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 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.     

Circulating Endothelial Progenitor Cells in Periodontitis

Background: Several biologically plausible mechanisms have been proposed to mediate the association between periodontitis and atherosclerotic vascular disease (AVD), including adverse effects on vascular endothelial function. Circulating endothelial progenitor cells (cEPCs) are known to contribute to vascular repair, but limited data are available regarding the relationship between cEPC levels and periodontitis. The aims of this cross‐sectional study are to investigate the levels of hemangioblastic and monocytic cEPCs in patients with periodontitis and periodontally healthy controls and to associate cEPC levels with the extent and severity of periodontitis. Methods: A total of 112 individuals (56 patients with periodontitis and 56 periodontally healthy controls, aged 26 to 65 years; mean age: 43 years) were enrolled. All participants underwent a full‐mouth periodontal examination and provided a blood sample. Hemangioblastic cEPCs were assessed using flow cytometry, and monocytic cEPCs were identified using immunohistochemistry in cultured peripheral blood mononuclear cells. cEPC levels were analyzed in the entire sample, as well as in a subset of 50 pairs of patients with periodontitis/periodontally healthy controls, matched with respect to age, sex, and menstrual cycle. Results: Levels of hemangioblastic cEPCs were approximately 2.3‐fold higher in patients with periodontitis than periodontally healthy controls, after adjustments for age, sex, physical activity, systolic blood pressure, and body mass index (P = 0.001). A non‐significant trend for higher levels of monocytic cEPCs in periodontitis was also observed. The levels of hemangioblastic cEPCs were positively associated with the extent of bleeding on probing, probing depth, and clinical attachment loss. Hemangioblastic and monocytic cEPC levels were not correlated (Spearman correlation coefficient 0.03, P = 0.77), suggesting that they represent independent populations of progenitor cells. Conclusion: These findings further support the notion that oral infections have extraoral effects and document that periodontitis is associated with a mobilization of EPCs from the bone marrow, apparently in response to systemic inflammation and endothelial injury.     

Periodontal Status Affects C‐Reactive Protein and Lipids in Patients With Stable Heart Disease From a Tertiary Care Cardiovascular Clinic

Background: There are scarce data on the impact of the periodontal condition in the control of biomarkers in patients with cardiovascular disease (CVD). The aim of this study is to assess whether periodontal inflammation and tissue breakdown are associated with C‐reactive protein (CRP) and lipids in patients with stable heart disease. Methods: This cross‐sectional study included 93 patients with stable coronary artery disease (57 males; mean age: 63.5 ± 9.8 years) who were in outpatient care for at least 6 months. After applying a structured questionnaire, periodontal examinations were performed by two calibrated periodontists in six sites per tooth at all teeth. Blood samples were collected from patients on the day of periodontal examination to determine levels of CRP, lipids, and glycated hemoglobin. Multiple linear regression models were fitted to evaluate the association among different periodontal and blood parameters controlling for sex, body mass index, glycated hemoglobin, use of oral hypoglycemic drugs, and smoking. Results: Overall, the sample presented high levels of periodontal inflammation and tissue breakdown. Unadjusted mean concentrations of triglycerides (TGs), very‐low‐density lipoprotein cholesterol, and glucose were significantly higher in individuals with severe periodontitis. When multiple linear regression models were applied, number of teeth with clinical attachment loss ≥6 mm and presence of severe periodontitis were significantly associated with higher CRP concentrations. Bleeding on probing was significantly associated with TGs, total cholesterol, and non‐high‐density lipoprotein cholesterol. Conclusion: In this sample of patients with stable CVD, current periodontal inflammation and tissue breakdown are associated with cardiovascular inflammatory markers, such as CRP and lipid profile.     

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.     

New developments in neutrophil biology and periodontitis

Neutrophils have been historically associated with antimicrobial functions in acute infections but are now appreciated as functionally versatile cells with critical roles in chronic inflammation. Recent advances in neutrophil biology have contributed to a better understanding of periodontal disease pathogenesis and, reciprocally, the study of periodontitis has led to important insights into neutrophil regulation and function. Here, the contributions by our group to this field through interdisciplinary collaboration are discussed. The study of leukocyte adhesion deficiency-associated periodontitis has revealed that the connection of neutrophils with destructive inflammation may involve mechanisms beyond the typical bystander injury dogma. In this regard, neutrophils are required for important immunomodulatory functions and their absence from the periodontium leads to dysregulated overproduction of interleukin-17, which drives inflammatory bone loss. We have also discovered that both the production of neutrophils in the bone marrow and their recruitment to peripheral tissues, including the periodontium, are homeostatically regulated by a secreted protein designated developmental endothelial locus-1. However, developmental endothelial locus-1 expression, and hence developmental endothelial locus-1-dependent homeostasis, declines considerably with aging and contributes to an increased susceptibility to periodontitis in old age. Moreover, our work has mechanistically supported the concept that periodontitis is a dysbiotic disease and we have shown that neutrophils become targets of immune subversion by periodontal bacteria in a manner that promotes dysbiosis. The mechanism involves microbial exploitation of key neutrophil receptors (complement C5a receptor-1 and toll-like receptor-2), leading to crosstalk signaling that uncouples neutrophil-mediated killing (which is impaired) from neutrophil-induced inflammation (which is enhanced). These studies have collectively established new mechanisms governing the protective and destructive functions of neutrophils in periodontitis and offered targeted host-modulation approaches for the treatment of periodontal diseases.     

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.     

Two‐dimensional and three‐dimensional models for studying atherosclerosis pathogenesis induced by periodontopathogenic microorganisms

Epidemiological studies have established a clinical association between periodontal disease and atherosclerosis. Bacteremia and endotoxemia episodes in patients with periodontitis appear to link these two diseases by inducing a body‐wide production of cardiovascular markers. The presence of oral bacteria in atherosclerotic lesions in patients with periodontitis suggests that bacteria, or their antigenic components, induce alterations in the endothelium associated with atherosclerosis. Therefore, a causal mechanism explaining the association between both diseases can be constructed using in vitro models. This review presents current experimental approaches based on in vitro cell models used to shed light on the mechanism by which periodontal pathogenic microorganisms, and their antigenic components, induce proatherosclerotic endothelial activity. Monolayer cultures of endothelial vascular or arterial cells have been used to assess periodontal pathogenic bacteria and their antigenic compounds and endothelial activation. However, these models are not capable of reflecting the physiological characteristics of the endothelium inside vascularized tissue. Therefore, the shift from two‐dimensional (2D) cellular models toward three‐dimensional (3D) models of endothelial cells resembling an environment close to the physiological environment of the endothelial cell within the endothelium is useful for evaluating the physiological relevance of results regarding the endothelial dysfunction induced by periodontopathogens that are currently obtained from 2D models. The use of in vitro 3D cellular models can also be relevant to the search for therapeutic agents for chronic inflammatory diseases such as atherosclerosis. Here, we present some strategies for the assembly of 3D cultures with endothelial cells, which is useful for the study of periodontopathogen‐mediated disease.     

Evidence for periodontitis as a tertiary vascular infection

Periodontal infections create an oral wound that serves as a portal for the systemic dissemination of oral pathogens. Clinical assessments of periodontal disease that account for the number and severity of diseased periodontal sites and teeth; including measurements of pocketing, the degree of redness, inflammation and bleeding on probing, can all provide an estimate of the severity of the clinical condition. However, these clinical signs appear inadequate to completely characterize the size, patency and integrity of the periodontal lesion which serves as a portal for systemic exposure. Increasingly, measures of infectious exposure including systemic antibodies, inflammatory mediators and acute phase reactants serve as surrogates or biomarkers for periodontal disease that provide further insight into the linkages between periodontitis and atherogenesis. This review discusses the evidence for systemic inflammatory responses to oral organisms and the potential role of chronic vessel pathology as a manifestation of tertiary periodontal infections.     

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.     

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.     

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.     

Mechanisms involved in the association between periodontal diseases and cardiovascular disease

It is now well accepted that besides the cholesterol associated mechanisms of atherogenesis, inflammation plays a crucial role in all stages of the development of the atherosclerotic lesion. This 'inflammation hypothesis' raises the possibility that through systemic elevations of pro-inflammatory cytokines, periodontal diseases might also contribute to systemic inflammation and, therefore, to atherogenesis. In fact, there is evidence that periodontal diseases are associated with higher systemic levels of high-sensitivity C-reactive protein and a low grade systemic inflammation. This phenomenon has been explained based on mechanisms associated with either the infectious or the inflammatory nature of periodontal diseases. The purposes of this article were to review (1) the evidence suggesting a role for oral bacterial species, particularly periodontal pathogens, in atherogenesis; (2) the potential mechanisms explaining an etiological role for oral bacteria in atherosclerosis; (3) the evidence suggesting that periodontal infections are accompanied by a heightened state of systemic inflammation; (4) the potential sources of systemic inflammatory biomarkers associated with periodontal diseases; and (5) the effects of periodontal therapy on systemic inflammatory biomarkers and cardiovascular risk.     

Periodontal disease and biomarkers related to cardiovascular disease

Periodontal disease is a chronic infection of the gums characterized by a loss of attachment between the tooth and bone, and by bone loss. We evaluated cross-sectionally the association between periodontal disease and C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (t-PA), LDL-C, von Willebrand factor, and soluble tumor necrosis factor receptors 1 and 2. The final sample consisted of 468 men (ages 47-80 yrs), participating in the Health Professional Follow-up Study, who provided blood and were free of CVD, diabetes, and cancer. In multivariate regression models controlling for age, cigarette smoking, alcohol intake, physical activity, and aspirin intake, self-reported periodontal disease was associated with significantly higher levels of CRP (30% higher among periodontal cases compared with non-cases), t-PA (11% higher), and LDL-C (11% higher). Based on our data, periodontal disease showed significant associations with biomarkers of endothelial dysfunction and dyslipidemia, which may potentially mediate the association between periodontal and cardiovascular disease.     

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.     

Severe periodontitis is associated with systemic inflammation and a dysmetabolic status: a case-control study

BACKGROUND AND AIM: A cluster of metabolic factors defines a syndrome that predisposes to diabetes and cardiovascular disease. Chronic infections such as periodontitis might alter these individual metabolic factors and the systemic inflammatory burden. The aim of this study was to investigate the association between severe periodontitis and increase in inflammatory and metabolic risk factors for cardiovascular disease. MATERIALS AND METHODS: We examined 302 patients with severe periodontitis and 183 healthy controls, and we collected a blood sample from each subject in order to investigate differences in inflammatory (leukocyte numbers and differential counts) and metabolic markers (lipids and glucose). RESULTS: After correcting for differences in age, gender, smoking and ethnicity, periodontitis subjects exhibited a low-grade systemic inflammation (increased white cell counts, 1.10+/-1.02 x 10(9)/l, 95%CI 1.05-1.15, p=0.0001), dyslipidemia [lower high-density lipoprotein cholesterol, 1.14+/-1.03 mmol/l, 95%CI 1.08-1.20, p<0.0001 and higher low-density lipoprotein cholesterol, 1.12+/-1.03, 95%CI 1.05-1.19, p<0.0001) and increased non-fasting serum glucose levels (1.04+/-1.01 mmol/l, 95%CI 1.02-1.06, p=0.01) when compared with controls. The associations were confirmed in a subpopulation of Caucasian non-smokers. A trend for a dose dependent effect of the number of periodontal pockets on the tested inflammatory and metabolic markers was observed. Conclusions: These data suggest a possible link between severe generalized periodontitis, systemic inflammation and a dysmetabolic state in otherwise healthy individuals.     

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.     

Periodontal disease and metabolic syndrome: A qualitative critical review of their association

BackgroundMetabolic syndrome (MetS) is a conglomerate of several physical conditions/diseases that, as a group, increases the risk of mortality resulting from development of T2DM and cardiovascular diseases (CVD). These conditions/diseases include glucose intolerance/insulin resistance, hypertension, obesity, and dyslipidemia. The results from epidemiological studies suggest that there is an association between metabolic syndrome (MetS) and periodontitis, it is therefore important to understand the current status of the association and a possible contribution of periodontitis to MetS.ObjectiveThis review will qualitatively analyze published papers on the association of MetS and periodontitis/periodontal disease to clarify the current status of the association and suggest future directions for studies which may unravel the causal relationship between them.ResultsOf 309 papers related to MetS and periodontitis, 26 are original research papers that investigated the relationship/association between periodontal disease and MetS. Criteria used to assess periodontitis and MetS as well as overall study designs and patient recruitment criteria varied greatly among these studies.ConclusionAll these studies demonstrated a positive association between periodontal disease and MetS. However, due to the heterogeneity of criteria to assess periodontitis and MetS and also paucity of longitudinal studies, it is difficult to determine the relative contribution of periodontitis to MetS. Age and the number of positive components of MetS appear to strengthen the relationship, however, incidence of each disease entity increases with ageing. Thus, mechanistic studies are also necessary to unravel the inter-relationship between periodontitis and MetS. In this regard, a use of animal models will be helpful as they are more uniform in regards to genetic background and have minimum confounding factors. Finally, development of accurate, quantitative assessment of gingival inflammation are necessary in order to determine the influence of periodontal disease on the development of MetS and its components.     

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。     

Is There a Causal Link Between Periodontitis and Cardiovascular Disease? A Concise Review of Recent Findings

There is substantial evidence in support of an association between periodontitis and cardiovascular disease. The most important open question related to this association is causality. This article revisits the question of causality by reviewing intervention studies and systematic reviews and meta analyses published in the last 3 years. Where are we now in answering this question? Whilst systematic reviews and epidemiological studies continue to support an association between the diseases, intervention studies fall short in determining causality. There is a dearth of good-quality, blinded randomised control trials with cardiovascular disease outcomes. Most studies use surrogate markers/biomarkers for endpoints, and this is problematic as they may not be reflective of cardiovascular disease status. This review further highlights another issue with surrogate markers/biomarkers: the potential for collider bias. Ethical considerations surrounding nontreatment have led to calls for a well-annotated database containing in-depth dental health data. Finally, a relatively new and important risk factor for cardiovascular disease, clonal haematopoiesis of indeterminate potential, is discussed. Clonal haematopoiesis of indeterminate potential increases cardiovascular risk by more than 40%, and inflammation is a contributing factor. The impact of periodontal disease on this emerging risk factor has yet to be explored. Although the question of causality in the association between periodontal disease and cardiovascular disease remains unanswered, the importance of good oral health in maintaining good heart health is reiterated.