Clinical attachment loss is cross-sectionally associated with elevated glucose among adults without diabetes.

AIM: We investigated whether periodontal measures are cross-sectionally associated with prediabetes and cardiometabolic biomarkers among non-diabetic younger adults. MATERIALS AND METHODS: One thousand seventy-one participants (mean age = 32.2 years [SE = 0.3]; 73% female) from the Oral Infections, Glucose Intolerance and Insulin Resistance Study were enrolled. Full-mouth clinical attachment loss (fm-CAL), probing depth (fm-PD) and bleeding on probing were ascertained. Interproximal CAL (i-CAL) and probing depths (i-PD) served as our primary exposures. Glucose, HbA1c, insulin and insulin resistance (HOMA-IR) outcomes were assessed from fasting blood. Prediabetes was defined per American Diabetes Association guidelines. Prediabetes prevalence ratios (PR [95% CI]) and mean [SE] cardiometabolic biomarkers were regressed on periodontal variables via multivariable robust variance Poisson regression or multivariable linear regression. RESULTS: Prevalence of prediabetes was 12.5%. Fully adjusted prediabetes PR in Tertiles 3 versus 1 of mean i-CAL was 2.42 (1.77, 3.08). Fully adjusted fasting glucose estimates across i-CAL tertiles were 83.29 [0.43], 84.31 [0.37], 86.48 [0.46]; p for trend <.01. Greater percent of sites with i-PD ≥3 mm showed elevated natural-log-HOMA-IR after adjustment (0%-12% of sites = 0.33 [0.03], 13%-26% of sites = 0.39 [0.03], ≥27% of sites = 0.42 [0.03]; p for trend = .04). CONCLUSIONS: i-CAL (vs. fm-CAL) was associated with elevated fasting glucose and prediabetes, whereas i-PD (vs. fm-PD) was associated with insulin resistance. Future studies are needed to examine periodontal disease and incident prediabetes.

Periodontal diseases and carotid intima-media thickness in Bangladesh.

AIM: To evaluate the relationship between periodontal diseases and subclinical atherosclerosis in a younger and lean South Asian population. METHODS: We conducted a cross-sectional study in 917 subjects (mean age 46 years and mean body mass index 21.1 kg/m2 ) from the Health Effects of Arsenic Longitudinal Study in Bangladesh. Multivariate linear regression models were used to assess the associations between multiple clinical measures of periodontal diseases and carotid intima-media thickness (IMT). RESULTS: Mean attachment loss (AL) and percentage of sites with AL ≥ 4 mm (% AL ≥ 4) were associated with increased IMT. The IMT was 20.0-µm (95% CI: 2.2, 37.8) and 26.5-µm (95% CI: 8.9, 44.1) higher in subjects in the top quartile of mean AL (>3.72 mm) and % AL ≥ 4 (>58.4%), respectively, compared to those in the bottom quartile. In a subset of 366 subjects, mean AL was positively associated with plasma levels of matrix metalloproteinase-9 (p < 0.05) and soluble intercellular adhesion molecule-1 (p < 0.01). CONCLUSIONS: Attachment loss was associated with subclinical atherosclerosis in this young and lean Bangladeshi population. Future prospective studies are needed to confirm this association.

Periodontal infection, impaired fasting glucose and impaired glucose tolerance: results from the Continuous National Health and Nutrition Examination Survey 2009-2010.

AIM: We investigated the relationship between periodontal disease, a clinical manifestation of periodontal infection, and pre-diabetes. METHODS: The National Health and Nutrition Examination Survey, 2009-2010 enrolled 1165 diabetes-free adults (51% female) aged 30-80 years (mean ± SD=50 ± 14) who received a full-mouth periodontal examination and an oral glucose tolerance test. Participants were classified as having none/mild, moderate or severe periodontitis and also according to mean probing depth ≥ 2.19 mm or attachment loss ≥ 1.78 mm, (respective 75th percentiles). Pre-diabetes was defined according to ADA criteria as either: (i) impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). In multivariable logistic regression models, the odds of IFG and IGT were regressed on levels of periodontitis category. RESULTS: The odds ratios and 95% confidence intervals for having IGT among participants with moderate or severe periodontitis, relative to participants with none/mild periodontitis were 1.07 [0.50, 2.25] and 1.93 [1.18, 3.17], p = 0.02. The ORs for having IFG were 1.14 [0.74, 1.77] and 1.12 [0.58, 2.18], p = 0.84. PD ≥ 75 th percentile was related to a 105% increase in the odds of IGT: OR [95% CI] = 2.05 [1.24, 3.39], p = 0.005. CONCLUSIONS: Periodontal infection was positively associated with prevalent impaired glucose tolerance in a cross-sectional study among a nationally representative sample.

Effects of different manual periodontal probes on periodontal measurements.

AIM: To quantify the digit preference effect for three manual periodontal probes and to calculate correction values to enable comparison of studies with equal recording protocols, but different periodontal probes. MATERIAL AND METHODS: A prospective in vivo crossover study was conducted with a six-sequence three-period design. Six examiners assessed attachment loss (AL), probing pocket depth (PD) and gingiva height (GH) at four surfaces, full-mouth, in six generally healthy subjects using three manual probes: PCP11 (3-3-3-2 mm increments), PCP2 (2 mm increments), and PCPUNC15 (1 mm increments). RESULTS: Distributions of AL, PD and GH differed between probes (p < 0.001). Compared with PCPUNC15, periodontal measurements coinciding with probe markings of PCP11 and PCP2, respectively, were preferentially named by examiners. Digit preference was most pronounced for PD, but less for AL and GH. In multilevel models, PD differed significantly between all three probes (p < 0.05); probe- and examiner-related effects were also observed for AL and GH. Correction values for pairwise combinations of probes were determined. CONCLUSIONS: We provided empirical evidence and quantified the effect of probe type on periodontal measurements. Differences in probe type should be considered when comparing periodontal data within and between epidemiological studies and appropriate corrections, provided here, should be applied.

A comparison of periodontal status in the two regional, population-based studies of SHIP and INVEST.

OBJECTIVES: To compare the prevalence of periodontal disease between two randomly selected population-based studies (the Oral Infections and Vascular Disease Epidemiology Study (INVEST) and the Study of Health in Pomerania (SHIP)) and address relevant methodological issues. METHODS: Comparison was restricted to 55- to 81-year olds. Attachment loss (AL), probing depth (PD) and tooth count were assessed in INVEST (full-mouth, six sites) and SHIP (half-mouth, four sites). Subjects were classified according to the CDC/AAP case definition. Recording protocols were standardized. Mixed linear or logistic models were used to compare INVEST with SHIP. RESULTS: Mean half-mouth AL was lower in INVEST versus SHIP (INVEST: 2.9 mm versus SHIP: 4.0 mm, p < 0.05). Findings were similar across multiple periodontal disease definitions. After equalization of recording protocols and adjustment for periodontal risk factors, mean AL and PD were 1.2 and 0.3 mm lower in INVEST versus SHIP (p < 0.001). The odds for severe periodontitis (CDC/AAP) was 0.2-fold in INVEST versus SHIP (p < 0.001). Confounding effects of age, gender, race/ethnicity, education and use of interdental care devices were highest as indicated by change-in-estimate for study. CONCLUSION: Implementation of the proposed method for comparison of epidemiological studies revealed that periodontitis was less prevalent in INVEST compared with SHIP, even after extensive risk-factor adjustment.

Early microbial markers of periodontal and cardiometabolic diseases in ORIGINS.

Periodontitis affects up to 50% of individuals worldwide, and 8.5% are diagnosed with diabetes. The high-comorbidity rate of these diseases may suggest, at least in part, a shared etiology and pathophysiology. Changes in oral microbial communities have been documented in the context of severe periodontitis and diabetes, both independently and together. However, much less is known about the early oral microbial markers of these diseases. We used a subset of the ORIGINS project dataset, which collected detailed periodontal and cardiometabolic information from 787 healthy individuals, to identify early microbial markers of periodontitis and its association with markers of cardiometabolic health. Using state-of-the-art compositional data analysis tools, we identified the log-ratio of Treponema to Corynebacterium bacteria to be a novel Microbial Indicator of Periodontitis (MIP), and found that this MIP correlates with poor periodontal health and cardiometabolic markers early in disease pathogenesis in both subgingival plaque and saliva.

Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS.

Background The enterosalivary nitrate-nitrite-nitric oxide (NO3-NO2-NO) pathway generates NO following oral microbiota-mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross-sectionally. Methods and Results This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO2, NO, or ammonia [NH3]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation-to-depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic Z score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic Z score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH3 summary ratio was inversely associated with a -0.10 (false discovery rate q=0.003) lower composite cardiometabolic Z score in simple adjusted models. Higher NH3 summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate q=0.04) higher composite cardiometabolic Z score. Conclusions Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.

Associations between Pharmacotherapy for Cardiovascular Diseases and Periodontitis.

The goal of the study was to assess the relationship between cardioprotective medications, i.e., beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), statins, acetylsalicylic acid (ASA), and periodontitis (PD). BACKGROUND: Xerostomia increases the risk of PD and is a side effect of some pharmacotherapies. Information about the effect of cardioprotective treatment of periodontal status is scarce. METHODS: We studied 562 dentate residents of Krakow at the age of 50 to 70 years. Information about treatment was collected using a standardized questionnaire. The pocket depth and clinical attachment level (CAL) were used to ascertain PD. Multivariate logistic regression was applied to assess the relation between cardioprotective medications and PD. RESULTS: PD was found in 74% of participants. The range of cardioprotective drug use among participants was 7% (ARBs) to 32% (beta-blockers). After adjusting for age, sex, number of teeth, smoking, and education, ASA's use was related to a lower prevalence of PD in all dentate participants (odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.40-0.99). The use of ARBs and statins was found to be associated with a higher prevalence of PD in persons having ≥6 teeth (odds ratio (OR) = 3.57, 95% CI: 1.06-11.99 and OR = 1.81, 95% CI: 1.03-3.16, respectively). Further adjustment for CVD risk factors, history of coronary heart disease, and other chronic diseases did not attenuate the results. There was no significant relation between PD and the use of other cardioprotective drugs.

Evaluating clinical periodontal measures as surrogates for bacterial exposure: the Oral Infections and Vascular Disease Epidemiology Study (INVEST).

BACKGROUND: Epidemiologic studies of periodontal infection as a risk factor for cardiovascular disease often use clinical periodontal measures as a surrogate for the underlying bacterial exposure of interest. There are currently no methodological studies evaluating which clinical periodontal measures best reflect the levels of subgingival bacterial colonization in population-based settings. We investigated the characteristics of clinical periodontal definitions that were most representative of exposure to bacterial species that are believed to be either markers, or themselves etiologic, of periodontal disease. METHODS: 706 men and women aged >or= 55 years, residing in northern Manhattan were enrolled. Using DNA-DNA checkerboard hybridization in subgingival biofilms, standardized values for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia were averaged within mouth and summed to define "bacterial burden". Correlations of bacterial burden with clinical periodontal constructs defined by the severity and extent of attachment loss (AL), pocket depth (PD) and bleeding on probing (BOP) were assessed. RESULTS: Clinical periodontal constructs demonstrating the highest correlations with bacterial burden were: i) percent of sites with BOP (r = 0.62); ii) percent of sites with PD >or= 3 mm (r = 0.61); and iii) number of sites with BOP (r = 0.59). Increasing PD or AL severity thresholds consistently attenuated correlations, i.e., the correlation of bacterial burden with the percent of sites with PD >or= 8 mm was only r = 0.16. CONCLUSIONS: Clinical exposure definitions of periodontal disease should incorporate relatively shallow pockets to best reflect whole mouth exposure to bacterial burden.

Prevalence of periodontal disease and treatment demands based on a German dental survey (DMS IV).

AIM: We assessed the prevalence and extent of periodontitis in Germany. Furthermore, region- and gender-specific differences in periodontal disease prevalence were evaluated. MATERIAL AND METHODS: The fourth German Dental Health Survey is a national cross-sectional survey conducted in 2005. Nine hundred and twenty-five adults (35-44 years) and 1040 seniors (65-74 years) were examined. The survey comprised social- and health-related interviews and dental examinations. Probing depth (PD) and clinical attachment loss (CAL) were assessed at three sites at 12 index teeth. RESULTS: Prevalence of CAL> or =3 mm was found in 95.0% in adults and 99.2% in seniors with 68.7% and 91.4% of teeth being affected, respectively. PD> or =4 mm was prevalent in 76.9% and 87.7% in both age groups, respectively. According to the CDC definition considering mesiobuccal and distolingual sites, prevalence of periodontitis was 70.9% and 87.4% in both age cohorts, with one-fourth and one-half presenting severe forms, respectively. Periodontal prevalence was significantly higher in male subjects and East German subjects. CONCLUSIONS: Periodontitis was highly prevalent in German adults. To reduce periodontal burden, treatment of periodontal diseases and continuous maintenance should become an integral part in dental practice. Furthermore, health recommendations should be implemented at the community, professional, and individual level.

Association Between Nitrate-Reducing Oral Bacteria and Cardiometabolic Outcomes: Results From ORIGINS.

Background The enterosalivary nitrate-nitrite-nitric oxide pathway is an alternative pathway of nitric oxide generation, potentially linking the oral microbiome to insulin resistance and blood pressure (BP). We hypothesized that increased abundance of nitrate-reducing oral bacteria would be associated with lower levels of cardiometabolic risk cross-sectionally. Methods and Results ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study) enrolled 300 diabetes mellitus-free adults aged 20 to 55 years (mean=34±10 years) (78% women). Microbial DNA was extracted from subgingival dental plaque (n=281) and V3-V4 regions of the 16S rRNA gene were sequenced to measure the relative abundances of 20 a priori-selected taxa with nitrate-reducing capacity. Standardized scores of each taxon's relative abundance were summed, producing a nitrate-reducing taxa summary score (NO3TSS) for each participant. Natural log-transformed homeostatic model assessment of insulin resistance, plasma glucose, systolic BP, and diastolic BP were regressed on NO3TSS in multivariable linear regressions; prediabetes mellitus and hypertension prevalence were regressed on NO3TSS using modified Poisson regression models. Nitrate-reducing bacterial species represented 20±16% of all measured taxa. After multivariable adjustment, a 1-SD increase in NO3TSS, was associated with a -0.09 (95% CI, -0.15 to -0.03) and -1.03 mg/dL (95% CI, -1.903 to -0.16) lower natural log-transformed homeostatic model assessment of insulin resistance and plasma glucose, respectively. NO3TSS was associated with systolic BP only among patients without hypertension; 1-SD increase in NO3TSS was associated with -1.53 (95% CI, -2.82 to -0.24) mm Hg lower mean systolic BP. No associations were observed with prediabetes mellitus and hypertension. Conclusions A higher relative abundance of oral nitrate-reducing bacteria was associated with lower insulin resistance and plasma glucose in the full cohort and with mean systolic BP in participants with normotension.

Bleeding on probing differentially relates to bacterial profiles: the Oral Infections and Vascular Disease Epidemiology Study.

AIM: Various bacterial species are differentially prevalent in periodontal health, gingivitis or periodontitis. We tested the independent associations between three bacterial groupings and gingival inflammation in an epidemiological study. MATERIAL AND METHODS: In 706 Oral Infections and Vascular Disease Epidemiology Study (INVEST) participants > or =55 years, bleeding on probing (BoP), pocket depth (PD) and subgingival plaque samples (n=4866) were assessed in eight sites per mouth. Eleven bacterial species were quantitatively assayed and grouped as follows: (i) aetiologic burden (EB, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia); (ii) putative burden (PB, Campylobacter rectus, Eikenella corrodens, Fusobacterium nucleatum, Micromonas micros, Prevotella intermedia); (iii) health-associated burden (HAB, Actinomyces naeslundii, Veillonella parvula). RESULTS: After mutual adjustment for EB, PB and HAB, the BoP prevalence increased by 45% ( p<0.0001) across increasing quartiles of EB while BoP decreased by 13% ( p<0.0001) across increasing quartiles of HAB. Mean PD increased 0.8 mm and decreased 0.3 mm from the first to fourth quartiles of EB (p<0.0001) and HAB ( p<0.0001), respectively. Among 1214 plaque samples with fourth quartile EB, 60% were collected from sites with PD < or =3 mm. CONCLUSION: Bacterial species believed to be aetiologically related to periodontitis were associated with BoP in sites with minimal PD and/or attachment level (AL). Species presumed to be associated with periodontal health demonstrated inverse associations with BoP.

Prevalence and quality of endodontic treatment in the Northern Manhattan elderly.

Pulpitis results in significant morbidity among the elderly, particularly in underserved communities. We collected panoramic oral radiographs from 244 (mean age 67) participants of the Northern Manhattan Study, a prospective cohort study of stroke risk in a multiethnic urban population. Radiographs were evaluated for missing teeth, caries, restorations, periodontal bone loss, adequacy of endodontic treatment, and periapical radiolucencies. In the study 206 subjects were dentate (mean 17.1 teeth). 5.1% of teeth had periapical radiolucencies, and 4.8% had been endodontically treated; 37.5% of endodontically treated teeth had periapical radiolucencies. Teeth with restorations, periodontal bone loss, pulpotomy, and inadequate root canal filling had a significantly higher occurrence of periapical radiolucency (p < 0.05). Among all root filled teeth, only 26% were deemed satisfactory. We conclude that apical periodontitis is widely prevalent and the technical standard of root fillings is poor in this cohort. There is a substantial need for improved dental care among the northern Manhattan elderly.

Periodontal microbiota and carotid intima-media thickness: the Oral Infections and Vascular Disease Epidemiology Study (INVEST).

BACKGROUND: Chronic infections, including periodontal infections, may predispose to cardiovascular disease. We investigated the relationship between periodontal microbiota and subclinical atherosclerosis. METHODS AND RESULTS: Of 1056 persons (age 69+/-9 years) with no history of stroke or myocardial infarction enrolled in the Oral Infections and Vascular Disease Epidemiology Study (INVEST), we analyzed 657 dentate subjects. Among these subjects, 4561 subgingival plaque samples were collected (average of 7 samples/subject) and quantitatively assessed for 11 known periodontal bacteria by DNA-DNA checkerboard hybridization. Extensive in-person cardiovascular risk factor measurements, a carotid scan with high-resolution B-mode ultrasound, white blood cell count, and C-reactive protein values were obtained. In 3 separate analyses, mean carotid artery intima-media thickness (IMT) was regressed on tertiles of (1) burden of all bacteria assessed, (2) burden of bacteria causative of periodontal disease (etiologic bacterial burden), and (3) the relative predominance of causative/over other bacteria in the subgingival plaque. All analyses were adjusted for age, race/ethnicity, gender, education, body mass index, smoking, diabetes, systolic blood pressure, and LDL and HDL cholesterol. Overall periodontal bacterial burden was related to carotid IMT. This relationship was specific to causative bacterial burden and the dominance of etiologic bacteria in the observed microbiological niche. Adjusted mean IMT values across tertiles of etiologic bacterial dominance were 0.84, 0.85, and 0.88 (P=0.002). Similarly, white blood cell values increased across tertiles of etiologic bacterial burden from 5.57 to 6.09 and 6.03 cells x10(9)/L (P=0.01). C-reactive protein values were unrelated to periodontal microbial status (P=0.82). CONCLUSIONS: Our data provide evidence of a direct relationship between periodontal microbiology and subclinical atherosclerosis. This relationship exists independent of C-reactive protein.

Periodontal infections and cardiovascular disease: the heart of the matter.

BACKGROUND: Oral infection models have emerged as useful tools to study the hypothesis that infection is a cardiovascular disease (CVD) risk factor. Periodontal infections are a leading culprit, with studies reporting associations between periodontal disease and CVD. The results, however, have varied, and it often is unclear what conclusions can be drawn from these data. SUMMARY: An association exists between periodontal disease and CVD. It is unknown, however, whether this relationship is causal or coincidental. Early studies predominantly used nonspecific clinical and radiographic definitions of periodontal disease as surrogates for infectious exposure. While most studies demonstrated positive associations between periodontal disease and CVD, not all studies were positive, and substantial variations in results were evident. More recent studies have enhanced the specificity of infectious exposure definitions by measuring systemic antibodies to selected periodontal pathogens or by directly measuring and quantifying oral microbiota from subgingival dental plaque. Results from these studies have shown positive associations between periodontal disease and CVD. CONCLUSIONS: Evidence continues to support an association among periodontal infections, atherosclerosis and vascular disease. Ongoing observational and focused pilot intervention studies may inform the design of large-scale clinical intervention studies. Recommending periodontal treatment for the prevention of atherosclerotic CVD is not warranted based on scientific evidence. Periodontal treatment must be recommended on the basis of the value of its benefits for the oral health of patients, recognizing that patients are not healthy without good oral health. However, the emergence of periodontal infections as a potential risk factor for CVD is leading to a convergence in oral and medical care that can only benefit the patients and public health.

Radiographic measures of chronic periodontitis and carotid artery plaque.

BACKGROUND AND PURPOSE: Chronic periodontitis (CP) is associated with stroke and subclinical atherosclerosis, but clinical measurement of CP can be time consuming and invasive. The purpose of this study was to determine whether radiographically assessed CP is associated with nonstenotic carotid artery plaque as an ultrasound measure of subclinical atherosclerosis. METHODS: Panoramic oral radiographs were obtained from 203 stroke-free subjects ages 54 to 94 during the baseline examination of the Oral Infections and Vascular Disease Epidemiology Study (INVEST). CP exposure among dentate subjects was defined either categorically (periodontal bone loss > or =50% [severe] versus <50% bone loss) or via tertile formation (for dose-response investigation), with edentulous subjects categorized separately. In all subjects, high-resolution B-mode carotid ultrasound was performed. Carotid plaque thickness (CPT) and prevalence (present/absent) were recorded. Covariates included age, sex, smoking, diabetes, hypertension, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol. RESULTS: Among dentate subjects with severe periodontal bone loss, mean CPT was significantly greater (1.20+/-1.00 mm versus 0.73+/-0.89 mm; P=0.003). CPT increased with more severe bone loss (upper versus lower tertile bone loss; P=0.049; adjusted for age, sex, and hypertension). This apparent dose-response effect was more evident among never-smokers. In a fully adjusted multivariate logistic regression model, severe periodontal bone loss was associated with a nearly 4-fold increase in risk for the presence of carotid artery plaque (adjusted odds ratio, 3.64; CI, 1.37 to 9.65). CONCLUSIONS: Severe periodontal bone loss is associated independently with carotid atherosclerosis. Panoramic oral radiographs may thus provide an efficient means to assess CP in studies of atherosclerosis risk.

Periodontal microbiota and phospholipases: the Oral Infections and Vascular Disease Epidemiology Study (INVEST).

OBJECTIVE: Periodontal infections have been linked to cardiovascular disease, including atherosclerosis, and systemic inflammation has been proposed as a possible mediator. Secretory phospholipase A2 (s-PLA2) and Lipoprotein-associated PLA2 (Lp-PLA2) are inflammatory enzymes associated with atherosclerosis. No data are available on the association between oral microbiota and PLA2s. We studied whether a relationship exists between periodontal microbiota and the activities of these enzymes. METHODS: The Oral Infection and Vascular Disease Epidemiology Study (INVEST) collected subgingival biofilms and serum samples from 593 dentate men and women (age 68.7 ± 8.6 years). 4561 biofilm samples were collected in the two most posterior teeth of each quadrant (average 7/participant) for quantitative assessment of 11 bacterial species using DNA-DNA checkerboard hybridization. Mean concentration of s-PLA2 and activities of s-PLA2 and Lp-PLA2 were regressed on tertiles of etiologic dominance (ED). ED is defined as the level of presumed periodontopathic species/combined level of all eleven species measured, and represents the relative abundance of periodontopathic organisms. Analyses were adjusted for age, sex, race/ethnicity, education, smoking, BMI, diabetes, LDL cholesterol and HDL cholesterol, and systolic blood pressure. RESULTS: Higher levels of s-PLA2 activity were observed across increasing tertiles of etiologic dominance (0.66 ± 0.04 nmol ml(-1) min(-1), 0.73 ± 0.04 nmol ml(-1) min(-1), 0.89 ± 0.04 nmol ml-1 min-1; p < 0.001), with also a trend of association between Lp-PLA2 activity and ED (p = 0.07), while s-PLA2 concentration was unrelated to ED. CONCLUSION: Increasingly greater s-PLA2 activity at higher tertiles of etiologic dominance may provide a mechanistic explanatory link of the relationship between periodontal microbiota and vascular diseases. Additional studies investigating the role of s-PLA2 are needed.

Relationship between periodontal disease, tooth loss, and carotid artery plaque: the Oral Infections and Vascular Disease Epidemiology Study (INVEST).

BACKGROUND AND PURPOSE: Chronic infections, including periodontal infections, may predispose to cardiovascular disease. The present study investigates the relationship of periodontal disease and tooth loss with subclinical atherosclerosis. METHODS: We enrolled 711 subjects with a mean age of 66+/-9 years and no history of stroke or myocardial infarction in the Oral Infections and Vascular Disease Epidemiology Study. Subjects received a comprehensive periodontal examination, extensive in-person cardiovascular disease risk factor measurements, and a carotid scan using high-resolution B-mode ultrasound. Regression models were adjusted for conventional risk factors (age, sex, smoking, diabetes, systolic blood pressure, low- and high-density lipoprotein cholesterol, race-ethnicity, education, physical activity) and markers of cultural background, healthy lifestyle, and psychosocial health. RESULTS: Measures of both current and cumulative periodontitis became more severe as tooth loss increased. A significant association was observed between tooth loss levels and carotid artery plaque prevalence. Among those with 0 to 9 missing teeth, 46% had carotid artery plaque, whereas among those with >or=10 missing teeth, carotid artery plaque prevalence was approximately 60% (P<0.05). CONCLUSIONS: Our data suggest that tooth loss is a marker of past periodontal disease in this population and is related to subclinical atherosclerosis, thereby providing a potential pathway for a relationship with clinical events.

Gender differences in the relationship between periodontal disease, tooth loss, and atherosclerosis.

BACKGROUND AND PURPOSE: Males carry a disproportionate burden of cardiovascular disease. Because males also bear a higher burden of periodontal disease, we investigated the existence of gender differences in the postulated relationship between periodontal infections, tooth loss, and subclinical atherosclerosis. METHODS: A total of 1710 randomly enrolled participants between the ages of 45 and 75 with no history of myocardial infarction or stroke received a clinical periodontal examination, carotid scan using high-resolution B-mode ultrasound, and extensive measurements for conventional cardiovascular risk factors (age, education, smoking, alcohol, body mass index, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides) as well as markers of healthy lifestyle and social network. RESULTS: In both genders, measures of current and long-term periodontitis worsened as tooth loss increased. In males but not females, an approximately 10% difference in carotid artery plaque prevalence was observed between the lowest and highest tertiles of tooth loss (P<0.05) and long-term periodontitis (P=0.05) after multivariate adjustment. Similar patterns were observed for intima-media thickness. The influence of gender on carotid artery plaque prevalence was most evident among the younger age group (<59 years). Between genders, carotid plaque prevalence differed by 10%, 15%, and 25% across increasing levels of tooth loss, and by 5%, 15%, and 25% across increasing levels of long-term periodontitis. CONCLUSIONS: Our data suggest that tooth loss and long-term periodontitis are related to subclinical atherosclerosis in men but not women. Gender variations in cardiovascular morbidity or mortality may be explained partly by the differential contributions of novel risk factors across genders.

Periodontitis and coronary artery calcification: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Periodontitis has been linked to coronary heart disease (CHD) risk, possibly through providing a systemic inflammatory burden. Few studies have evaluated periodontitis and subclinical measures of atherosclerosis. Coronary artery calcification (CAC) is an emerging marker for atherosclerosis, and past studies suggest that it predicts incident CHD in asymptomatic populations. METHODS: In 1996-1998, dental examinations were performed on 6,931 participants in the Atherosclerosis Risk in Communities (ARIC) cohort. Extent of periodontitis was measured by the percent of sites with attachment level (AL) > or = 3 mm. In 1999-2000, CAC was measured by cardiac gated mechanical or helical computed tomography in 269 dental examinees and edentulous subjects from the Minnesota and North Carolina field centers of ARIC who were free of clinically recognized CHD. A traditional Agatston score for CAC was calculated. RESULTS: Compared to subjects with no or mild periodontitis (<10% of sites with AL > or = 3 mm), subjects with moderate or severe periodontitis (> or = 10% of sites with AL > or = 3 mm) were more likely to have CAC > or = 100, but this difference was not statistically significant (odds ratio [OR]: 1.78; 95% confidence interval [CI]: 0.65 to 4.86). This association was partially but not completely attenuated when adjusted for demographic factors and traditional CHD risk factors (OR: 1.51; 95% CI: 0.54 to 4.23). CONCLUSIONS: These results suggest that periodontitis is not strongly associated with CAC. This study offers some reference for the magnitude of the association between CAC and periodontitis and information regarding the minimal power necessary for future studies.