The purpose of this molecular epidemiological study is to elucidate, with representative populations of US adults, mechanisms of systemic inflammatory response that are associated with elevated risk of cardiovascular disease (CVD) observed among persons with periodontal disease. This nested cross-sectional study will select subjects from the existing Atherosclerosis Risk in Communities (ARIC) study, an ongoing longitudinal cohort study of a random sample of 16,000 people aged 45-64 years in four states. Existing records of clinical periodontal status from the ARIC study will be used to study equal number of subjects across categories of probing pocket depth (PPD) extent scores. Stored serum samples will be analyzed by ELISA for C-reactive protein (CRP- a non-specific acute phase-reactant) and for lipopolysaccharide binding protein (LBP- an endogenous carrier molecule that binds LPS to the CD14 receptor of polymorphonuclear leukocytes, enhancing the release of inflammatory mediators). Those data will be linked to existing ultrasound measurements of intimal wall thickness of the carotid and popliteal arteries, physician diagnoses of acute CVD events, and other risk factors collected in the ARIC study. In addition, data currently are being collected (with no cost to this project) from assays of inflammatory mediators (IL-6, IL-10 and TNFalpha) in gingival crevicular fluid (GCF) and serum in the same subjects. Statistical analyses will evaluate key components of our hypothesized model of periodontal-CVD etiology. Relationships between extent of PPD and GCF inflammatory mediators will be evaluated using least squares regression models that control for other intra-oral conditions and socio-demographic variables. Severity (mean levels) and prevalence (thresholds of clinically meaningful elevation) of serum inflammatory mediators (CRP, IL-6, IL-10 and TNFalpha) will be compared between PPD groups controlling for other mediators (CRP, IL-6, IL-10 and TNFalpha) will be compared between PPD groups controlling for other systemic diseases. Finally, the multivariate models will assess hypothesized synergistic effects between periodontal disease and serum LBP on systemic inflammatory mediators and prevalent CVD.
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