Polymorphism of CD14 Gene Is Associated with Adverse Outcome among Patients Suffering from Cardiovascular Disease.

BACKGROUND: The biological link between severe periodontitis and cardiovascular disease is well established. Both complex inflammatory diseases are influenced by genetic background. Therefore, the impact of genetic variations of receptors of the innate immune system-(Toll-like receptors (TLRs)) TLR2, TLR4, cluster of differentiation 14 (CD14), and the transcription factor nuclear factor-κΒ (NF-κB)-was investigated. MATERIALS AND METHODS: In this study (ClinicalTrials.gov identifier: NCT01045070), 1002 cardiovascular (CV) patients were included. In a 3-year follow-up period, new vascular events were assessed. SNPs in CD14 (rs2569190), NF-κΒ (rs28362491), TLR2 (rs5743708), and TLR4 (rs4986790) were genotyped. The impact of these genetic variants on severe periodontitis as well as on CV outcome was assessed. RESULTS: All investigated genetic variants were not associated with preexisting CV events or severe periodontitis in CV patients. In Kaplan-Meier survival analyses, the CT genotype of CD14 single-nucleotide polymorphism (SNP) rs2569190 was shown to be an independent predictor for combined CV endpoint (log rank: p = 0.035; cox regression; hazard ratio: 1.572; p = 0.044) as well as cardiovascular death (log rank: p = 0.019; cox regression; hazard ratio: 1.585; p = 0.040) after three years of follow-up. CONCLUSIONS: SNPs in CD14, NF-κΒ, TLR2, and TLR4 are no risk modulators for preexisting CV events or severe periodontitis in CV patients. The CT genotype of CD14 SNP rs2569190 provides prognostic value for further CV events within 3 years of follow-up.

rs2476601 in PTPN22 gene in rheumatoid arthritis and periodontitis-a possible interface?

BACKGROUND: Rheumatoid arthritis (RA) and periodontitis (PD) are proven to share common risk markers, including genetic factors. In the present study we focused on genetic variants in PTPN22 (rs2476601), PADI4 (rs2240340), CTLA4 genes (rs3087243) and its impact on RA and PD. MATERIALS AND METHODS: In the study 111 RA patients and 256 systemically healthy controls were involved. A subdivision of patients and controls was carried out according the severity of periodontitis (no/level 1 PD vs. level 2 PD). RESULTS: I. Evaluating the genetic impact on the occurrence of RA the T allele of rs2476601 (PTPN22) (bivariate: p < 0.001; multivariate: p = 0.018) and T allele of rs2240340 (PADI4) (bivariate: p = 0.006; multivariate: p = 0.070) were associated with an increased vulnerability to RA. II. Investigating the genetic influence on level 2 PD the T allele of rs2476601 (PTPN22) was shown to be associated with a higher susceptibility to PD within the RA group (bivariate: p = 0.043; multivariate: p = 0.024). III. The T allele of rs2476601 (PTPN22) was proven to be a significant marker of RA and level 2 PD comorbidity (bivariate: p < 0.001; multivariate: p = 0.028). CONCLUSIONS: These results support the thesis that genetic variations may represent a possible link between PD and RA. The study increases knowledge about disease-specific and cross-disease genetic pattern.

ANRIL polymorphisms (rs1333049 and rs3217992) in relation to plasma CRP levels among in-patients with CHD.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in long non-coding RNA ANRIL (antisense noncoding RNA in the INK4 locus) were shown to be associated with coronary heart disease (CHD). The biological background for this association is not fully understood. The primary aim of this study was to investigate whether two leading ANRIL SNPs, namely, rs133049 and rs3217992, were associated with plasma levels of C-reactive protein among a large cohort of in-patients with CHD (n = 933). MATERIAL AND METHODS: CHD was defined as previous or current detection of 50% stenosis of a main coronary artery. Severe periodontitis was diagnosed if proximal attachment loss of at least 5 mm was found in at least 30% of teeth. For genotyping rs1333049 we applied PCR using sequence-specific primers and for rs321799 restriction fragment length polymorphism analyses. C-reactive protein (CRP) plasma levels were determined using a particle-enhanced immunological turbidity test. In addition, interleukin (IL)-6, low-density lipoprotein (LDL), total cholesterol, high-density lipoprotein (HDL), triglycerides, and number of leukocytes were determined. RESULTS: Genotype CC of rs1333049 was significantly associated with both elevated CRP levels and decreased HDL concentrations after univariate (p = 0.028, p = 0.012) and multivariate analysis (p = 0.041, p = 0.023) stratified for age, gender, body mass index, smoking, diabetes, and severe periodontitis. Furthermore, severe periodontitis (p = 0.031), but not SNP rs3217992, was associated with CRP plasma concentrations. CONCLUSIONS: Among patients with CHD, ANRIL SNP rs1333049 is an independent risk indicator for both elevated CRP plasma levels and reduced HDL concentrations. ClinicalTrials.gov Identifier: NCT01045070.

Is periodontitis a prognostic factor in order to indicate antibodies against citrullinated peptides in patients with rheumatoid arthritis?

OBJECTIVES: In this cross-sectional study we investigated antibody titres against cyclic citrullinated peptides derived from filaggrin (anti-CCP) and citrullinated α-enolase (anti-CEP-1) among patients with RA as a function of periodontal findings. METHODS: 107 patients with RA (median age 56 years, 75% females) were included. For periodontal diagnoses missing teeth, periodontal epithelial surface area, periodontal inflamed surface area and periodontal diagnosis according to the working group's guidelines of the Center for Disease Control and Prevention were determined. Subgingival bacterial DNA of five periodontopathic bacteria was assessed by PCR with sequence-specific oligonucleotides. Anti-CCP and anti-CEP-1 antibodies in plasma samples were investigated using enzyme-linked immunosorbent assays. Low resolution human leukocyte antigen (HLA) typing was carried out using PCR with sequence-specific primers. RESULTS: PESA was found associated with a low adjusted odds ratio for anti-CCP positivity (OR=1.002, p=0.040). All patients who were infected with Aggregatibacter actinomycetemcomitans were simultaneously anti-CCP positive (p=0.043). HLA-DRB1*13 lowered the adjusted odds ratio for anti-CCP (OR=0.073, p=0.002) and anti-CEP-1 (OR=0.068, p=0.018) positivity whereas HLA-DRB1*07 indicated a lower risk only for demonstrable anti-CCP antibodies (OR=0.079, p=0.004). HLA-DRB1*04 was associated with increased adjusted odds ratio for anti-CEP-1 positivity (OR=4.154, p=0.005) and the simultaneous proof of both investigated autoantibodies (OR=3.725, p=0.011). CONCLUSIONS: Among patients with RA periodontitis may be a minor risk factor for anti-CCP positivity. Our data first provide evidence that an infection with A. actinomycetemcomitans is associated with an increased formation of anti-CCP. HLA phenotype proved to be a significant risk indicator for both investigated antibodies.

Periodontal pathogens and their role in cardiovascular outcome.

AIM: Periodontitis has been identified as a moderate but independent risk factor for cardiovascular (CV) disease and progression. The objective of this study (ClinicalTrials.gov Identifier: NCT01045070) was to assess subgingival colonization with selected periodontal pathogens on the occurrence of further adverse CV events in a cohort of CV patients. METHODS: The prevalence of severe periodontitis including the detection of 11 periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Treponema denticola, P. intermdia, Peptostreptococcus micros, Fusobacterium nucleatum, Campylobacter rectus, Eubacterium nodatum, Eikenella corrodens, Capnocytophaga sputigena, Capnocytophaga gingivalis, Capnocytophaga ochracea; HAIN-Diagnostica® ) was analysed in 1,002 CV patients The prognostic impact of periodontal pathogens for combined CV endpoint (stroke/TIA, myocardial infarction, CV death, death from stroke) was evaluated after a 3-year follow-up period. Hazard ratios (HRs) were adjusted for established CV risk factors applying Cox regression. RESULTS: In the Kaplan-Meier analysis (log-rank test: p < .001) and Cox regression (HR: 0.545, 95%-CI: 0.387-0.773; p = .001), the decreased occurrence of E. corrodens was shown to be an independent predictor for adverse CV events after 3 years of follow-up. CONCLUSIONS: The detection of E. corrodens was associated with a reduced risk of adverse CV events in patients with CV disease. The pathophysiological background underlying this association should be investigated in further studies.

Are There Any Common Genetic Risk Markers for Rheumatoid Arthritis and Periodontal Diseases? A Case-Control Study.

BACKGROUND: Several studies suggest that there is a biologically plausible connection between rheumatoid arthritis (RA) and periodontal diseases (PD). Both disorders are characterized as multifactorial diseases potentially sharing common risk factors. Based on the inflammatory nature of RA and PD, the impact of genetic variations of genes of the immune system on both diseases was studied in this study. MATERIALS AND METHODS: We conducted a case-control study (n = 201) comparing 101 RA patients suffering from periodontal disease of different severities (no/mild PD vs. severe PD) with 100 systemically healthy controls without RA and severe PD. The genotype, allele, and haplotype distributions of 22 SNPs of 13 pro- and anti-inflammatory cytokines were assessed applying sequence-specific PCR. RESULTS: Evaluating the impact of cytokine SNPs in RA, we identified the G allele of rs1801275 in IL4Rα (p = 0.043) and the G allele of rs361525 in TNFα (p = 0.005) as disease-associated risk factors in bivariate analyses. In multivariate analyses, these significant associations could not be proven. The A allele of rs2430561 in IFNγ was indicative for severe periodontitis among the patients with rheumatoid arthritis (p = 0.039). Investigating the impact of rs2430561 in IFNγ on comorbidity using binary logistic regression analyses, the A allele was confirmed as an independent risk factor for severe periodontal disease and RA (p = 0.024). CONCLUSIONS: These results emphasize the association of genetic variations in proinflammatory cytokines (TNFα and IFNγ) and cytokine receptor (IL4Rα) and RA and periodontal diseases. In multivariate analyses, the A allele of IFNγ was proven to be a significant marker of RA and PD comorbidities. The study broadens the knowledge about disease-specific differences in genetic composition and provides an improved understanding of a possible association of both diseases.

Efficacy of desensitizing products containing 8% arginine and calcium carbonate for hypersensitivity relief in MIH-affected molars: an 8-week clinical study.

OBJECTIVES: The objective of this study was to compare the efficacy in reducing hypersensitivity in molar incisor hypomineralization (MIH)-affected molars immediately and over 8 weeks combining a single in-office application and a homed-based program with desensitizing products containing 8% arginine and calcium carbonate. MATERIALS AND METHODS: Nineteen children with at least one MIH-affected molar with hypersensitivity were included. Hypersensitivity was assessed with an evaporative (air) stimulus and a tactile stimulus. Each child received a single in-office treatment with a desensitizing paste containing 8% arginine and calcium carbonate (elmex Sensitive Professional desensitizing paste), followed by 8 weeks of brushing twice daily with a desensitizing toothpaste containing 8% arginine, calcium carbonate with 1450 ppm fluoride (elmex Sensitive Professional toothpaste), using the elmex Sensitive Professional toothbrush. Additionally, the corresponding mouthwash (elmex Sensitive Professional mouthwash) was used. Clinical assessments were made at baseline, immediately after the in-office treatment and after 1, 2, 4 and 8 weeks of brushing twice daily. RESULTS: Fifty-six molars with an air blast hypersensitivity score of 2 or 3 (Schiff Cold Air Sensitivity Scale) were included. Application of the desensitizing paste decreased hypersensitivity significantly immediately and throughout the 8 weeks recalls (p < 0.001). CONCLUSIONS: In conclusion, 8% arginine and calcium carbonate were able to reduce hypersensitivity successfully during this 8-week trial. CLINICAL RELEVANCE: Hypersensitivity is a major complaint in patients with MIH. This is the first study evaluating the desensitizing effect of a desensitizing paste containing 8% arginine and calcium carbonate in patients with MIH.

The interleukin 6 c.-174 CC genotype is a predictor for new cardiovascular events in patients with coronary heart disease within three years follow-up.

The main aim of this study was to evaluate putative associations between the interleukin (IL)-6 c.-174G>C polymorphism (rs 1800795) and the cardiovascular outcome (combined endpoint: myocardial infarction, stroke/TIA, cardiac death, death according to stroke) among patients with coronary heart disease (CHD) within three years follow-up. Overall 942 in-patients with CHD were included. The drop-out rate was 4.9%. The IL-6 polymorphism was determined with PCR-SSP. Kaplan-Meier plots with Log Rank test and Cox regression were used as statistically procedures. The IL-6 CC genotype was associated with a higher incidence of the combined endpoint (25.0% versus 13.5%, p<0.001) and an increased Hazard Ratio (HR 2.165, 95% CI 1.516-3.092, p<0.001) adjusted for established cofactors for CHD. This result suggests that the IL-6 -174 polymorphism is a putative independent risk indicator for new cardiovascular events among patients with CHD.

C-reactive protein levels and genetic variants of CRP as prognostic markers for combined cardiovascular endpoint (cardiovascular death, death from stroke, myocardial infarction, and stroke/TIA).

BACKGROUND: The aim of this analysis was to evaluate the importance of C-reactive protein levels and genetic variants of CRP as prognostic markers for further cardiovascular (CV) events (3-year follow-up) in a cohort of in-patients with cardiovascular disease (CVD) patients. METHODS AND RESULTS: Patients with angiographic proven CVD (n=939) were prospectively included. The three-year CV outcome of the patients was evaluated considering the predefined, combined endpoint (CV death, death from stroke, myocardial infarction, and stroke/TIA). Polymorphisms rs1800947, rs1417938, rs1130864, rs3093077 were analysed. In Kaplan-Meier survival curve and Cox regression increased CRP levels of ⩾5mg/l (log-rank test: p=0.001, Cox regression: hazard ratio=1.77, 95% CI: 1.2-2.7) and the GG genotype of rs1800947 (log-rank test: p=0.01, Cox regression: hazard ratio=1.99, 95% CI: 1.1-3.6) were associated with the incidence of the combined endpoint. CONCLUSIONS: Both a CRP level ⩾5mg/l and SNP rs1800947 of the CRP gene were independent risk factors for further adverse CV events among patients with CVD within three years follow-up.

Periodontal conditions and incidence of new cardiovascular events among patients with coronary vascular disease.

AIM: We wanted to investigate whether periodontal conditions and/or oral care habits are associated with new cardiovascular events among patients with coronary vascular disease (CVD). MATERIALS AND METHODS: In this longitudinal cohort study, 1002 inpatients with CVD were included. They were examined regarding prevalence of severe periodontitis, bleeding upon probing (BOP), number of missing teeth and oral care habits. The combined endpoint was defined as myocardial infarction, stroke/transient ischaemic attack, cardiovascular death and death caused by stroke. Survival analyses were carried out after a 3-year follow-up period. Hazard ratios (HRs) were adjusted for known cardiac risk factors using Cox regression. RESULTS: Nine hundred and fifty-three patients completed the 3-year follow-up. The overall incidence of the combined endpoint was 16.4%. Significant HRs for BOP (HR = 2, 95% CI: 1.2-3.3), severe tooth loss (HR = 1.8, 95% CI: 1.3-2.5), brushing teeth more than once a day (HR = 0.6, 95% CI: 0.5-1.0) and use of floss/inter-dental brushes (HR = 0.5, 95% CI: 0.3-0.9) were evaluated only in univariate but not in multivariate survival analyses. Patients with severe periodontitis achieved the combined endpoint more often (18.9% versus 14.2%), but the result was not statistically significant after both univariate and multivariate survival analyses. CONCLUSIONS: Periodontal conditions and oral care habits are not independent indicators for further adverse events in patients with CVD.

Association of levels of antibodies against citrullinated cyclic peptides and citrullinated α-enolase in chronic and aggressive periodontitis as a risk factor of Rheumatoid arthritis: a case control study.

BACKGROUND: Periodontal disease could be a risk factor for rheumatoid arthritis (RA). It is assumed that the bacterial strain Porphyromonas gingivalis mediates citrullination of host peptides and thereby the generation of RA-associated autoantibodies in genetically predisposed individuals. For that reason non-RA individuals who suffered from generalized aggressive (GAgP, N = 51) and generalized chronic periodontitis (GChP, N = 50) were investigated regarding the occurrence of antibodies against citrullinated cyclic peptides (anti-CCP) and citrullinated α-enolase peptide-1 (anti-CEP-1) in comparison to non-RA non-periodontitis controls (N = 89). Furthermore, putative associations between infections with five periodontopathic bacteria or expression of certain human leucocyte antigens (HLA) to these autoantibodies were investigated. METHODS: The presence of anti-CCP and anti-CEP-1 in plasma samples was conducted with enzyme linked immunosorbent assay. Subgingival plaque specimens were taken from the deepest pocket of each quadrant and pooled. For detection of DNA of five periodontopathic bacteria PCR with sequence specific oligonucleotides was carried out. Low resolution HLA typing was carried out with PCR with sequence specific primers. Differences between patients and controls were assessed using Chi square test with Yates correction or Fisher`s exact test if the expected number n in one group was <5. RESULTS: Two patients with GAgP (3.9%), no patient with GChP and two controls (2.2%, pFisher = 0.662) were positive for anti-CEP-1 whereas no study participant was anti-CCP positive. Individuals with P. gingivalis were slightly more often anti-CEP-1 positive in comparison to individuals without P. gingivalis (3.2 vs. 1.1%, pFisher = 0.366). Carrier of HLA-DQB1*06 or the HLA combination DRB1*13; DRB3*; DQB1*06 were slightly more anti-CEP-1 positive (6.1 and 4.3%) than no carriers (0.7 and 0%, pFisher 0.053). CONCLUSIONS: GAgP and GChP and the presence of periodontopathic bacteria are not associated with an increased risk for occurrence of anti-CCP and anti-CEP-1 autoantibodies. The putative relationship between periodontitis and RA should be investigated in further studies.

The importance of genetic variants in TNFα for periodontal disease in a cohort of coronary patients.

AIM: The aim of this analysis was to evaluate the importance of genetic variants of TNFα for the severity of periodontal disease and periodontal risk factors with respect to periodontal risk factors in a cohort of coronary patients. SUBJECTS: A total of 942 consecutive patients with angiographic proven coronary heart disease were prospectively included in the study entitled "Periodontitis and Its Microbiological Agents as Prognostic Factors in Patients With Coronary Heart Disease" (ClinicalTrials.gov identifier:NCT01045070). METHODS: After including of patients, an extensive periodontal examination also involving PCR-sampling for 11 periodontal bacteria was performed. In this subanalysis, single nucleotide polymorphisms (SNPs) c.-308G>A, c.-238G>A and haplotypes for TNFα were analysed by CTS-PCR-SSP Tray kit (Heidelberg, Germany). RESULTS: The AG+AA genotype of SNP c.-238G>A of TNFα gene was associated with the amount of clinical attachment loss in patients with coronary heart disease in multivariate regression analysis. Moreover, Prevotella intermedia occurred more frequently in carriers who were positive for the AG+AA genotype and A-allele of SNP c.-308G>A in bivariate and multivariate analyses. Furthermore, only in bivariate analyses significant associations of genetic variants of TNFα with intensified bleeding on probing and with higher plasma level of interleukin 6 could be shown. CONCLUSIONS: Genetic variants of TNFα gene, namely c.-308G>A and c.-238G>A, are associated with periodontal conditions in patients with coronary heart disease.

A prospective, randomized clinical trial of a two-step self-etching vs two-step etch-and-rinse adhesive and SEM margin analysis: four-year results.

PURPOSE: The aim of this blinded, randomized, prospective long-term study was to evaluate the clinical performance of the two-step self-etching adhesive AdheSE (AS, Ivoclar Vivadent) compared to the etch-and-rinse adhesive system Excite (EX, Ivoclar Vivadent) in combination with the hybrid resin composite Tetric Ceram HB (Ivoclar Vivadent) for Class I and II restorations. MATERIALS AND METHODS: In accordance with a split mouth design, 50 patients received 100 restorations in premolars and molars. The restorations were assigned at random to the self-etching (AS) or the etch-and-rinse (EX) group. Each restoration was scored according to the modified Ryge criteria at baseline and after 6, 12, 24 and 48 months. Epoxy resin replicas of 60 restorations were made at each observation period for an additional SEM analysis of the occlusal margins. RESULTS: After 4 years, 60 of 100 restorations could be evaluated. The cumulative survival rate for group EX was 100% and for group AS 96.7%. One restoration in group AS had failed due to marginal gap formation. For the criterion marginal adaption in group AS, significantly more bravo ratings (30%) were observed after 4 years compared to group EX (6.7%) (p < 0.05; Mann-Whitney U-test). The results of the SEM margin analysis revealed no significant differences between groups AS and EX (Mann-Whitney U-test; p > 0.05). CONCLUSION: Both adhesive systems performed satisfactorily over the four-year observation period. A significant deterioration over time was found for the criterion marginal adaption in AdheSE.

The German version of the Child Perceptions Questionnaire (CPQ-G11-14): translation process, reliability, and validity in the general population.

The aims of this study were to develop a German version of the Child Perceptions Questionnaire (CPQ11-14, a measure of oral health-related quality of life in 11-14-year-old children) and to assess the instrument's reliability and validity in German children ages 11-14. The English original version of the CPQ11-14 questionnaire was translated into German (CPQ-G11-14) by a forward-backward translation method. Reliability was investigated in 1,061 subjects aged 11-14 years from a regional sample (Wernigerode, Saxonia-Anhalt, Germany) who were recruited during the annual dental public health examination. The subjects completed the CPQ-G11-14 and were clinically examined for the presence of dental caries, plaque accumulation, and malocclusion. In the reliability assessment, questionnaire summary score test-retest reliability was excellent (intraclass correlation coefficient, 95% confidence interval (CI) = 0.83, 0.73-0.94) and internal consistency was satisfactory (Cronbach's alpha, lower limit of CI = 0.87, 0.86). Validity of the CPQ-G11-14 questionnaire was supported by correlations with global ratings of oral health and overall well-being that were moderate in magnitude and met expectations (r = 0.35; 95% CI, 0.30-0.40 and r = 0.30; 95% CI, 0.24-0.35, respectively). In conclusion, the German version of the CPQ11-14 was reliable and valid in a general population of 11-14-year-old German children.

Regional Disparities in Caries Experience and Associating Factors of Ghanaian Children Aged 3 to 13 Years in Urban Accra and Rural Kpando.

(1) The objective of this socio-epidemiologic cross-sectional study was to investigate caries burdens in Ghanaian children aged 3 to 13 years. The main focus was the analysis of urban-rural disparities and associating socio-demographic and behavioural factors. (2) Standardized caries examination with documentation of decayed, missing, filled deciduous (dmft) and permanent teeth (DMFT) was conducted in 11 school facilities according to WHO guidelines. A parental questionnaire gathered data considering associating factors. Descriptive statistics were used to evaluate their influence on caries prevalence and experience using mean dmft+DMFT, Significant Caries Index (SiC), and Specific Affected Caries Index (SaC). (3) In total, 313 study participants were included (mean age 7.7 ± 3.8 years; 156 urban, 157 rural). The urban region showed slightly higher caries prevalence (40.4% vs. 38.9%). The rural region had higher caries experience in mean dmft+DMFT (1.22 ± 2.26 vs. 0.96 ± 1.58), SiC (3.52 ± 2.73 vs. 2.65 ± 1.71), and SaC (3.15 ± 2.68 vs. 2.37 ± 1.68). Lower education and occupation level of parents and rural residence were associated to higher caries values. Sugary diet showed an inverse relation with caries prevalence and oral hygiene practices supported the generally known etiologic correlation. (4) This study highlights the importance of targeting children vulnerable to caries due to social inequality with adequate preventive means. The implementation of regular dental screening and education, e.g. in schools, may be helpful.

Campylobacter Species of the Oral Microbiota as Prognostic Factor for Cardiovascular Outcome after Coronary Artery Bypass Grafting Surgery.

BACKGROUND: The oral microbiota has been implicated in a variety of systemic diseases, including cardiovascular (CV) disease. The main objective of this study (DRKS-ID: DRKS00015776) was to evaluate the prognostic importance of the oral microbiota for further CV events in patients undergoing coronary artery bypass grafting surgery (3-year follow-up). METHODS: In this longitudinal cohort study, 102 CV patients were enrolled, of whom 95 completed the 3-year follow-up. The CV outcome was assessed using the major adverse cardiac and cerebrovascular events criteria. To evaluate subgingival colonization, 16S rRNA genes were amplified, targeting the V3/V4 region (Illumina MiSeq). RESULTS: Regarding the specific number of operational taxonomic units (OTUs), no significant differences in CV outcome were determined (alpha diversity, Shannon index). In linear discriminant analyses and t-tests, the disease-specific differences in the beta diversity of the microbiota composition were evaluated. It was evident that bacteria species of the genus Campylobacter were significantly more prevalent in patients with a secondary CV event (p = 0.015). This hierarchical order also includes Campylobacter rectus, which is considered to be of comprehensive importance in both periodontal and CV diseases. CONCLUSIONS: Here, we proved that subgingival occurrence of Campylobacter species has prognostic relevance for cardiovascular outcomes in CV patients undergoing coronary artery bypass grafting.

Advanced Glycation End Product (AGE) and Soluble Receptor of AGE (sRAGE) Levels in Relation to Periodontitis Severity and as Putative 3-Year Outcome Predictors in Patients Undergoing Coronary Artery Bypass Grafting (CABG).

Tissue concentrations of advanced glycation end product (AGE) and peripheral soluble receptor of AGE (sRAGE) levels may be associated with periodontitis severity. Both parameters and periodontitis might serve as outcome predictors for patients undergoing coronary artery bypass grafting (CABG). This study aimed to investigate possible associations between periodontitis and AGE/sRAGE. Ultimately, we wanted to examine whether AGE, sRAGE, and severe periodontitis are associated with the incidence of new cardiovascular events within 3 years of follow-up after CABG. Ninety-five patients with coronary vascular disease (CVD) (age 69 years, 88.3% males) needing CABG surgery were included. Periodontal diagnosis was made according to the guidelines of the "Centers for Disease Control and Prevention (CDC)" (2007) and staged according to the new classification of periodontal diseases (2018). AGE tissue concentrations were assessed as skin autofluorescence (sAF). sRAGE levels were determined by using a commercially available enzyme-linked immunoabsorbance assay (ELISA) kit. Univariate and multivariate baseline and survival analyses were carried out with Mann-Whitney U test, Chi² test, Kaplan-Meier curves with Log-Rank test, and logistic and Cox regression. sAF was identified as an independent risk indicator for severe periodontitis with respect to the cofactors age, gender, plaque index, and diabetes (adjusted odds ratio [OR] = 2.9, p = 0.028). The degree of subgingival inflammation assessed as a percentage of sites with bleeding on probing (BOP) was inversely correlated with sRAGE concentration (r = -0.189, p = 0.034). Both sAF (Hazard Ratio [HR] = 2.4, p = 0.004) and sRAGE (HR = 1.9, p = 0.031) increased the crude risk for new adverse events after CABG. The occurrence of severe periodontitis trends towards a higher risk for new cardiovascular events (HR = 1.8, p = 0.115). Applying multivariate Cox regression, only peripheral arterial disease (adjusted HR = 2.7, p = 0.006) and history of myocardial infarction (adjusted HR = 2.8, p = 0.010) proved to be independent risk factors for cardiovascular outcome. We conclude that sAF may represent a new, independent risk indicator for severe periodontitis. In contrast, sAF, sRAGE, and severe periodontitis were not independent prognostic factors for postoperative outcome in patients undergoing CABG.

Nonsurgical Periodontal Treatment Options and Their Impact on Subgingival Microbiota.

BACKGROUND: Different periodontal treatment methods (quadrant-wise debridement, scaling and root planing (Q-SRP), full-mouth scaling (FMS), full-mouth disinfection (FMD), and FMD with adjuvant erythritol air-polishing (FMDAP)) were applied in periodontitis patients (stage III/IV). The study objective (substudy of ClinicalTrials.gov Identifier: NCT03509233) was to compare the impact of treatments on subgingival colonization. METHODS: Forty patients were randomized to the treatment groups. Periodontal parameters and subgingival colonization were evaluated at baseline and 3 and 6 months after treatment. RESULTS: Positive changes in clinical parameters were recorded in every treatment group during the 3-month follow-up period, but did not always continue. In three groups, specific bacteria decreased after 3 months; however, this was associated with a renewed increase after 6 months (FMS: Porphyromonas gingivalis; FMD: Eubacterium nodatum, Prevotella dentalis; and FMDAP: uncultured Prevotella sp.). CONCLUSIONS: The benefit of all clinical treatments measured after 3 months was associated with a decrease in pathogenic bacteria in the FMS, FMD, and FMDAP groups. However, after 6 months, we observed further improvement or some stagnation in clinical outcomes accompanied by deterioration of the microbiological profile. Investigating the subgingival microbiota might help appraise successful periodontal treatment and implement individualized therapy.

Is Periodontitis a Predictor for an Adverse Outcome in Patients Undergoing Coronary Artery Bypass Grafting? A Pilot Study.

Periodontitis is a risk factor for atherosclerosis and coronary vascular disease (CVD). This research evaluated the relationship between periodontal conditions and postoperative outcome in patients who underwent coronary artery bypass grafting (CABG). A total of 101 patients with CVD (age 69 years, 88.1% males) and the necessity of CABG surgery were included. Periodontal diagnosis was made according to the guidelines of the Centers for Disease Control and Prevention (CDC, 2007). Additionally, periodontal epithelial surface area (PESA) and periodontal inflamed surface area (PISA) were determined. Multivariate survival analyses were carried out after a one-year follow-up period with Cox regression. All study subjects suffered from periodontitis (28.7% moderate, 71.3% severe). During the follow-up period, 14 patients (13.9%) experienced a new cardiovascular event (11 with angina pectoris, 2 with cardiac decompensation, and 1 with cardiac death). Severe periodontitis was not significant associated with the incidence of new events (adjusted hazard ratio, HR = 2.6; p = 0.199). Other risk factors for new events were pre-existing peripheral arterial disease (adjusted HR = 4.8, p = 0.030) and a history of myocardial infarction (HR = 6.1, p = 0.002). Periodontitis was not found to be an independent risk factor for the incidence of new cardiovascular events after CABG surgery.

The role of Saccharibacteria (TM7) in the subginival microbiome as a predictor for secondary cardiovascular events.

BACKGROUND: The composition of the subgingival microbiota is of great importance in both oral and systemic diseases. However, a possible association of the oral microbiome and cardiovascular (CV) outcome has not yet been considered in a complex model. The primary objective of the study (DRKS-ID: DRKS00015776) was to assess differences in complex subgingival bacterial composition, depending on the CV outcome in patients undergoing Coronary Artery Bypass Grafting Surgery (CABG). MATERIAL AND METHODS: We conducted a longitudinal cohort study enrolling 102 CV patients. After a one-year follow-up, the postoperative outcome was evaluated applying MACCE (Major Adverse Cardiac and Cerebrovascular Events) criteria. The complex oral microbiome was evaluated depending on CV outcome. The mathematical data processing included Qiime 2 software workflow and DADA2 pipeline as well as Human Oral Microbiome Database (HOMD) and Greengenes database classification. For identifying biomarkers distinguishing patients suffering from secondary CV events, the Cox Proportional Hazard Model for survival analysis was applied. RESULTS: In total, 19,418 Operational Taxonomic Units (OTU) were mapped according to the HOMD and Greengenes database. No significant differences in alpha and beta diversity were linked to CV outcomes (Shannon index; Principal Coordinates Analysis). No biomarker predicting secondary CV events were identified applying the area under the receiver operating characteristic curve (AUC) model. However, in survival analysis, one biomarker of Saccharibacteria phylum (class: TM7-3, order: CW040, family: F16) was associated with the incidence of a secondary CV event (p = 0.016). CONCLUSIONS: For the first time, a subgingival biomarker has been identified that supports a cardiovascular prognosis in CV patients undergoing coronary artery bypass grafting.