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.

Postmenopausal women with HIV have increased tooth loss.

BACKGROUND: With effective antiretroviral therapy, people with HIV (PWH) are living longer and aging; the majority of PWH in the United States are now over the age of 50 and in women have gone through the menopause transition. Menopause potentiates skeletal bone loss at the spine, hip, and radius in PWH. The alveolar bone which surronds the teeth is different than long bones because it is derived from the neural crest. However, few studies have assessed the oral health and alveolar bone in middle aged and older women with HIV. Therefore, the objective of this study was to evaluate periodontal disease and alveolar bone microarchitecture in postmenopausal women with HIV. METHODS: 135 self-reported postmenopausal women were recruited (59 HIV-, 76 HIV + on combination antiretroviral therapy with virological suppression) from a single academic center. The following parameters were measured: cytokine levels (IFN-γ, TNF-α, IL-1ß, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17 A, OPG, and RANKL) in gingival crevicular fluid, bleeding on probing, probing depth, clinical attachment loss, number of teeth present, alveolar crestal height, and alveolar bone microarchitecture. RESULTS: The mean age of participants was 57.04+/-6.25 years and a greater proportion of women with HIV were black/African American (HIV + 68.42%, HIV- 23.73%; p < 0.001). There was no significant difference in bleeding on probing (p = 0.17) and attachment loss (p = 0.39) between women who were HIV infected vs. HIV uninfected. Women with HIV had significantly higher RANKL expression in Gingival Crevicular Fluid (HIV + 3.80+/-3.19 pg/ul, HIV- 1.29+/-2.14 pg/ul ; p < 0.001), fewer teeth present (HIV + 17.75+/-7.62, HIV- 22.79+/-5.70; p < 0.001), ), lower trabecular number (HIV + 0.08+/-0.01, HIV- 0.09+/-0.02; p = 0.004) and greater trabecular separation (HIV + 9.23+/-3.11, HIV- 7.99+/-3.23; p = 0.04) compared to women without HIV that remained significant in multivariate logistic regression analysis in a sub-cohort after adjusting for age, race/ethnicity, smoking status, and diabetes. CONCLUSION: Postmenopausal women with HIV have deterioration of the alveolar trabecular bone microarchitecture that may contribute to greater tooth loss.

Evaluation of the mandibular condylar bone microarchitecture in people living with HIV.

OBJECTIVES: People living with HIV (PLWH) have been shown to have lower bone density at the spine, hip, and radius. However, whether a similar bone phenotype is seen in craniofacial bones is not known. The goal of this study was to evaluate the bone microarchitecture of the mandibular condyle in PLWH. METHODS: We recruited 212 participants, which included 88 HIV-negative participants and 124 PLWH on combination antiretroviral therapy with virological suppression from a single academic center. Each participant filled out a validated temporomandibular disorder (TMD) pain screening questionnaire and had cone beam computed tomography (CBCT) of their mandibular condyles. Qualitative radiographic evidence of temporomandibular joint disorders-osteoarthritis (TMJD-OA) assessment and quantitative microarchitecture analysis of their mandibular condylar bones were conducted. RESULTS: There was no statistically significant difference in either self-reported TMD or in radiographic evidence of TMJD-OA in PLWH compared with HIV-negative controls. Linear regression analysis revealed that positive HIV status remained significantly associated with increased trabecular thickness, decreased cortical porosity, and increased cortical bone volume fraction after adjusting for race, diabetes, sex, and age. CONCLUSION: PLWH have increased mandibular condylar trabecular bone thickness and cortical bone volume fraction compared with HIV-negative controls.

The inverse association between a fish consumption biomarker and gingival inflammation and periodontitis: A population-based study.

AIM: The metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) is a fatty fish-intake biomarker. We investigated the association between plasma levels of CMPF in relation to gingival inflammation and periodontitis case definition, as well as the extent and severity variables. MATERIALS AND METHODS: The Malmö Offspring Study is a population-based study, and the Malmö Offspring Dental Study (MODS) is its dental arm, including periodontal charting. Plasma CMPF was measured using liquid chromatography-mass spectrometry and studied in relation to periodontal diagnosis and parameters using multivariable linear or logistic regression modelling adjusting for age, sex, education, body mass index, fasting glucose, and smoking. RESULTS: Metabolite data were available for 922 MODS participants. Higher CMPF levels were associated with less gingival inflammation (ß = -2.12, p = .002) and lower odds of severe periodontitis (odds ratio [OR] = 0.74, 95% confidence interval [CI]: 0.56 to 0.98). Higher CMPF levels were also associated with more teeth (ß = 0.19, p = .001), lower number of periodontal pockets (≥4 mm) (ß = -1.07, p = .007), and lower odds of having two or more periodontal pockets of ≥6 mm (OR = 0.80, 95% CI: 0.65 to 0.98) in fully adjusted models. CONCLUSIONS: CMPF, a validated biomarker of fatty fish consumption, is associated with less periodontal inflammation and periodontitis. Residual confounding cannot be ruled out, and future studies are warranted.

The prospective association between periodontal disease and brain imaging outcomes: The Atherosclerosis Risk in Communities study.

AIM: We investigate if periodontal disease is prospectively associated with cerebrovascular and neurodegenerative markers of dementia and Alzheimer's pathology. MATERIALS AND METHODS: N = 1306 participants (Visit 5 mean age = 76.5 [standard deviation = 5.4] years) in the Atherosclerosis Risk in Communities study with completed dental exams at Visit 4 underwent brain magnetic resonance imaging scans at Visit 5 while N = 248 underwent positron emission tomography scans. Participants were classified as edentulous or, among the dentate, by the modified Periodontal Profile Class. Brain volumes were regressed on periodontal status in linear regressions. Cerebrovascular measures and ß-amyloid positivity were regressed on periodontal status in logistic regressions. RESULTS: Periodontal disease was not associated with brain volumes, microhaemorrhages, or elevated ß-amyloid. Compared with periodontally healthy individuals, odds ratios [95% confidence interval] for all-type infarcts were 0.37 [0.20, 0.65] for severe tooth loss and 0.56 [0.31, 0.99] for edentulous participants. CONCLUSIONS: Within the limitations of this study, periodontal disease was not associated with altered brain volumes, microhaemorrhages, or ß-amyloid positivity. Tooth loss was associated with lower odds of cerebral infarcts.

Diet quality and periodontal disease: Results from the oral infections, glucose intolerance and insulin resistance study (ORIGINS).

AIMS: This study examined the cross-sectional association between diet quality and periodontal disease. MATERIALS AND METHODS: In the Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS), 923 individuals completed the National Cancer Institute's validated Diet History Questionnaire 1, from which the Alternative Healthy Eating Index (AHEI) scores and A Priori Diet Quality Scores (APDQS) were calculated. Mean probing depth (MPD), mean clinical attachment loss (MAL) and % of sites bleeding on probing (%BOP) were derived from full-mouth periodontal exams. Multivariable adjusted linear and logistic regression models assessed the associations between diet quality and MPD, MAL, %BOP, and the odds of periodontitis (defined via the CDC/AAP classification). RESULTS: Alternative Healthy Eating Index and APDQS were not associated with MPD, MAL, or periodontitis. While AHEI was also not associated with %BOP, the APDQS was associated with %BOP (p = .03). Higher nut consumption was related to lower MPD (p = .03) and periodontitis odds (p = .03). Higher red meat consumption was associated with higher MPD (p = .01) and %BOP (p = .05). Higher trans-fatty acid consumption was also associated with increased %BOP (p = .05). CONCLUSION: Overall diet quality scores were not associated with periodontal status. Future studies are necessary to replicate the associations observed in this study to minimize the risk of false discovery.

The association between coeliac disease and periodontitis: Results from NHANES 2009-2012.

AIM: To investigate whether coeliac disease (CD) was associated with periodontitis among a nationally representative sample of US adults. MATERIALS AND METHODS: The National Health and Nutrition Examination Survey (NHANES) 2009-2012 enrolled 6,661 subjects with full-mouth periodontal examination and serological testing for antitissue transglutaminase (tTg) and antiendomysial (EMA) antibodies. CD was defined as (i) self-reported physician diagnosis while on a gluten-free diet; or (ii) tTg levels >10.0 U/ml and positive EMA results. Positive serology without self-reported diagnosis was defined as undiagnosed CD (UdxCD). Periodontitis was defined according to the CDC/AAP definition. Multivariable linear and logistic models were used to regress the mean probing depth (PD) or attachment loss (AL) outcomes across CD categories (none, diagnosed and undiagnosed). RESULTS: The prevalence of moderate/severe periodontitis and diagnosed/undiagnosed CD was 40% and 0.74%, respectively. Mean AL was lower among those with CD although results were not statistically significant (p = .67). The odds of periodontitis among individuals with diagnosed and undiagnosed CD were: 0.5(0.22, 1.16) and 0.62(0.1, 3.75), respectively. Mean PD levels among those without CD or with diagnosed or undiagnosed CD were 1.49 ± 0.02, 1.36 ± 0.11 and 1.31 ± 0.11 (p = .03). CONCLUSION: CD is associated with modestly lower levels of mean PD but was not associated with mean AL or periodontitis. Larger studies are necessary to enhance precision and strengthen conclusions.

The severity of human peri-implantitis lesions correlates with the level of submucosal microbial dysbiosis.

AIM: To cross-sectionally analyse the submucosal microbiome of peri-implantitis (PI) lesions at different severity levels. MATERIALS AND METHODS: Microbial signatures of 45 submucosal plaque samples from untreated PI lesions obtained from 30 non-smoking, systemically healthy subjects were assessed by 16s sequencing. Linear mixed models were used to identify taxa with differential abundance by probing depth, after correction for age, gender, and multiple samples per subject. Network analyses were performed to identify groups of taxa with mutual occurrence or exclusion. Subsequently, the effects of peri-implant probing depth on submucosal microbial dysbiosis were calculated using the microbial dysbiosis index. RESULTS: In total, we identified 337 different taxa in the submucosal microbiome of PI. Total abundance of 12 taxa correlated significantly with increasing probing depth; a significant relationship with lower probing depth was found for 16 taxa. Network analysis identified two mutually exclusive complexes associated with shallow pockets and deeper pockets, respectively. Deeper peri-implant pockets were associated with significantly increased dysbiosis. CONCLUSION: Increases in peri-implant pocket depth are associated with substantial changes in the submucosal microbiome and increasing levels of dysbiosis.

Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology.

BACKGROUND: Diabetes and periodontitis are chronic non-communicable diseases independently associated with mortality and have a bidirectional relationship. AIMS: To update the evidence for their epidemiological and mechanistic associations and re-examine the impact of effective periodontal therapy upon metabolic control (glycated haemoglobin, HbA1C). EPIDEMIOLOGY: There is strong evidence that people with periodontitis have elevated risk for dysglycaemia and insulin resistance. Cohort studies among people with diabetes demonstrate significantly higher HbA1C levels in patients with periodontitis (versus periodontally healthy patients), but there are insufficient data among people with type 1 diabetes. Periodontitis is also associated with an increased risk of incident type 2 diabetes. MECHANISMS: Mechanistic links between periodontitis and diabetes involve elevations in interleukin (IL)-1-ß, tumour necrosis factor-α, IL-6, receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio, oxidative stress and Toll-like receptor (TLR) 2/4 expression. INTERVENTIONS: Periodontal therapy is safe and effective in people with diabetes, and it is associated with reductions in HbA1C of 0.27-0.48% after 3 months, although studies involving longer-term follow-up are inconclusive. CONCLUSIONS: The European Federation of Periodontology (EFP) and the International Diabetes Federation (IDF) report consensus guidelines for physicians, oral healthcare professionals and patients to improve early diagnosis, prevention and comanagement of diabetes and periodontitis.

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.

Association between low-dose aspirin and periodontal disease: results from the continuous national health and nutrition examination survey (NHANES) 2011-2012.

AIM: Low-dose aspirin has been hypothesized as being a potential host modulatory agent for periodontitis treatment. We investigated the relationship between low-dose aspirin use and periodontitis prevalence in the continuous National Health and Nutrition Examination Survey, 2011-2012. METHODS: We analysed n = 2335 adult men and women who received a full-mouth periodontal examination and responded to an aspirin use questionnaire. Periodontal disease was defined as severe, moderate or mild according to established case definitions. Mean full-mouth probing depth, attachment loss and tooth loss were also considered. Low-dose aspirin was defined by any self-reported, physician prescribed aspirin use of ≤162 mg/day. RESULTS: Participants had mean age (SE) 55.8 years (0.42). The prevalences of periodontitis and low-dose aspirin use were 49.5% and 25% respectively. In multivariable logistic regression models controlling for age, sex, race, socioeconomic variables and comorbidities, the odds ratios [95%CI] for moderate or severe periodontitis among low-dose aspirin users (versus non-users) were: 0.91 [0.56-1.50] and 1.06 [0.74-1.50] respectively. Results were unchanged among participants without diabetes or coronary heart disease. CONCLUSIONS: Within the limitations of this cross-sectional study we conclude that low-dose aspirin is not associated with prevalent periodontal status in a nationally representative sample of US adults.

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.

Role of the NK cell-activating receptor CRACC in periodontitis.

Periodontitis is a highly prevalent, biofilm-mediated chronic inflammatory disease that results in the loss of the tooth-supporting tissues. It features two major clinical entities: chronic periodontitis, which is more common, and aggressive periodontitis, which usually has an early onset and a rapid progression. Natural killer (NK) cells are a distinct subgroup of lymphocytes that play a major role in the ability of the innate immune system to steer immune responses. NK cells are abundant in periodontitis lesions, and NK cell activation has been causally linked to periodontal tissue destruction. However, the exact mechanisms of their activation and their role in the pathophysiology of periodontitis are elusive. Here, we show that the predominant NK cell-activating molecule in periodontitis is CD2-like receptor activating cytotoxic cells (CRACC). We show that CRACC induction was significantly more pronounced in aggressive than chronic periodontitis and correlated positively with periodontal disease severity, subgingival levels of specific periodontal pathogens, and NK cell activation in vivo. We delineate how Aggregatibacter actinomycetemcomitans, an oral pathogen that is causally associated with aggressive periodontitis, indirectly induces CRACC on NK cells via activation of dendritic cells and subsequent interleukin 12 (IL-12) signaling. In contrast, we demonstrate that fimbriae from Porphyromonas gingivalis, a principal pathogen in chronic periodontitis, actively attenuate CRACC induction on NK cells. Our data suggest an involvement of CRACC-mediated NK cell activation in periodontal tissue destruction and point to a plausible distinction in the pathobiology of aggressive and chronic periodontitis that may help explain the accelerated tissue destruction in aggressive periodontitis.

Periodontal and Other Oral Bacteria and Risk of Lung Cancer in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Evidence suggests that periodontal disease is associated with increased lung cancer risk, but whether periodontal pathogens are explanatory is unknown. We prospectively studied associations of prediagnostic circulating antibodies with oral bacteria and of periodontal bacteria in subgingival plaque with lung cancer. METHODS: We included 4,263 cancer-free participants in the Atherosclerosis Risk in Communities study with previously measured serum IgG antibodies to 18 oral bacteria. In 1,287 participants for whom subgingival plaque was collected, counts for 8 periodontal bacteria were previously measured. Incident lung cancers (N = 118) were ascertained through 2015 (median follow-up = 17.5 years). We used Cox regression to estimate multivariable-adjusted associations, including for sums of antibodies to orange (C. rectus, F. nucleatum, P. intermedia, P. micra, and P. nigrescens) and red (P. gingivalis, T. forsythensis, and T. denticola) complex bacteria. RESULTS: Orange complex bacteria antibodies were positively associated with lung cancer [per IQR hazard ratios (HR) = 1.15; 95% confidence intervals (CI), 1.02-1.29], which was stronger in men (HR = 1.27, 95% CI 1.08-1.49), and explained by P. intermedia and P. nigrescens (HR = 1.15; 95% CI, 1.04-1.26). Suggestive positive associations with lung cancer (N = 40) were observed for F. nucleatum, A. actinomycetemcomitans, and P. gingivalis counts. Significant positive associations were found for the count to antibody ratio for P. intermedia and P. gingivalis. CONCLUSIONS: We identified positive associations with lung cancer for oral bacteria, especially orange complex that are moderately pathogenic for periodontal disease. IMPACT: This prospective study supports the need for more research on periodontal bacteria in lung cancer etiology. If associations are supported, this may inform novel lung cancer prevention strategies.

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.

Periodontal Status, C-Reactive Protein, NT-proBNP, and Incident Heart Failure: The ARIC Study.

BACKGROUND: Periodontal disease (PD), resulting from inflammatory host response to dysbiotic subgingival microbiota, has been linked to cardiovascular disease; however, its relationship to heart failure (HF) and its subtypes (heart failure with reduced ejection fraction [HFrEF] and heart failure with preserved ejection fraction [HFpEF]) is unexplored. OBJECTIVES: The authors hypothesize that the presence of PD is associated with increased risk of incident HF, HFpEF, and HFrEF. METHODS: A total of 6,707 participants (mean age 63 ± 6 years) of the ARIC (Atherosclerosis Risk In Communities) study with full-mouth periodontal examination at visit 4 (1996-1998) and longitudinal follow-up for any incident HF (visit 4 to 2018), or incident HFpEF and HFrEF (2005-2018) were included. Periodontal status was classified as follows: healthy, PD (as per Periodontal Profile Classification [PPC]), or edentulous. Multivariable-adjusted Cox proportional hazards models were used to calculate HRs and 95% CIs for the association between PPC levels and incident HF, HFpEF, or HFrEF. Additionally, biomarkers of inflammation (C-reactive protein [CRP]) and congestion (N-terminal brain natriuretic peptide [NT-proBNP]) were assessed. RESULTS: In total, 1,178 incident HF cases occurred (350 HFpEF, 319 HFrEF, and 509 HF of unknown type) over a median of 13 years. Of these cases, 59% had PD, whereas 18% were edentulous. PD was associated with an increased risk for HFpEF (HR: 1.35 [95% CI: 0.98-1.86]) and significantly increased risk for HFrEF (HR: 1.69 [95% CI: 1.18-2.43]), as was edentulism: HFpEF (HR: 2.00 [95% CI: 1.37-2.93]), HFrEF (HR: 2.19 [95% CI: 1.43-3.36]). Edentulism was associated with unfavorable change in CRP and NT-proBNP, whereas PD was associated only with CRP. CONCLUSIONS: Periodontal status was associated with incident HF, HFpEF, and HFrEF, as well as unfavorable changes in CRP and NT-proBNP.

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.

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.

Periodontal disease, tooth loss and incident rheumatoid arthritis: results from the First National Health and Nutrition Examination Survey and its epidemiological follow-up study.

AIMS: Infection may be a rheumatoid arthritis (RA) risk factor. We examined whether signs of periodontal infection were associated with RA development in the First National Health and Nutrition Examination Survey and its epidemiological follow-up study. MATERIAL AND METHODS: In 1971-1974, 9702 men and women aged 25-74 were enrolled and surveyed longitudinally (1982, 1986, 1987, 1992). Periodontal infection was defined by baseline tooth loss or clinical evidence of periodontal disease. Baseline (n = 138) and incident (n = 433) RA cases were defined via self-report physician diagnosis, joint pain/swelling, ICD-9 codes (714.0-714.9), death certificates and/or RA hospitalization. RESULTS: Adjusted odds ratios (ORs) (95% CI) for prevalent RA in gingivitis and periodontitis (versus healthy) were 1.09 (0.57, 2.10) and 1.85 (0.95, 3.63); incident RA ORs were 1.32 (0.85, 2.06) and 1.00 (0.68, 1.48). The ORs for prevalent RA among participants missing 5-8, 9-14, 15-31 or 32 teeth (versus 0-4 teeth) were 1.74 (1.03, 2.95), 1.82 (0.81, 4.10), 1.45 (0.62, 3.41) and 1.30 (0.48, 3.53); ORs for incident RA were 1.12 (0.77, 1.64), 1.67 (1.12, 2.48), 1.40 (0.85, 2.33) and 1.22 (0.75, 2.00). Dose-responsiveness was enhanced among never smokers. The rate of death or loss-to-follow-up after 1982 was two- to fourfold higher among participants with periodontitis or missing ≥9 teeth (versus healthy participants). CONCLUSIONS: Although participants with periodontal disease or ≥5 missing teeth experienced higher odds of prevalent/incident RA, most ORs were non-statistically significant and lacked dose-responsiveness. Differential RA ascertainment bias complicated the interpretation of these data.