Periodontal infections and atherosclerotic vascular disease: an update

The role of periodontal infections as a putative risk factor for atherosclerotic vascular disease (ASVD) has been reported in the literature over the past decade. This review provides insights into biologically plausible pathways that can potentially mediate such an association, and discusses recent findings from epidemiological studies and intervention trials. Accumulating epidemiological evidence suggests that clinical, microbiological and serological markers of periodontal infection are associated with subclinical and manifest ASVD. Early evidence from intervention studies suggests that the control of periodontal infections may result in improved levels of markers of systemic inflammation and measures of endothelial dysfunction. The extent to which the control of periodontal infections results in lower incidence of ASVD events is logistically difficult to assess and has not been addressed in any study so far.     

Periodontitis and risk for atherosclerosis: an update on intervention trials

Aims: Periodontitis has been associated with an increased risk of cardiovascular events. The nature of the association is unclear because both periodontitis and cardiovascular disease (CVD) share a host of risk factors. Intervention trials are critical to explore the relationship. If the association were causal, successful periodontal therapy will lead to an attenuation of the effect – CVD.
Material and Methods: The paper reviewed the design and the results of intervention trials aimed at improving systemic inflammation, endothelial dysfunction, carotid atherosclerosis and cardiovascular events.
Results: Early systematic reviews and a definitive controlled clinical trial indicate that intensive periodontal therapy results in a decrease in systemic inflammation and an improvement of endothelial dysfunction in systemically healthy subjects. A pilot trial has indicated the feasibility to assess the impact of periodontal therapy on carotid atherosclerosis in a primary cardiac prevention design.
Conclusions: Efforts to test causality in the relationship between periodontitis and CVD are ongoing. Evidence to date is consistent with the notion that severe generalized periodontitis causes systemic inflammation and endothelial dysfunction. Periodontitis has effects that go beyond the oral cavity and its treatment and prevention may contribute to the prevention of atherosclerosis.     

The effect of initial treatment of periodontitis on systemic markers of inflammation and cardiovascular risk: a randomized controlled trial

Taylor B, Tofler G, Morel‐Kopp M‐C, Carey H, Carter T, Elliott M, Dailey C, Villata L, Ward C, Woodward M, Schenck K. The effect of initial treatment of periodontitis on systemic markers of inflammation and cardiovascular risk: a randomized controlled trial. Eur J Oral Sci 2010; 118: 350–356. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci Observational studies indicate that chronic periodontal disease is associated with adverse cardiovascular outcomes. The aim of this study was to determine whether initial periodontal treatment has a beneficial effect on systemic markers of inflammation and cardiovascular risk. One hundred and thirty‐six adults with chronic periodontitis were allocated to either intervention or control groups in a 3‐month randomized controlled intervention study. The intervention group received initial periodontal treatment, whereas the control group did not receive that treatment until after the study. Blood levels of cardiovascular risk factors, and of hematological, inflammatory, and metabolic markers, were measured at the beginning and the end of the study, and differences were calculated. Fibrinogen level was the primary outcome measure. Data for 61 persons in the intervention group and for 64 persons in the control group were available for statistical analysis. Compared with the control group, the intervention group showed a non‐significant trend for a lower fibrinogen level. Significant increases in hemoglobin and hematocrit were seen after treatment, showing that initial periodontal treatment, a relatively simple and cost‐effective intervention, has systemic effects.     

Radiation‐induced oral mucositis and periodontitis – proposal for an inter‐relationship

Virtually all patients who receive head and neck radiotherapy develop some degree of oral mucositis. Severe oral mucositis may necessitate an interruption of the course of radiotherapy and thus can serve as a dose‐limiting factor. Periodontitis is a host‐driven inflammatory response to a pathogenic bacterial biofilm in the subgingival environment, resulting in the progressive destruction of the tissues that support the teeth, specifically the gingiva, periodontal ligament and alveolar bone. This disease affects more than 50% of the population. Considering that radiation‐induced oral mucositis and periodontitis are both linked with continuing presence of systemic inflammation, they may be associated through a primed inflammatory response as proposed by the ‘two‐hit’ model. Alternatively, both conditions may be correlated as they represent a dysregulation of the inflammatory response. To date, no studies have looked into the association between these conditions. This review considers the current evidence that provides a rationale for proposing a link between periodontitis and oral mucositis.     

Novel endothelial biomarkers: implications for periodontal disease and CVD

Endothelial cells are actively involved in various aspects of vascular biology and different stages of atherosclerosis. Endothelial function is increasingly used as an important outcome measure in cardiovascular research. Endothelial progenitor cells (EPCs) are closely linked to endothelial function, and their biomarkers have received much attention. EPCs may not only serve as a pool of progenitor cells and possess the capacity to repair the damaged vasculature, but also act as potent effectors in systemic inflammation, suggesting that EPCs may play a critical role in maintaining endothelial function and the progression of cardiovascular disease (CVD). Emerging evidence shows an association of periodontal infections (gingivitis and periodontitis) with endothelial dysfunction, while the relevant mechanisms remain unknown. Our recent finding of the association of periodontitis with EPCs warrants their utilization as additional biomarkers in future studies on periodontal medicine. This review starts with a brief account on the current understanding of the nature of periodontal infections and their link with systemic inflammation and endothelial dysfunction. The paper also provides an update on endothelial biology and function as well as the novel biomarkers of EPCs and concludes with clinical studies on periodontal diseases and CVD.     

Role of high endothelial postcapillary venules and selected adhesion molecules in periodontal diseases: a review

Periodontitis is accompanied by the proliferation of small blood vessels in the gingival lamina propria. Specialized postcapillary venules, termed periodontal high endothelial‐like venules, are also present, and demonstrate morphological and functional traits similar to those of high endothelial venules (HEVs) in lymphatic organs. The suggested role of HEVs in the pathogenesis of chronic periodontitis involves participation in leukocyte transendothelial migration and therefore proinflammatory effects appear. Recent observations suggest that chronic periodontitis is an independent risk factor for systemic vascular disease and may result in stimulation of the synthesis of acute phase protein by cytokines released by periodontal high endothelial cells (HECs). However, tissue expression of HEV‐linked adhesion molecules has not been evaluated in the gingiva of patients with chronic periodontitis. This is significant in relation to potential therapy targeting expression of the adhesion molecules. In this review, current knowledge of HEV structure and the related expression of four surface adhesion molecules of HECs [CD34, platelet endothelial cell adhesion molecule 1, endoglin and intercellular adhesion molecule 1 (ICAM‐1)], involved in the key steps of the adhesion cascade in periodontal diseases, are discussed. Most studies on the expression of adhesion molecules in the development and progression of periodontal diseases pertain to ICAM‐1 (CD54). Studies by the authors demonstrated quantitatively similar expression of three of four selected surface markers in gingival HEVs of patients with chronic periodontitis and in HEVs of reactive lymph nodes, confirming morphological and functional similarity of HEVs in pathologically altered tissues with those in lymphoid tissues.     

Association Between Periodontal Disease and Overweight and Obesity: A Systematic Review

Background: Periodontitis and obesity are among the most common chronic disorders affecting the world's populations, and recent reviews suggest a potential link between overweight/obesity and periodontitis. However, because of the scarcity of prospective evidence, previous reviews were primarily based on cross‐sectional studies, with only a few longitudinal or intervention studies included. This study's objective is to examine the time‐dependent association between obesity and periodontitis and how weight changes may affect the development of periodontitis in the general population. Therefore, longitudinal and experimental studies that assessed the association among overweight, obesity, weight gain, waist circumference, and periodontitis are reviewed. Methods: Intervention and longitudinal studies with overweight or obesity as exposure and periodontitis as outcome were searched through the platforms PubMed/Medline and Web of Knowledge. Results: Eight longitudinal and five intervention studies were included. Two of the longitudinal studies found a direct association between degree of overweight at baseline and subsequent risk of developing periodontitis, and a further three studies found a direct association between obesity and development of periodontitis among adults. Two intervention studies on the influence of obesity on periodontal treatment effects found that the response to non‐surgical periodontal treatment was better among lean than obese patients; the remaining three studies did not report treatment differences between obese and lean participants. Among the eight longitudinal studies, one study adjusted for C‐reactive protein (CRP) and biologic markers of inflammation such as CRP, interleukin‐6, and tumor necrosis factor‐α, and inflammation markers were analyzed separately in three of the five intervention studies. Conclusion: This systematic review suggests that overweight, obesity, weight gain, and increased waist circumference may be risk factors for development of periodontitis or worsening of periodontal measures.     

The role of inflammatory and immunological mediators in periodontitis and cardiovascular disease

Epidemiological studies have implicated periodontitis (PD) as a risk factor for development of cardiovascular disease (CVD). Persistent infections such as periodontitis induce inflammatory and immune responses which may contribute to coronary atherogenesis, and, in conjunction with other risk factors, may lead to coronary heart disease (CHD). In this review, mechanisms are described that may help explain the association between periodontal infections and CHD. Periodontal diseases are bacterial infections associated with bacteremia, inflammation, and a strong immune response, all of which may represent significant risk factors for the development of atherogenesis, CHD, and myocardial infarction (MI). Several mechanisms may participate in this association, including those induced by oral organisms, and those associated with host response factors. This review will focus on host factors. Oral pathogens and inflammatory mediators (such as interleukin [IL]-1 and tumor necrosis factor [TNF]-alpha) from periodontal lesions intermittently reach the bloodstream inducing systemic inflammatory reactants such as acute-phase proteins, and immune effectors including systemic antibodies to periodontal bacteria. This review will describe the potential role of various inflammatory as well as immunologic factors that may play a role in periodontitis as a possible risk factor for CHD.     

Periodontal disease and the metabolic syndrome

The metabolic syndrome (MetS) is a spectrum of conditions that increase the risk of cardiovascular disease and diabetes mellitus. The components of MetS include dysglycemia, visceral obesity, atherogenic dyslipidemia (elevated triglycerides and low levels of high‐density lipoprotein) and hypertension. An association of periodontal disease and MetS has been suggested. This association is believed to be the result of systemic oxidative stress and an exuberant inflammatory response. When examined individually, the components of the MetS that are most closely related to the risk of periodontitis are dysglycemia and obesity, with lesser contributions by atherogenic dyslipidemia and hypertension. Data suggest that the odds of periodontitis increase with the number of MetS components present in an individual. The direction of the relationship between MetS and periodontal disease cannot currently be determined because the majority of studies are cross‐sectional. The association between MetS and periodontitis, however, suggests that improved understanding of this association could promote interprofessional practice. Evidence suggests that periodontal therapy can reduce the levels of inflammatory mediators in serum. If this finding is confirmed, periodontal treatment could become part of therapy for MetS. Oral health providers who identify patients at risk for MetS could refer them to a medical provider, and physicians could refer patients to dentists to ensure that patients with MetS receive a dental evaluation and any necessary treatment. These clinical activities would improve both oral and general health outcomes.     

Periodontal disease and systemic illness: will the evidence ever be enough?

The concept of focal infection or systemic disease arising from infection of the teeth was generally accepted until the mid‐20th century when it was dismissed because of lack of evidence. Subsequently, a largely silo approach was taken by the dental and medical professions. Over the past 20 years, however, a plethora of epidemiological, mechanistic and treatment studies have highlighted that this silo approach to oral and systemic diseases can no longer be sustained. While a number of systemic diseases have been linked to oral diseases, the weight of evidence from numerous studies conducted over this period, together with several systematic reviews and meta‐analyses, supports an association between periodontitis and cardiovascular disease, and between periodontitis and diabetes. The association has also been supported by a number of biologically plausible mechanisms, including direct infection, systemic inflammation and molecular mimicry. Treatment studies have shown that periodontal treatment may have a small, but significant, systemic effect both on endothelial function and on glycemic control. Despite this, however, there is no direct evidence that periodontal treatment affects either cardiovascular or diabetic events. Nevertheless, over the past 20 years we have learnt that the mouth is an integral part of the body and that the medical and dental professions need to work more closely together in the provision of overall health care for all patients.     

How does the periapical inflammatory process compromise general health?

Several lines of evidence support the causative role of oral inflammatory lesions and certain systemic diseases, such as atherosclerosis and cardiovascular diseases, adverse pregnancy outcome and lung diseases. Properly executed epidemiologic studies identified increased odds ratios. Local or metastatic spread of oral microorganisms, local production of microbial or host‐derived soluble regulatory molecules, that may initiate or sustain inflammatory events in remote tissues and organs and the presence of (a) common – extrinsic‐ or intrinsic‐pathological mechanism(s) may result in or contribute to both local and systemic inflammation. A number of cross‐sectional studies addressing a possible association between oral health and systemic diseases have also investigated the presence or the absence of periapical lesions. However, these studies cannot either confirm or refute a role of the periapical inflammatory lesion in the observed associations, since other variables of oral health might have exerted an inestimable influence on general health of the assessed population. The literature, dealing with patients with root canal infections and apical periodontitis as sole oral inflammatory lesions is extremely sparse. Our group has demonstrated that young adults with apical periodontitis exhibit certain biochemical changes, such as elevated levels of C‐reactive protein and an increased whole blood chemiluminescence, which have been shown to elevate the risk for cardiovascular diseases. Future research will be required to determine whether and to what extent may endodontic diseases affect general health.     

Periodontal diseases and association with atherosclerotic disease

Cardiovascular diseases still account for the majority of deaths worldwide, although significant improvements in survival, after being affected by cardiovascular disease, have been achieved in the last decades. Periodontal diseases are also a common global burden. Several studies have shown a link between cardiovascular disease and periodontitis, although evidence is still lacking regarding the direct cause-effect relation. During the 2012 “Periodontitis and systemic diseases” workshop, the available evidence on the association between cardiovascular and periodontal diseases was discussed, covering biologic plausibility and clinical studies. The objective of the present narrative review was to update the previous reviews presented at the 2012 workshop, following similar methodological approaches, aiming to critically assess the available evidence. With regard to biologic plausibility, two aspects were reviewed: (a) for microbiologic mechanisms, assessing periodontal bacteria as a contributing factor to atherosclerosis based on seven “proofs,” substantial evidence was found for Proofs 1 through 6, but not for Proof 7 (periodontal bacteria obtained from human atheromas can cause atherosclerosis in animal models), concluding that periodontal pathogens can contribute to atherosclerosis; (b) mechanistic studies, addressing five different inflammatory pathways that could explain the links between periodontitis and cardiovascular disease with the addition of some extra pathways , suggest an association between both entities, based on the presence of higher levels of these inflammatory markers in patients with periodontitis and cardiovascular disease, vs healthy controls, as well as on the evidence that periodontal treatment reduces serum levels of these mediators. When evidence from clinical studies was analyzed, two aspects were covered: (a) epidemiologic studies support the estimation that the incidence of atherosclerotic disease is higher in individuals with periodontitis than in individuals with no reported periodontitis, irrespective of many common risk factors, but with a substantial variability in the definitions used in reporting of exposure to periodontal diseases in different studies; (b) intervention trials have shown that periodontal therapy can reduce serum inflammatory mediators, improve the lipids profile, and induce positive changes in other cardiovascular disease surrogate measures, but no evidence is available to support that adequate periodontal therapy is able to reduce the risk for cardiovascular diseases, or the incidence of cardiovascular disease events in periodontitis patients.     

Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers

Severe periodontitis is associated with elevated inflammatory markers in otherwise healthy populations. However, the nature of this association has not been determined. Our aim was to assess whether the degree of response to periodontal therapy was associated with changes in serological markers of systemic inflammation. Ninety-four systemically healthy subjects with severe generalized periodontitis participated in a prospective six-month blind intervention trial. Periodontal parameters and inflammatory markers [C-reactive Protein (CRP) and Interleukin-6 (IL-6)] were evaluated prior to and 2 and 6 mos after delivery of standard non-surgical periodontal therapy. Six months after treatment, significant reductions in serum IL-6 (p < 0.001, median decrease 0.2 ng/L, 95% CI 0.1-0.4 ng/L) and CRP (p < 0.0001, median decrease 0.5 mg/L, 95% CI 0.4-0.7) were observed. Decreases in inflammatory markers were significant in subjects with above average clinical response to periodontal therapy after correction for possible confounders. Periodontitis may add to the systemic inflammatory burden of affected individuals.     

Effects of diabetes mellitus on periodontal and peri-implant conditions: update on associations and risks

Objectives: To review the evidence for the association between diabetes and periodontal and peri-implant conditions and the impact of periodontal therapy in subjects with diabetes.
Material and Methods: A search of MEDLINE-PubMed was performed up to and including December 2007. The search was limited to clinical studies published in English. Publications on animal studies were excluded. The selection criteria included all levels of available evidence.
Results: Evidence on the association between diabetes and periodontitis supports the concept of increased severity but not extent of periodontitis in subjects with poorly controlled diabetes. Subjects with controlled diabetes do not show an increase in extent and severity of periodontitis. Periodontitis is associated with poor glycaemic control and diabetes-related complications. It is inconclusive that periodontal therapy with or without the use of antibiotics results in improvements of glycaemic control and of markers of systemic inflammation. Evidence is lacking to indicate that implant therapy in subjects with diabetes yields long-term outcomes comparable with those of non-diabetic subjects.
Conclusions: Poorly controlled diabetes may be considered a risk factor for increased severity of periodontitis. The effects of periodontal therapy on glycaemic control and systemic inflammation is not proven beyond doubt and need to be confirmed in large-scale randomized-controlled clinical trials.     

Group of serum inflammatory markers and periodontitis-metabolic syndrome coexistence in Koreans

Background: Recent epidemiologic studies have shown that individuals with periodontitis have a significantly increased risk of metabolic syndrome (MetS). Chronic infection and subsequent production of systemic inflammatory markers may be associated with this increased risk. The aim of present study is to determine whether the presence of periodontitis and MetS is associated with a group or an individual of C‐reactive protein (CRP), interleukin (IL)‐1β, IL‐6, IL‐8, tumor necrosis factor‐α (TNF‐α), and homocysteine (HCY) in the serum of a Korean population. Methods: Medical and periodontal parameters, including CRP, IL‐1β, IL‐6, IL‐8, TNF‐α, and HCY, were evaluated in 118 individuals (73 healthy; 20 with periodontitis only; 13 with MetS only; and 12 with both). The community periodontal index was used to assess periodontitis. Age, sex, monthly household income, smoking, and drinking were evaluated as confounders. Analysis of covariance, linear regression analysis, and factor analysis were applied. Results: The group of serologic cytokines was synergistically associated with the periodontitis–MetS coexistence. TNF‐α and IL‐6 were two representing serologic cytokines in the group. Conclusions: Our results suggest that a group of systemic biologic markers represented by TNF‐α and IL‐6 might mediate the association between MetS and periodontitis adjusted for various confounders. Additional evidence is needed to generalize our results more widely.     

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??Alzheimer's disease is the most common form of dementia associated with environmental factors. Periodontitis is a chronic infectious disease that occurs in periodontal supporting tissues. Studies have found a close association between periodontitis and Alzheimer′s disease??but the potential mechanism linking periodontitis with Alzheimer′s disease is not fully clear. It might be that the inflammatory response and vascular changes are the two mediators of the disease??and the common risk factors promote the development of both diseases. The recent findings of the association between periodontitis and Alzheimer′s disease were discussed in this paper.     

牙周炎与阿尔兹海默症相关性研究进展

阿尔兹海默症是一种最常见的老年痴呆症,与环境因素密切相关。牙周炎是发生在牙周支持组织的一种慢性感染性疾病。研究表明,牙周炎与阿尔兹海默症的发生发展密切相关,但作用机制尚未完全明确,炎症反应及血管结构的改变可能是两种疾病的中介,共同的危险因素促进两种疾病的发生发展。文章就近年来牙周炎与阿尔兹海默症相关性的研究进展做一综述。     

The periodontal infection-systemic disease link: a review of the truth or myth

Observational studies indicate periodontal infections as a risk factor for systemic conditions like cardiovascular disease and preterm low birth weight. This paper reviews and argues the biological plausibility for a periodontal infection-systemic disease link and reviews the available experimental data from animal models and human intervention trials. Five principal lines of evidence can be used to explain the biological plausibility of a link. First, infection in general has been implicated in the pathogenesis of both atherosclerosis and preterm delivery. Periodontal infection secondly causes transient and low-grade bacteraemias and endotoxaemias in patients. Thirdly, periodontal infection promotes systemic inflammatory and immune responses that may play roles in disease. Periodontal pathogens express specific virulence factors that can affect atherogenic or parturition events. Lastly, periodontal pathogens have also been isolated from non-oral tissues like atheromatous plaques. Experimental data derived from rodent and pig models indicate that infection or bacteraemias with the periodontal pathogen, Porphyromonas gingivalis, can increase atheroma size or reduce litter weights as compared to controls. While human intervention data are lacking for patients at risk for cardiovascular disease, early data indicate that periodontal therapy administered to pregnant mothers with periodontitis can reduce the incidence of preterm low birth weight deliveries. Nevertheless, more and larger intervention trials are needed before we can fully accept periodontal infection as a true risk factor in the causal pathways of cardiovascular disease and preterm low birth weight.     

Obesity, inflammation, and periodontal disease

The prevalence of obesity has increased substantially over the past decades in most industrialized countries. Obesity is a systemic disease that predisposes to a variety of co-morbidities and complications that affect overall health. Cross-sectional studies suggest that obesity is also associated with oral diseases, particularly periodontal disease, and prospective studies suggest that periodontitis may be related to cardiovascular disease. The possible causal relationship between obesity and periodontitis and potential underlying biological mechanisms remain to be established; however, the adipose tissue actively secretes a variety of cytokines and hormones that are involved in inflammatory processes, pointing toward similar pathways involved in the pathophysiology of obesity, periodontitis, and related inflammatory diseases. We provide an overview of the definition and assessment of obesity and of related chronic diseases and complications that may be important in the periodontist's office. Studies that have examined the association between obesity and periodontitis are reviewed, and adipose-tissue-derived hormones and cytokines that are involved in inflammatory processes and their relationship to periodontitis are discussed. Our aim is to raise the periodontist's awareness when treating obese individuals.     

Association between periodontitis and COVID-19 severity in a tertiary hospital: A retrospective cohort study

IntroductionPeriodontitis is a chronic inflammatory disease caused by biofilm accumulation resulting in loss of periodontal attachment which could be linked to systemic implications. Coronavirus disease of 2019 (COVID-19) is a disease caused by SARS-CoV-2 that triggers damage to the lungs and other organs. COVID-19 and periodontitis share similar risk factors such as smoking, obesity, old age, and diabetes mellitus. Studies noted that periodontitis along with some systemic diseases has increased mortality. Thus, this study aims to examine the association of periodontitis with COVID-19 outcomes.MethodsThis observational study included periodontitis group and non-periodontitis group for COVID-19 outcome assessment. Inclusion criteria were applied to select adults (≥18 years old) who showed at least one dental visit, and were isolated or admitted due to a COVID-19 complication (i.e. in-ward, ICU, or death). Exclusion criteria were patients with no active dental records. The periodontal status was examined from posterior bitewings and panoramic radiographs. The primary outcome assessed was COVID-19 complications versus no admission.Results and discussionThis study was the first of its kind as a retrospective cohort study to assess the association between periodontitis and COVID-19 severity in Riyadh, Saudi Arabia. Our findings revealed that periodontitis is statistically associated with COVID-19 severity. Periodontitis patients were three times more likely to have COVID-19 complications (p = 0.025). Diabetes (p = 0.004) and hypertension (p = 0.016) patients were 3.5 times more likely to have COVID-19 complications.ConclusionUnderstanding the potential association between periodontitis and COVID-19 through systemic inflammation might be a pathway to achieve high quality medical care.