Phoebus N. Madianos

Periodontal Disease and Coronary Heart Disease A Reappraisal of the Exposure

Background—Results from studies relating periodontal disease to cardiovascular disease have been mixed. Residual confounding by smoking and use of clinical measures of periodontal disease rather than measures of infection have been 2 major criticisms. The aims of this study were to investigate relationships between prevalent coronary heart disease (CHD) and 2 exposures, (1) clinical periodontal disease and (2) IgG antibodies to 17 oral organisms, and to evaluate the role of smoking in these relationships. Methods and Results—Our study is based on a subset of participants in the Atherosclerosis Risk in Communities (ARIC) Study, who received a complete periodontal examination during visit 4 (1996–1998). The exposures were periodontal status and serum IgG antibody levels against 17 periodontal organisms, and the outcome was prevalent CHD at visit 4. Multivariable analyses indicate that periodontal status is not significantly associated with CHD in either ever smokers or never smokers. Similar analyses evaluating antibodies indicate that high antibodies (above the median) to Treponema denticola (odds ratio [OR]=1.7; 95% CI, 1.2 to 2.3), Prevotella intermedia (OR=1.5; 95% CI, 1.1 to 2.0), Capnocytophaga ochracea (OR=1.5; 95% CI, 1.1 to 2.1), and Veillonella parvula (OR=1.7; 95% CI, 1.2 to 2.3) are significantly associated with CHD among ever smokers, whereas Prevotella nigrescens (OR=1.7; 95% CI, 1.1 to 2.6), Actinobacillus actinomycetemcomitans (OR=1.7; 95% CI, 1.2 to 2.7), and Capnocytophaga ochracea (OR=2.0; 95% CI, 1.3 to 3.0) were associated with CHD among never smokers. Conclusions—Clinical signs of periodontal disease were not associated with CHD, whereas systemic antibody response was associated with CHD in ever smokers and never smokers. These findings indicate that the quality and quantity of the host response to oral bacteria may be an exposure more relevant to systemic atherothrombotic coronary events than clinical measures.

Low-grade inflammation in chronic infectious diseases: paradigm of periodontal infections.

Abstract:  Increasing evidence implicates periodontitis, a chronic inflammatory disease of the tooth‐supporting structures, as a potential risk factor for increased morbidity or mortality for several systemic conditions including cardiovascular disease (atherosclerosis, heart attack, and stroke), pregnancy complications (spontaneous preterm birth [SPB]), and diabetes mellitus. Cross‐sectional, case–control, and cohort studies indicate that periodontitis may confer two‐ and up to sevenfold increase in the risk for cardiovascular disease and premature birth, respectively. Given the recently acquired knowledge that systemic inflammation may contribute in the pathogenesis of atherosclerosis and may predispose to premature birth, research in the field of periodontics has focused on the potential of this chronic low‐grade inflammatory condition to contribute to the generation of a systemic inflammatory phenotype. Consistent with this hypothesis clinical studies demonstrate that periodontitis patients have elevated markers of systemic inflammation, such as C‐reactive protein (CRP), interleukin 6 (IL‐6), haptoglobin, and fibrinogen. These are higher in periodontal patients with acute myocardial infarction (AMI) than in patients with AMI alone, supporting the notion that periodontal disease is an independent contributor to systemic inflammation. In the case of adverse pregnancy outcomes, studies on fetal cord blood from SBP babies indicate a strong in utero IgM antibody response specific to several oral periodontal pathogens, which induces an inflammatory response at the fetal–placental unit, leading to prematurity. The importance of periodontal infections to systemic health is further strengthened by pilot intervention trials indicating that periodontal therapy may improve surrogate cardiovascular outcomes, such as endothelial function, and may reduce four‐ to fivefold the incidence of premature birth. Nevertheless, further research is needed to fully discern the underlying mechanisms by which local chronic infections can have an impact on systemic health, and in this endeavor periodontal disease may serve as an ideal disease model.

Porphyromonas gingivalis Bacteremia Induces Coronary and Aortic Atherosclerosis in Normocholesterolemic and Hypercholesterolemic Pigs

Objectives—The aim of this study was to determine whether recurrent intravenous injections with Porphyromonas gingivalis (P gingivalis), mimicking periodontitis-associated bacteremia, promotes coronary artery and aortic atherosclerosis in pigs. Methods and Results—Pigs (n=36) fed low- or high-fat chow were divided into P gingivalis–sensitized and P gingivalis–challenged groups or P gingivalis–sensitized controls and saline-treated controls. Pigs were sensitized with 109 killed P gingivalis subcutaneously. Four weeks later all sensitized pigs in the group to be challenged started intravenous injections thrice weekly for 5 months with 106 to 107 colony forming units of P gingivalis while controls received saline. Anti–P gingivalis antibody, serum cholesterol, and complete blood counts were assayed monthly. Pigs were euthanized 2 weeks after the last injection, and coronary arteries and aortas were analyzed by histomorphometry and immunohistochemistry. Anti–P gingivalis antibody was increased by P gingivalis exposure. P gingivalis–challenged pigs developed a significantly greater amount of coronary and aortic atherosclerosis than controls in the normocholesterolemic group and nearly significant in the hypercholesterolemic group. P gingivalis was detected by polymerase chain reaction in arteries from most (94%, 16 of 17) P gingivalis–challenged pigs but not controls. Conclusions—Recurrent P gingivalis bacteremia induces aortic and coronary lesions consistent with atherosclerosis in normocholesterolemic pigs and increases aortic and coronary atherosclerosis in hypercholesterolemic pigs.

Cytokine Responses of Oral Epithelial Cells to Porphyromonas gingivalis Infection

Accumulating evidence indicates that epithelia are not merely mechanical barriers but also important elements of the innate immune system. The present study was performed to examine cytokine responses of oral epithelial cells after infection with the periodontal pathogen Porphyromonas gingivalis. The KB-cell line and primary cultures of periodontal pocket epithelium were infected with P. gingivalis for assessment of bacterial invasion by an antibiotic protection assay, and examinination of expression of interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha by in situ hybridization and immunohistochemistry. We observed that P. gingivalis induces a strong cytokine response, positively correlated with the adhesive/invasive potential of the infecting strain, in both KB cells and primary cultures. These findings indicate that the epithelial cells of the periodontal pocket are an integral part of the immune system, eliciting cytokine responses to a bacterial challenge. In this context, the adhesive/invasive phenotype of P. gingivalis appears to contribute to pathogenicity.

A randomized, controlled trial on the effect of non‐surgical periodontal therapy in patients with type 2 diabetes. Part I: effect on periodontal status and glycaemic control

AIM the purpose of the present study was to assess the effect of non-surgical periodontal therapy on glycaemic control of type 2 diabetes patients with moderate-to-severe periodontitis. MATERIALS AND METHODS this was a randomized, controlled clinical trial of patients with type 2 diabetes. A total of 60 patients with moderate-to-severe periodontal disease were assigned to either a periodontal treatment arm, consisting of scaling and root planing (intervention group [IG]), or a delayed treatment arm that received periodontal care after 6 months (control group [CG]). Periodontal parameters and glycosylated haemoglobin (A1C) were evaluated at 1, 3 and 6 months. RESULTS all periodontal parameters improved significantly in the IG. A1C levels decreased statistically significantly more in the IG versus the CG (0.72%versus 0.13%; p<0.01) independently of other confounders. CONCLUSIONS this study provides evidence that periodontal treatment contributes to improved glycaemic control in type 2 diabetes mellitus patients. Larger controlled trials are needed to confirm if this finding is generalizable to other populations of patients with type 2 diabetes.

Preterm low birth weight and periodontal disease among African Americans

African Americans consistently experience higher rates of preterm and low birth weight (LBW) deliveries than do whites. LBW and preterm infants are more likely to die before their first birthday and survivors may suffer from a number of health problems. Therefore, identification of modifiable risk factors for preterm deliveries and LBW has considerable public health significance. Pregnant womens poor periodontal healtlh is emerging as one such factor. Maternal clinical periodontal status and bacteriologic and immunologic profiles related to periodontal disease have been associateted with risk of fetal growth and preterm LBW, and periodontal treatment during pregnancy has reduced the incidence of preterm deliveries. This article reviews the literature on the above association and presents data from a previously published prospective study of predominantly African Americans to show that preterm LBW deliveries are associated with higher midtrimester maternal serum antibody levels against Porphyromonas gingivalis.

Effect of Non-Surgical Periodontal Therapy on C-Reactive Protein, Oxidative Stress, and Matrix Metalloproteinase (MMP)-9 and MMP-2 Levels in Patients With Type 2 Diabetes: A Randomized Controlled Study

BACKGROUND It is well accepted that glycemic control in patients with diabetes mellitus (DM) is affected by systemic inflammation and oxidative stress. The effect of periodontal therapy on these systemic factors may be related to improvement on glycemic status. The aim of the present study is to assess over a period of 6 months the effect of non-surgical periodontal therapy on serum levels of high-sensitivity C-reactive protein (hsCRP), d-8-iso prostaglandin F2a (d-8-iso) as a marker of oxidative stress, and matrix metalloproteinase (MMP)-2 and MMP-9 on patients with type 2 DM. METHODS Sixty participants with type 2 DM and moderate to severe periodontal disease were randomized into intervention (IG) and control (CG) groups. IG received scaling and root planing, whereas CG received supragingival cleaning at baseline and scaling and root planing at 6 months. Participants of both groups were evaluated at baseline and 1, 3, and 6 months. Periodontal data recorded at each visit included probing depth, clinical attachment loss, bleeding on probing, and gingival index. Blood was collected at each visit for the assay of serum glycated hemoglobin A1c (A1c), hsCRP, d-8-iso, MMP-2, and MMP-9. RESULTS Although there was a trend to a reduction in hsCRP, d-8-iso and MMP-9 it did not reach statistical significance. MMP-2 levels remained unchanged after periodontal treatment. CONCLUSION Effective non-surgical periodontal treatment of participants with type 2 DM and moderate to severe periodontal disease improved significantly A1c levels but did not result in a statistically significant improvement in hsCRP, d-8-iso, MMP-2, and MMP-9 levels.

Efficacy of periodontal plastic procedures in the treatment of multiple gingival recessions

OBJECTIVE To systematically review the efficacy of periodontal plastic procedures (PPP) in the treatment of multiple gingival recessions (MGR). METHODS Randomized clinical trials (RCT) on MGR treatment with at least 6 months duration were identified through electronic databases and hand-searched journals. Primary outcomes were complete root coverage (CRC) and percentage of root coverage (PRC). Weighted means and forest plots were calculated for all PPP. Subgroup analysis was performed according to the type of flap. A Bayesian network meta-analysis (NM) on secondary outcomes was also performed. RESULTS Nine trials including 208 subjects and 858 recessions were identified. CRC after PPP was 24-89%. Mean weighted PRC was 86.27% (95% CI 80.71-91.83; p < 0.01). Heterogeneity of the literature prevented inter-techniques comparison. Coronally advanced flap (CAF) shows the higher variability in terms of CRC. Modified CAF and tunnel approaches show higher level of CRC. The NM suggests that CAF plus graft showed the higher probability of being the best treatment. CONCLUSIONS Limited evidence is available for MGR coverage. PPP are associated with high level of efficacy, in terms of PRC, and high variability of CRC. Indirect evidence indicates that CAF may benefit from newer variations of the technique and by the additional use of grafting.

Comparison of Bacterial Community Composition of Primary and Persistent Endodontic Infections Using Pyrosequencing

INTRODUCTION Elucidating the microbial ecology of endodontic infections (EIs) is a necessary step in developing effective intracanal antimicrobials. The aim of the present study was to investigate the bacterial composition of symptomatic and asymptomatic primary and persistent infections in a Greek population using high-throughput sequencing methods. METHODS 16S amplicon pyrosequencing of 48 root canal bacterial samples was conducted, and sequencing data were analyzed using an oral microbiome-specific and a generic (Greengenes) database. Bacterial abundance and diversity were examined by EI type (primary or persistent), and statistical analysis was performed by using non-parametric and parametric tests accounting for clustered data. RESULTS Bacteroidetes was the most abundant phylum in both infection groups. Significant, albeit weak associations of bacterial diversity were found, as measured by UniFrac distances with infection type (analyses of similarity, R = 0.087, P = .005) and symptoms (analyses of similarity, R = 0.055, P = .047). Persistent infections were significantly enriched for Proteobacteria and Tenericutes compared with primary ones; at the genus level, significant differences were noted for 14 taxa, including increased enrichment of persistent infections for Lactobacillus, Streptococcus, and Sphingomonas. More but less abundant phyla were identified using the Greengenes database; among those, Cyanobacteria (0.018%) and Acidobacteria (0.007%) were significantly enriched among persistent infections. Persistent infections showed higher phylogenetic diversity (PD) (asymptomatic: PD = 9.2, standard error [SE] = 1.3; symptomatic: PD = 8.2, SE = 0.7) compared with primary infections (asymptomatic: PD = 5.9, SE = 0.8; symptomatic: PD = 7.4, SE = 1.0). CONCLUSIONS The present study revealed a high bacterial diversity of EI and suggests that persistent infections may have more diverse bacterial communities than primary infections.

Periodontal disease is associated with higher levels of C-reactive protein in non-diabetic, non-smoking acute myocardial infarction patients

OBJECTIVES A link between periodontal disease (PD) and cardiovascular events has been proposed, but confounding by shared risk factors such as smoking and diabetes remains a concern. We examined the prevalence of PD and its contribution to C-reactive protein (CRP) levels in acute myocardial infarction (AMI) patients and in subjects without AMI and with angiographically nonobstructive coronary disease in the absence of these confounding risk factors. METHODS Periodontal status and admission CRP levels were evaluated in 87 non-diabetic and non-smoking subjects undergoing cardiac catheterization. The study group comprised of 47 patients with documented AMI, and 40 subjects without AMI and with angiographically nonobstructive coronary disease (ANCD group). RESULTS Both the prevalence of PD and CRP levels were significantly higher in AMI patients compared with ANCD subjects (38.3% vs. 17.5%, p=0.03 and 44.3 vs. 8.5 mg/L, p<0.001 respectively). PD was associated with higher CRP levels in AMI patients (52.5 vs. 36.1 mg/L, p=0.04) as well as in ANCD subjects, however, in this group this was not significant (12.6 vs. 7.6 mg/L, p=0.5). Multivariable regression analysis confirmed two separate measures of PD as strong and independent contributors to elevated CRP levels in AMI patients (R2 = 0.28, R2 = 0.30, p=0.001). CONCLUSIONS PD contributes to elevated CRP levels in non-diabetic, non-smoking AMI patients, independently of other confounding factors. These findings imply that periodontitis may emerge as a novel target for reducing future risk in AMI survivors.