.6% of all teeth) had PD ≥4 mm, and 19.3% of sites (37.4% teeth) had AL ≥3 mm. Periodontitis prevalence was positively associated with increasing age and was higher among males. Periodontitis prevalence was highest in Hispanics (63.5%) and non-Hispanic blacks (59.1%), followed by non-Hispanic Asian Americans (50.0%), and lowest in non-Hispanic whites (40.8%). Prevalence varied two-fold between the lowest and highest levels of socioeconomic status, whether defined by poverty or education. CONCLUSIONS This study confirms a high prevalence of periodontitis in US adults aged ≥30 years, with almost fifty-percent affected. The prevalence was greater in non-Hispanic Asians than non-Hispanic whites, although lower than other minorities. The distribution provides valuable information for population-based action to prevent or manage periodontitis in US adults.

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.

Systemic effects of periodontitis: epidemiology of periodontal disease and cardiovascular disease.

There have been 42 published studies describing associations between oral conditions and cardiovascular diseases. In the absence of randomized controlled trials, the 16 longitudinal studies represent the highest level of evidence available. However, two databases produced eight of the 16 studies. There also is extensive variability in definitions of the oral exposure that include salivary flow, reported periodontal disease, number of teeth, oral organisms, antibodies to oral organisms, Total Dental Index, Community Periodontal Index of Treatment Needs, plaque scores, probing depth, attachment loss, and bone level. Variability also exists in the cardiovascular outcomes that include atherosclerosis measures and events, such as hospitalization for coronary heart disease (CHD), chronic CHD, fatal CHD, total stroke, ischemic stroke, and revascularization procedures. One of the criticisms of this research is that the exposure has not been represented by measures of infection. To begin to address this concern, we present new data showing that patterns of high and low levels of eight periodontal pathogens and antibody levels against those organisms are related to clinical periodontal disease as well as other characteristics of the individuals, such as age, race, gender, diabetic status, atherosclerosis, and CHD. As others before us, we conclude that the cumulative evidence presented above supports, but does not prove, a causal association between periodontal infection and atherosclerotic cardiovascular disease or its sequelae. A number of legitimate concerns have arisen about the nature of the relationship and, indeed, the appropriate definitions for periodontal disease when it is thought to be an exposure for systemic diseases. There is still much work needed to identify which aspects of the exposure are related to which aspects of the outcome. Principal component analyses illustrate the complexity of the interactions among risk factors, exposures, and outcomes. These analyses provide an initial clustering that describes and suggests the presence of specific syndromes.

Progressive Periodontal Disease and Risk of Very Preterm Delivery

OBJECTIVE: The goal was to estimate whether maternal periodontal disease was predictive of preterm (less than 37 weeks) or very preterm (less than 32 weeks) births. METHODS: A prospective study of obstetric outcomes, entitled Oral Conditions and Pregnancy (OCAP), was conducted with 1,020 pregnant women who received both an antepartum and postpartum periodontal examination. Predictive models were developed to estimate whether maternal exposure to either periodontal disease at enrollment (less than 26 weeks) and/or periodontal disease progression during pregnancy, as determined by comparing postpartum with antepartum status, were predictive of preterm or very preterm births, adjusting for risk factors including previous preterm delivery, race, smoking, social domain variables, and other infections. RESULTS: Incidence of preterm birth was 11.2% among periodontally healthy women, compared with 28.6% in women with moderate-severe periodontal disease (adjusted risk ratio [RR] 1.6, 95% confidence interval [CI] 1.1–2.3). Antepartum moderate-severe periodontal disease was associated with an increased incidence of spontaneous preterm births (15.2% versus 24.9%, adjusted RR 2.0, 95% CI 1.2–3.2). Similarly, the unadjusted rate of very preterm delivery was 6.4% among women with periodontal disease progression, significantly higher than the 1.8% rate among women without disease progression (adjusted RR 2.4, 95% CI 1.1–5.2). CONCLUSION: The OCAP study demonstrates that maternal periodontal disease increases relative risk for preterm or spontaneous preterm births. Furthermore, periodontal disease progression during pregnancy was a predictor of the more severe adverse pregnancy outcome of very preterm birth, independently of traditional obstetric, periodontal, and social domain risk factors. LEVEL OF EVIDENCE: II-2

Variations in the social impact of oral conditions among older adults in South Australia, Ontario, and North Carolina.

Previous studies among older adults have demonstrated that oral disease frequently leads to dysfunction, discomfort, and disability. This study aimed to assess variations in the social impact of oral conditions among six strata of people aged 65 years and older: residents of metropolitan Adelaide and rural Mt Gambier, South Australia; residents of metropolitan Toronto-North York and non-metropolitan Simcoe-Sudbury counties, Ontario, Canada; and blacks and whites in the Piedmont region of North Carolina (NC), United States. Subjects were participants in three oral epidemiological studies of random samples of the elderly populations in the six strata. Some 1,642 participants completed a 49-item Oral Health Impact Profile (OHIP) questionnaire which asked about impacts caused by problems with the teeth, mouth, or dentures during the previous 12 months. The percentage of dentate people reporting impacts fairly often or very often was greatest among NC blacks for 41 of the OHIP items. Two summary variables of social impact were used as dependent variables in bivariate and multivariate least-squares regression analyses. Among dentate people, mean levels of social impact were greatest for NC blacks and lowest for NC whites, while people from South Australia and Ontario had intermediate levels of social impact (P < 0.01). Missing teeth, retained root fragments, root-surface decay, periodontal pockets, and problem-motivated dental visits were associated with higher levels of social impact (P < 0.05), although there persisted a two-fold difference in social impact across the six strata after adjustment for those factors. Among edentulous people, there was no statistically significant variation in social impact among strata. The findings suggest that there are social and cultural factors influencing oral health and its social impact, and that those factors differ most between dentate blacks and whites in NC.

Dental infections and atherosclerosis

In most countries, coronary heart disease is one of the leading causes of morbidity and death. This report reviews the current evidence indicating that oral conditions (specifically periodontitis) may be a risk factor for atherosclerosis and its clinical manifestations and provides new preliminary data. This review is done in the context of the research indicating that inflammation plays a central role in atherogenesis and that there is a substantial systemic microbial and inflammatory burden associated with periodontal disease. Our review concentrates on 5 longitudinal studies that show oral conditions being associated with the onset of coronary heart disease while controlling for a variety of established coronary heart disease risk factors. In addition to published evidence, preliminary findings from our Dental Atherosclerosis Risk in Communities study also indicate that periodontal disease is associated with carotid intimal-medial wall thickness, a measure of subclinical atherosclerosis, adjusting for factors known to be associated with both conditions.

Exploratory Case‐Control Analysis of Psychosocial Factors and Adult Periodontitis

We explored the association between social factors and adult periodontitis by comparing self-reported information for daily strains and symptoms of depression in 71 cases and 77 controls. Cases and controls were selected from among 1,426 participants in the Erie County Risk Factor Study. We found differences among those who scored higher than their peers on measures of social strain. The odds ratio (OR) and 95% confidence interval (95% CI) for the association between case status and Role Strain score of 2.27 or more was 2.84, 95% CI = 1.08 to 7.46. We also examined serum antibody, dichotomized at the median, for three periodontal pathogens (Bacteroides forsythus [IgG Bf], Porphyromonas gingivalis [IgG Pg], Actinobacillus actinomycetemcomitans [IgG Aa]), and assessed interaction between antibody levels and a Depression score derived from the Brief Symptom Inventory. IgG Pg and IgG Aa were both strongly associated with case status (OR = 4.52, 95% CI = 1.99 to 10.3 and OR = 5.29, 95% CI = 2.34 to 12.0, respectively). IgG Bf was associated with periodontal disease but only among individuals who had higher scores for Depression (OR = 6.75, 95% CI = 1.25 to 36.5). Smoking status was associated with case status (OR = 4.95, 95% CI = 1.86 to 13.2). We assessed these findings prospectively by examining factors associated with more extensive disease among the 71 case subjects after 1 year of follow-up. We found baseline smoking status and IgG Bf among individuals scoring high on Depression at baseline to be associated with more extensive disease (8.1% or more of the sites showing further breakdown). In this population an elevated Depression score may be a marker for social isolation, which could play a role in immune function during periods of social strain. This exploratory analysis has served to identify specific lines of inquiry concerning psychosocial measures as important environmental factors in adult periodontitis. J Periodontol 1996;67:1060-1069.

Effects of periodontal therapy on rate of preterm delivery: A randomized controlled trial

OBJECTIVE: To test the effects of maternal periodontal disease treatment on the incidence of preterm birth (delivery before 37 weeks of gestation). METHODS: The Maternal Oral Therapy to Reduce Obstetric Risk Study was a randomized, treatment-masked, controlled clinical trial of pregnant women with periodontal disease who were receiving standard obstetric care. Participants were assigned to either a periodontal treatment arm, consisting of scaling and root planing early in the second trimester, or a delayed treatment arm that provided periodontal care after delivery. Pregnancy and maternal periodontal status were followed to delivery and neonatal outcomes until discharge. The primary outcome (gestational age less than 37 weeks) and the secondary outcome (gestational age less than 35 weeks) were analyzed using a χ2 test of equality of two proportions. RESULTS: The study randomized 1,806 patients at three performance sites and completed 1,760 evaluable patients. At baseline, there were no differences comparing the treatment and control arms for any of the periodontal or obstetric measures. The rate of preterm delivery for the treatment group was 13.1% and 11.5% for the control group (P=.316). There were no significant differences when comparing women in the treatment group with those in the control group with regard to the adverse event rate or the major obstetric and neonatal outcomes. CONCLUSION: Periodontal therapy did not reduce the incidence of preterm delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00097656. LEVEL OF EVIDENCE: I

Methods of assessing risk for periodontitis and developing multifactorial models.

In assessing risk for disease, periodontitis can be thought to be more like some of our common medical conditions: certain people are at higher risk than others, and efforts at prevention and intervention involve a combination of personal behaviors and professional practices. This paper presents some principles of designing risk assessment studies. In addition, the choices that must be made in deciding what is high risk and the type of model to be constructed are presented along with implications of each alternative. Terms such as risk indicators, risk factors, risk predictors, risk models, and prediction models are presented and discussed. To illustrate some of the issues, findings from the Piedmont 65+ Dental Study (a longitudinal study of oral health in older adults) indicate that: 1) indicators of risk developed from cross-sectional studies quite often are not confirmed as risk factors in longitudinal studies and longitudinal data implicate additional factors; 2) oral risk factors were important in explaining disease progression, but other categories of risk factors also played an explanatory role; 3) the risk models were able to predict who would experience attachment loss at some time during the 3-year period with a high degree of accuracy, but there was only moderate success at predicting who would not experience attachment loss; 4) including risk predictors in the models did improve the ability of one model to predict attachment loss, but the risk predictor masked the presence of an important risk factor; and 5) it is highly likely that adding measures of host defense mechanism to the study could result in improved models. J Periodontol 1994;65:468-478.