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.     

Cardiovascular disease and periodontitis: an update on the associations and risk

Background: Associations between periodontitis and cardiovascular diseases have been recognized.
Material and Methods: New literature since the last European Workshop on Periodontology has been reviewed.
Results: The lack of reliable epidemiological data on disease prevalence makes an assessment of the associations and risks between periodontitis and cardiovascular diseases difficult. Two recent meta-analysis reports have identified associations between periodontitis and cardiovascular diseases (odds ratios: 1.1–2.2). Different surrogate markers for both disease entities, including serum biomarkers, have been investigated. Brachial artery flow-mediated dilatation, and carotid intima media thickness have in some studies been linked to periodontitis. Studies are needed to confirm early results of improvements of such surrogate markers following periodontal therapy. While intensive periodontal therapy may enhance inflammatory responses and impair vascular functions, studies are needed to assess the outcome of periodontal therapies in subjects with confirmed cardiovascular conditions. Tooth eradication may also reduce the systemic inflammatory burden of individuals with severe periodontitis. The role of confounders remain unclear.
Conclusions: Periodontitis may contribute to cardiovascular disease and stroke in susceptible subjects. Properly powered longitudinal case–control and intervention trials are needed to identify how periodontitis and periodontal interventions may have an impact on cardiovascular diseases.     

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.     

牙周干预措施对动脉粥样硬化影响的实验动物研究

目的模拟牙周炎患者日常生活中的牙周干预措施,研究各种牙周干预措施对SD大鼠动脉粥样硬化(As)发生、发展的影响。方法 SD大鼠随机分为4组:正常对照组(A组)、As组(B组)、As合并牙周炎组(C组)、牙周炎组(D组),将C组根据牙周干预措施不同再分为不治疗组(C1组)、刮治组(C2组)、药物治疗组(C3组)和拔除患牙组(C4组)。对各组进行相应的建模处理,苏木精-伊红染色,光学显微镜下观察牙周组织、颈动脉血管壁组织的病理变化,酶联免疫吸附(ELISA)法检测血清超敏C反应蛋白(hsCRP)的含量。结果病理切片发现B组、C3组和D组颈动脉血管壁均可见大量泡沫细胞形成、聚集;C1组和C4组可见内膜下有钙盐沉积,中膜弹力纤维紊乱、破坏;C2组可见纤维帽的形成及斑块破裂。牙周干预处理后,所有建模组和干预处理组的血清hsCRP含量均较A组明显升高(P<0.05);C1组、C2组、C3组的hsCRP含量较B组明显升高(P<0.05);且C2组hsCRP的含量高于C1组,差异具有统计学意义(P<0.05)。结论对于SD大鼠,无论有无高脂状态,牙周炎均可引起或加重As的发生发展;而在高脂状态下,直接牙周干预都可能加重As病变,其中牙周直接刮治处理的影响在短期内可能会更严重,且hsCRP可能参与了As加重的病变过程。     

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.     

Periodontal diseases and health: Consensus Report of the Sixth European Workshop on Periodontology

Introduction: The remit of this group was to update the knowledge base on periodontal diseases and health.
Material and Methods: The literature was systematically searched and critically reviewed in five specific topics.
Results: Prevalence of periodontitis: The data suggest a trend towards a lower prevalence of periodontitis in recent years.
Adverse pregnancy outcome: The findings indicate a likely association between periodontal disease and an increased risk of adverse pregnancy outcomes. There is no evidence that treating periodontal disease decreases the rate of adverse pregnancy outcomes.
Prevalence and distribution of periodontal pathogens: Genetic analysis of bacteria has demonstrated an unanticipated diversity within species. Carriage rates and particular subsets of these species vary between ethnic groups. Few of these differences can be related to differences in disease prevalence.
Diabetes mellitus: Evidence on the association supports the concept of increased severity but not extent of periodontitis in subjects with poorly controlled diabetes. It is inconclusive that periodontal treatment results in improved metabolic control.
Cardiovascular diseases: Evidence suggests that having periodontitis contributes to the total infectious and inflammation burden and may contribute to cardiovascular events and stroke in susceptible subjects. The impact of periodontal therapy must be further investigated.     

Markers of systemic bacterial exposure in periodontal disease and cardiovascular disease risk: a systematic review and meta-analysis

BACKGROUND: Recent meta-analyses reported a weak association between periodontal disease (PD) on clinical examination and cardiovascular disease (CVD). Systemic bacterial exposure from periodontitis, which correlates poorly with the clinical examination, has been proposed as the more biologically pertinent risk factor. The purpose of this study was to review and analyze the association between PD with elevated systemic bacterial exposure and CVD. METHODS: We searched in the PubMed, Cochrane Controlled Trials Register, EMBASE, and SCOPUS databases for all literature examining PD and CVD. From 10 selected publications, we extracted 12 cohort (N = 5) and cross-sectional (N = 7) studies and included 11 of these in a meta-analysis. With stratified analyses, this resulted in 14 analyses of coronary heart disease (CHD; N = 7), stroke (N = 4), and carotid intima-medial thickening (CIMT; N = 3) as a measure of early atherosclerosis. Systemic bacterial exposure was measured by periodontal bacterial burden (N = 1), periodontitis-specific serology (N = 12), or C-reactive protein (N = 1). RESULTS: Periodontal disease with elevated markers of systemic bacterial exposure was associated strongly with CHD compared to subjects without PD, with a summary odds ratio of 1.75 (95% confidence interval (CI): 1.32 to 2.34; P <0.001). This group was not associated with CVD events or with stroke but was associated with a significant increase in mean CIMT (0.03 mm; 95% CI: 0.02 to 0.04). CONCLUSION: Periodontal disease with elevated bacterial exposure is associated with CHD events and early atherogenesis (CIMT), suggesting that the level of systemic bacterial exposure from periodontitis is the biologically pertinent exposure with regard to atherosclerotic risk.     

Risk factors for atherosclerosis in cases with severe periodontitis

Aim: Studies have reported on an association between cardiovascular disease (CVD) and periodontitis. The purpose of this case–control study was to provide an insight into this association by determining the plasma levels of some risk markers for CVD in cases with periodontitis.
Materials and Methods: Sixty-eight cases with periodontitis, mean age 53.9 (SD 7.9) years, and 48 randomly selected healthy controls, mean age 53.1 (SD 7.9) years, were investigated. Fasting blood plasma was analysed for glucose, lipids, markers systemic inflammation, cytokines and antibodies against heat shock proteins (Hsp). The associations between periodontitis and the various substances analysed in plasma were calculated using a multivariate logistic regression model, which compensated for age, gender, smoking and body mass index.
Results: The regression analyses revealed a significant association between periodontitis and high levels of C-reactive protein (CRP) [odds ratio (OR) 4.0, confidence interval (CI) 1.4–11.4] and fibrinogen (OR 8.7, CI 2.6–28.4), IL-18 (OR 6.5, CI 2.2–19.5), and decreased levels of IL-4 (OR 0.12, CI 0.0–0.5). The study showed increased levels of antibodies against Hsp65 (OR 2.8, CI 1–7.6) and 70 (OR 2.9, CI 1.1–7.8) and decreased levels of antibodies against Hsp60 (OR 0.3, CI 0.1–0.8).
Conclusions: Periodontitis was associated with increased levels of CRP, glucose, fibrinogen and IL-18, and with decreased levels of IL-4.     

Periodontal disease and C-reactive protein-associated cardiovascular risk

BACKGROUND: Periodontitis has been associated with a moderate systemic inflammatory response. Successful periodontal therapy could decrease serum inflammatory parameters. The aim of this report was to explore the outcomes of periodontal therapy in terms of changes in C-reactive protein (CRP)-associated cardiovascular disease (CVD) risk as defined in a recent American Heart Association (AHA) consensus conference. METHODS: Ninety-four systemically healthy subjects suffering from severe generalized periodontitis received standard non-surgical periodontal therapy. Periodontal parameters and serum inflammatory responses [interleukin-6 (IL-6) and CRP] were monitored 2 and 6 months after therapy. RESULTS: At baseline, subjects with more severe and widespread periodontitis had a higher chance of having high CRP-associated CVD risk (OR 5.6, 95% CI 1.2-27.4). Age and body mass index were also significant in the analysis. After therapy, a significant decrease in number of subjects associated with a medium and high CRP-associated risk was observed (p < 0.001 chi(2)), with 40 of 94 subjects displaying a decrease in their class of risk. Patients who had a better oral response to periodontal therapy were also more likely to have decreased their inflammatory risk category (OR 4.8, 95% CI 1.4-15.8) after correcting for age, gender, ethnicity and cigarette smoking. CONCLUSIONS: This study indicated that periodontitis may add to the inflammatory burden of the individual and may result in increased levels of cardiovascular risk based on serum CRP concentrations. These observations will need to be confirmed in a definitive trial. Given the high prevalence of periodontitis in the population, these data would caution physicians to be aware of the possible oral source of an increased inflammatory burden.     

The periodontal-cardiovascular link

Cardiovascular disease (CVD) and periodontitis are common chronic conditions, and the former remains a major contributor to human mortality. Recent attention has focused on a potential link between periodontal disease and CVD. Observational studies consistently indicate that people with destructive periodontitis may be 1.3 to 2 times more likely to have CVD. This association appears to be biologically plausible, and investigations in atherosclerosis animal models demonstrate larger atheroma sizes in animals infected with the periodontal pathogen, Porphyromonas gingivalis, compared with control animals. Although direct intervention data on the effects of periodontal therapy on CVD risk in patients are not currently available, indirect data suggest that mechanical periodontal therapy can decrease surrogate cardiovascular markers such as serum C-reactive protein. After a recent systematic review on the periodontal-cardiovascular link, a consensus panel concluded that patients and clinicians should be informed that periodontal therapy may prevent the onset or progression of CVD.     

A pilot study into measurements of markers of atherosclerosis in periodontitis

BACKGROUND: Periodontitis may be a possible risk factor for atherosclerosis. The current pilot study explored arterial wall thickness and other variables associated with atherosclerosis in healthy subjects with and without periodontitis. METHODS: Patients with moderate (N = 34) and severe periodontitis (N = 15) and controls (N = 14) were recruited. Intima media thickness (IMT) of the common carotid arteries (CCA), internal carotid arteries (ICA), and bifurcations of carotid arteries (BCA) was estimated bilaterally using B-mode ultrasound. An overall IMT was calculated as the mean of these six measurements. C reactive protein (CRP), fibrinogen, and von Willebrand factor (vWf) were measured in plasma as indicators of systemic inflammation and atherosclerotic disease. Microalbuminuria was determined as a marker of endothelial cell dysfunction. RESULTS: IMT for CCA were 0.64, 0.68, and 0.69 mm for control, moderate, and severe periodontitis, respectively (not significant). IMT for BCA did not vary among groups. IMT of ICA was largest for severe periodontitis (0.81 mm); corresponding values for controls and moderate periodontitis were 0.58 and 0.55 mm, respectively (P= 0.023). Severe periodontitis patients had an overall IMT of 0.76 mm, while moderate periodontitis patients and controls had lower values (0.64 and 0.65 mm, respectively; P= 0.153). After adjusting for potential confounding factors, the increased IMT for ICA in severe periodontitis was also significant (Padj = 0.040). CRP (P= 0.020, Padj = 0.050) and vWf (P= 0.019, Padj = 0.013) were higher in periodontitis than controls; microalbuminuria was not different between groups. Power calculations suggest that a 4-fold expansion of the severe patient and control groups will result in a high chance (power level 80%) that a clinically significant association between the overall IMT and periodontitis will be observed. CONCLUSION: The present pilot study indicates that a full study investigating the relationship between periodontitis and atherosclerosis is warranted.     

Systemic effects of periodontitis: lessons learned from research on atherosclerotic vascular disease and adverse pregnancy outcomes

Studies conducted over the past 25 years have focussed on the role of periodontitis, an inflammatory condition of microbial aetiology that destroys the tooth‐supporting tissues, as a systemic inflammatory stressor that can act as an independent risk factor of atherosclerotic vascular disease (AVSD) and adverse pregnancy outcomes (APOs). It has been suggested that periodontitis‐associated bacteraemias and systemic dissemination of inflammatory mediators produced in the periodontal tissues may result in systemic inflammation and endothelial dysfunction, and that bacteria of oral origin may translocate into the feto‐placental unit. Epidemiological studies largely support an association between periodontitis and ASVD/APOs, independently of known confounders; indeed, periodontitis has been shown to confer statistically significantly elevated risk for clinical events associated with ASVD and APOs in multivariable adjustments. On the other hand, intervention studies demonstrate that although periodontal therapy reduces systemic inflammation and improves endothelial function, it has no positive effect on the incidence of APOs. Studies of the effects of periodontal interventions on ASVD‐related clinical events are lacking. This review summarises key findings from mechanistic, association and intervention studies and attempts to reconcile the seemingly contradictory evidence that originates from different lines of investigation.     

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.     

Comparison of toluidine blue-mediated photodynamic therapy and conventional scaling treatment for periodontitis in rats

Background and Objective:  Periodontitis is a disease caused by bacterial infection accompanied with the inflammation of connected tissues and resorption of alveolar bone. The aim of this study was to investigate the in vivo photosensitization of periodontal bacteria in rats and to compare its efficacy with that of routine scaling and root planing.
Material and Methods:  Periodontitis was developed by submerging ligatures at the subgingival region of maxillary molars in 16 rats. Six weeks later, the infection sites were treated either with 1 mg/mL of toluidine blue plus 12 J/cm² red laser irradiation, or by routine scaling and root planing. The therapeutic efficacy was assessed by evaluating the reduction of total bacterial flora and histological changes of periodontal tissues.
Results:  Significant reduction of total bacterial flora was achieved by both photodynamic therapy and conventional therapy. The signs of inflammation that accompanied periodontitis, such as redness, increased plaque index and gingival index values, bleeding on probing and inflammatory cell infiltration, were greatly reduced without any obvious detectable injury to host tissues. Both photodynamic therapy and conventional therapy showed similar therapeutic results.
Conclusion:  Toluidine blue-mediated photodynamic therapy could effectively treat periodontitis in vivo and has high potential in clinical application.     

Periodontal manifestations of systemic disease

Periodontitis is a chronic bacterial infection of the supporting structures of the teeth. The host response to infection is an important factor in determining the extent and severity of periodontal disease. Systemic factors modify periodontitis principally through their effects on the normal immune and inflammatory mechanisms. Several conditions may give rise to an increased prevalence, incidence or severity of gingivitis and periodontitis. The effects of a significant number of systemic diseases upon periodontitis are unclear and often it is difficult to causally link such diseases to periodontitis. In many cases the literature is insufficient to make definite statements on links between certain systemic factors and periodontitis and for several conditions only case reports exist whereas in other areas an extensive literature is present. A reduction in number or function of polymorphonuclear leukocytes (PMNs) can result in an increased rate and severity of periodontal destruction. Medications such as phenytoin, nifedipine, and cyclosporin predispose to gingival overgrowth in response to plaque and changes in hormone levels may increase severity of plaque-induced gingival inflammation. Immuno-suppressive drug therapy and any disease resulting in suppression of the normal inflammatory and immune mechanisms (such as HIV infection) may predispose the individual to periodontal destruction. There is convincing evidence that smoking has a detrimental effect on periodontal health. The histiocytoses diseases may present as necrotizing ulcerative periodontitis and numerous genetic polymorphisms relevant to inflammatory and immune processes are being evaluated as modifying factors in periodontal disease. Periodontitis severity and prevalence are increased in diabetics and worse in poorly controlled diabetics. Periodontitis may exacerbate diabetes by decreasing glycaemic control. This indicates a degree of synergism between the two diseases. The relative risk of cardiovascular disease is doubled in subjects with periodontal disease. Periodontal and cardiovascular disease share many common risk and socio-economic factors, particularly smoking, which is a powerful risk factor for both diseases. The actual underlying aetiology of both diseases is complex as are the potential mechanisms whereby the diseases may be causally linked. It is thought that the chronic inflammatory and microbial burden in periodontal disease may predispose to cardiovascular disease in ways proposed for other infections such as with Chlamydia pneumoniae. To move from the current association status of both diseases to causality requires much additional evidence. Determining the role a systemic disease plays in the pathogenesis of periodontal disease is very difficult as several obstacles affect the design of the necessary studies. Control groups need to be carefully matched in respect of age, gender, oral hygiene and socio-economic status. Many studies, particularly before the aetiological importance of dental plaque was recognised, failed to include such controls. Longitudinal studies spanning several years are preferable in individuals both with and without systemic disease, due to the time period in which periodontitis will develop.     

The association between periodontal diseases and cardiovascular diseases: a state-of-the-science review

Early case-control and cross-sectional studies demonstrating associations between chronic periodontitis and cardiovascular disease (CVD) were quickly followed by secondary analyses of data available from existing longitudinal studies, which indicated that individuals with periodontitis, as determined by clinical measures, were at greater risk for CVD events. Many of these studies contained large numbers of subjects and were adjusted for traditional risk factors. Within the last 18 months, one case-control study and one longitudinal study have reported finding positive associations that were not statistically significant. The earlier studies stimulated a number of studies focused on identifying potential biological mechanisms that might underlie this association. While still early in that process, such studies have implicated a systemic role for oral microorganisms and for the quality and quantity of the host inflammatory response as key biologic processes that may underlie the association of CVD with the clinical manifestation of periodontitis. It is a positive development when changes in our knowledge regarding biologic mechanisms result in reevaluation of past studies, and this reevaluation leads to new studies that incorporate the design elements demanded by this new knowledge. In that spirit, we conclude that all longitudinal studies reported to date can be characterized as follows: none were initially designed to actually test the association of interest; almost all were restricted to clinical measures of periodontitis to index the exposure and lacked measures of infectious burden and host response; and they used a variety of cardiovascular clinical events to index the outcome and did not include subclinical measures of atherosclerosis. In addition, the longitudinal studies that failed to show a significant association between periodontitis and CVD used the least sensitive and crudest clinical measures of periodontal disease. Based upon the current state-of-the-science, all previous studies should be viewed as lacking sufficiently sensitive and comprehensive measures of periodontal disease as a systemic exposure. Since the potential health care impact of this relationship might be extensive, it is time to enter the next phase of research by conducting molecular epidemiology studies that are appropriately designed to test our current understanding of the molecular and cellular mechanisms involved.     

微小RNA介导的牙周炎与动脉粥样硬化相关机制的研究进展

牙周炎是一种主要由菌斑生物膜所引起的牙周支持组织慢性炎症破坏性疾病,与宿主的免疫反应相关。牙周致病菌可通过一过性菌血症进入血液循环系统,引发血管炎症反应,增加心血管疾病患病风险。微小RNA(microRNA)作为近年来小分子RNA的研究热点,可在表观遗传学水平调控基因表达,参与炎症调节。本文综述了牙周致病菌通过microRNA调控免疫炎症反应的机制,从而介导动脉粥样硬化的发生、发展,为牙周炎与动脉粥样硬化疾病关联的分子机制研究提供新的思路。此外,通过探索动脉粥样硬化与牙周炎相关特异性microRNA的表达模式,可为未来诊断或治疗心血管疾病提供新的参考。     

Effects of periodontal therapy on systemic markers of inflammation in patients with metabolic syndrome: a controlled clinical trial

Background: The systemic inflammation in both metabolic syndrome (MetS) and periodontitis is a common denominator of the association of these conditions with higher risk of atherosclerosis. The current study investigates whether periodontal therapy may reduce systemic inflammation in patients with MetS and reduce cardiovascular risk. Methods: A parallel‐arm, double‐blind, randomized clinical trial of 1‐year duration in patients with MetS and periodontitis was conducted. Participants were randomized to an experimental treatment group (ETG) (n = 82) that received plaque control and root planing plus amoxicillin and metronidazole or to a control treatment group (CTG) (n = 83) that received plaque control instructions, supragingival scaling, and two placebos. Risk factors for cardiovascular disease were recorded; serum lipoprotein cholesterol, glucose, body mass index (BMI), C‐reactive protein (CRP) and fibrinogen concentrations, and clinical periodontal parameters were assessed at baseline and every 3 months until 12 months after therapy. The primary and secondary outcomes were changes in CRP and fibrinogen levels, respectively. Results: The baseline patients’ characteristics of both groups were similar. No significant changes in lifestyle factors, frequency of hypertension, BMI, serum lipoprotein cholesterol, and glucose levels were observed during the study period. The periodontal parameters significantly improved in both groups 3 months after therapy (P = 0.0001) and remained lower than baseline up to 12 months. The improvement of periodontal status was significantly greater in the ETG (P = 0.0001). A multiple linear regression analysis, controlled for sex, smoking, hypertension, and extent of periodontitis, demonstrated that CRP levels decreased with time and that this reduction was significant at 9 (P = 0.024) and 12 (P = 0.001) months in both groups, without difference between the groups. Fibrinogen levels significantly decreased in the ETG at 6 and 12 months but not in the CTG. Conclusion: Reduction of periodontal inflammation either with root planing and systemic antibiotics or with plaque control and subgingival scaling significantly reduces CRP levels after 9 months in patients with MetS.     

Periodontitis and atherogenesis: causal association or simple coincidence?

OBJECTIVES: The aim of this study was to assess the systemic effects of treating severe widespread periodontitis in a population of otherwise healthy individuals by examining treatment associated changes in markers of inflammation that are also implicated in cardiovascular atherosclerotic diseases. The potential impact of specific polymorphisms in cytokine genes known to influence both periodontitis and cardiovascular diseases was also examined. MATERIALS AND METHODS: A convenience sample of patients affected with severe generalised periodontitis was enrolled into a prospective single blind longitudinal intervention trial with a 6 months follow-up. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) levels were assessed by high-sensitivity assays. Serological and clinical periodontal parameters were evaluated at baseline, 2 and 6 months after completion of non-surgical periodontal therapy. Results: In the 94 subjects that completed this pilot trial improvements in all clinical periodontal parameters were achieved. These were accompanied with significant reductions in serum IL-6 and CRP concentrations. In a multivariate model, serum CRP levels were significantly associated with the outcome of periodontal treatment after correcting for potential covariates (age, body mass index, gender, smoking) and polymorphisms in the IL-6 (-174 C/G) and IL-1A (-889) genes. A median decrease in serum CRP of 0.5 mg/l (95% CI 0.4-0.7 mg/l) was observed 6 months after completion of periodontal therapy in this population. Subjects with above average response to periodontal therapy (<30 residual pockets and <30% of sites bleeding on probing) accounted for the observed improvement in serum CRP. CONCLUSIONS: Control of periodontitis, achieved with non-surgical periodontal therapy, significantly decreased serum mediators and markers of acute phase response. The significance of the serum response was associated with the half of the population that responded better to non-surgical periodontal therapy. The results of this pilot study indicate that severe generalised periodontitis causes systemic inflammation. This is consistent with a causative role of periodontitis in atherogenesis.     

Periodontitis-induced lipid peroxidation in rat descending aorta is involved in the initiation of atherosclerosis

Background and Objective:  Periodontitis is a risk factor for the development of atherosclerosis. Recent studies indicate that oxidative mechanisms, including lipid peroxidation, are involved not only in periodontitis but also in atherosclerosis. Lipid peroxidation may play an important role in the pathogenesis of atherosclerosis, particularly during its earliest stages. The purpose of this study was to investigate the relationship between lipid peroxidation induced by periodontitis and the initiation of atherosclerosis.
Material and Methods:  Sixteen rats were randomly divided into two groups of eight rats each. Periodontitis was ligature-induced for 4 wk in the experimental group, whereas the control group was left untreated. After the experimental period, the mandibular first molar regions were resected and then subjected to histological analysis and measurement of hexanoyl-lysine expression as an indicator of lipid peroxidation. Descending aorta was used for measuring the levels of hexanoyl-lysine, reactive oxygen species and lipid deposits, and for real-time polymerase chain reaction microarray analysis. The level of hexanoyl-lysine was also measured in serum.
Results:  In the experimental group, the levels of hexanoyl-lysine in periodontal tissue and serum increased. Only aorta samples in the experimental group showed lipid accumulation, with increased expression of hexanoyl-lysine, reactive oxygen species and oxidative stress-related genes (including nitric oxide synthases 2 and 3), whereas the superoxide dismutase 1 gene level was down-regulated.
Conclusion:  In a ligature-induced periodontitis rat model, increased lipid peroxidation was found in serum and aorta as well as in periodontal tissue. Atherosclerosis-related gene expression and histological changes were also stimulated. Periodontitis-induced lipid peroxidation in the aorta may be involved in the early stage of atherosclerosis.