Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Traditions of Excellence: Horizons of Change University of Manitoba Faculty of Dentistry Anthony M. Iacopino Dean Professor, Restorative Dentistry Periodontitis and Systemic Disease “The Perio-Systemic Connection” Basic Overview Alzheimer Society of Manitoba Winnipeg – March 10, 2008 Relationship Between Periodontitis and Systemic Diseases/Conditions • respiratory disease • arthritis • Alzheimer’s disease • stroke • adverse pregnancy outcome • heart disease • diabetes • osteoporosis Grand Rounds in Oral Systemic Medicine Gapski and Cobb 1(1):14-23, 2006; Moritz and Mealy 1(2):13-21, 2006; Iacopino 1(3):25-37, 2006; Paquette 1(4):14-25, 2006; Tae-Ju Oh et al., 2(1):10-21, 2007 Periodontal Disease: Periodontitis (Socransky et al., J Periodontol 63:322-331, 1992; Liljenberg et al., J Clin Periodontol 21:720-727, 1994) Chronic inflammatory disease • • • • • primarily gram negative anaerobic oral infection gingival inflammation destruction of periodontal supporting tissues exfoliation of teeth in severe cases organisms within microbial flora of dental plaque are the major etiologic agents (Porphyromonas gingivalis, Bacteriodes forsythus, and Treponema denticola) • microorganisms and endotoxins generate localized host-mediated tissue destructive immune response (cellular, inflammatory cytokines) Periodontitis: Systemic Effects Transient bacteremia/endotoxemia • demonstrations of periodontitis-induced bacteremia/endotoxemia linked to periodontitis severity and periods of progression/exacerbation • organisms invade deep connective tissues/endothelium and coronary vasculature • tissue destructive responses not limited to oral cavity Periodontitis: Systemic Effects Transient bacteremia/endotoxemia • creates systemic “exposure” • elevation of serum pro-inflammatory cytokines and acute phase reactants have many biologic effects – leads to elevations of serum lipid levels (FFA, LDL/TRG) – “systemic inflammatory state” may adversely effect many organ systems leading to systemic diseases/conditions associated with chronic inflammation Periodontitis: Systemic Effects (Al-Emadi et al., Quintessence Int 37: 761-765, 2006) Link to systemic health • determined prevalence of systemic diseases/conditions in patients with periodontitis • 420 random patients over a two-year period with periodontal disease) • hypertension, respiratory disease, diabetes, and arthritis significantly more prevalent in subjects with periodontitis (p < 0.05) • subjects with more severe periodontitis were four times more likely to have three or more systemic conditions Periodontitis: Systemic Effects (Albert et al., BMC Health Services Res 6: 103-109, 2006) Link to medical costs • investigated effect of periodontal treatment on medical expenditures for diabetes, cardiovascular disease, and cerebrovascular disease • measured per member per month costs for 144,225 enrollees of a PPO by aggregating ICD-9 expenditures over a two-year period • controlled for differences in disease burden between groups with and without history of periodontal care • periodontal treatment significantly decreases medical costs (p < 0.05) with greater reductions when care is provided earlier in life Periodontitis Causes Systemic Inflammation (D’Aiuto et al., J Clin Perio 34:124-129, 2007) Treatment of periodontitis reverses systemic inflammation • 65 healthy subjects with severe generalized PD • blinded randomized control clinical trial • measured CRP, IL-6, LDL cholesterol at baseline and two months after treatment (standard therapy) – at baseline, markers were significantly elevated – after treatment, significant reductions in CRP (p=0.03), IL-6 (p=0.006), and LDL (p=0.002) – reductions were independent of age, gender, BMI, ethnicity Respiratory Disease Direct linkages through aspiration • aspiration pneumonia – major cause of morbidity, hospitalization, and mortality in institutional settings (~50% of all infections) – tremendous health care costs and decreased quality of life – frequently caused by gram negative organisms in dental plaque around diseased teeth/poorly maintained dentures – indisputable evidence and acceptance by medical community – requires changes in interprofessional patient management Rheumatoid Arthritis Some preliminary studies indicate: • patients with PD and RA exhibit similar proinflammatory cytokine profiles • periodontal pathogens may initiate formation of rheumatoid factor immune complexes • patients with moderate to severe periodontitis are at higher risk for rheumatoid arthritis • dose-response relationship between PD and RA • periodontal treatment reduces the severity of rheumatoid arthritis • requires further investigation, may warrant closer monitoring of periodontal status of RA patients Stroke/CVA/TIA Several credible studies indicate PD is a significant risk factor for CVAs, especially stroke • dose-response relationship (gingivitis, PD severity) • closely tied to mechanisms underlying initiation and progression of atherosclerosis – – – – – dysregulation of lipid metabolism interaction of periodontal pathogens with vascular walls endothelial cell dysfunction and damage initiation and/or exacerbation of atheroma formation thickening of intimal-medial vessel walls Stroke/CVA/TIA (Lee et al., J Periodontol 77:1744-1754, 2006) Periodontitis associated with stroke in the elderly, even partially edentulous patients • NHANES III database for patients aged ≥ 60 years • used “new” index to account for number of teeth – weighs “exposure burden” based on past periodontitis • periodontitis significantly associated with stroke – relationship just as strong for subjects with few teeth – “cumulative effects” of periodontitis are important Cardiovascular Disease 8 separate longitudinal studies from 2000-2004 indicated that PD is associated with the onset of coronary heart disease • controlled for other established risk factors • periodontitis associated with intimal-medial wall thickness (a measure of sub-clinical atherosclerosis) • links between systemic inflammation, PD, and atherosclerosis/CHD as gingival index and dental infections (microbial burden) were positively correlated to onset of new CHD events Cardiovascular Disease Since 2000: • 16 associative studies linking PD to presence of vascular plaques • 9 studies demonstrating presence of periodontal pathogens in atheromas • 16 associative studies concerning inflammatory PDcardiovascular mechanistic link – significant association between PD-induced elevations in serum inflammatory biomarkers (pro-inflammatory cytokines, CRP, fibrinogen) and CHD – levels of inflammatory biomarkers and extent of CHD directly proportional to PD severity – treatment of PD reduces levels of serum inflammatory biomarkers Diabetes The most well defined perio-systemic connection • The “sixth major complication” of diabetes • similar changes in systemic physiology and blood biochemistry (a bi-directional relationship between pro-inflammatory cytokines and serum lipids) • definitive evidence that uncontrolled diabetes exacerbates PD and that PD exacerbates some diabetic complications (reversible with treatment of PD) • preliminary evidence that untreated PD may actually cause diabetes in otherwise healthy patients Periodontitis and Insulin Resistance Recent studies demonstrate links between PD and insulin resistance (case control and randomized trials) • PD causes insulin resistance and significant elevations in serum glucose/HbA1c levels (degree of insulin resistance directly related to severity of PD) • treatment of PD improves glycemic status in diabetic patients (significant decreases in serum glucose/HbA1c levels, reduced insulin requirements, effects more pronounced for severe PD) • significantly more PD in non-diabetic patients with documented insulin resistance • documented relationship between PD and pre-diabetes (impaired fasting glucose and impaired glucose tolerance) Osteoporosis Conflicting results from initial studies for: • periodontal status and systemic bone mineral density • BMD and number of remaining teeth • systemic bone loss as a predictor of risk for alveolar bone loss (vice-versa) Positive studies outnumber negative studies for associations/relationships Both conditions involve physiologic mechanisms mediated through pro-inflammatory cytokines Current thought is that patients would benefit from “bi-directional” screening Alzheimer’s Disease Inflammatory hypothesis (no biologic evidence) • systemic inflammation associated with signals that cross blood-brain barrier via perivascular macrophages/microglia • activated macrophages/microglia initiate a neuroinflammatory process • resultant neuro-inflammatory responses and secretion of neurotoxic factors cause cell injury/death • chronic inflammation in the brain destroys sufficient neurons to cause the clinical signs of dementia • several recent population-based, prospective cohort studies have demonstrated that serum CRP and proinflammatory cytokine levels are increased prior to the clinical onset of dementia Linkage Between PD and Systemic Diseases/Conditions in the Elderly Respiratory Infection Aspiration Periodontitis Dementia Microglia Activation Atherosclerosis Bacteremia Elevated Serum Hyperlipidemia Endotoxemia Pro-Inflammatory Altered Lipid Cytokines Metabolism Rheumatoid Factor Synovial Inflammation Atherosclerosis β-Cell Destruction Insulin Resistance Arthritis Diabetes Vascular Endothelium Iacopino, Grand Rounds Oral-Sys Med 1(3):25-37, 2006 Cardiovascular/ Cerebrovascular Disease Traditions of Excellence: Horizons of Change University of Manitoba Faculty of Dentistry Questions, Comments, Concerns?