The central hypothesis of this application is that periodontal diseases, which are chronic gram-negative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary artery disease and stroke. Further, this association may be due to an intrinsic underlying inflammatory response trait that places an individual at high risk for developing both periodontal disease and atherosclerosis. In addition, it is suggested that periodontal diseases, once established, provide a biological burden of endotoxin (LPS, lipopolysaccharide) and inflammatory cytokines (especially thromboxane B2 [TxB2], interleukin-1 beta [Il-1b], prostaglandin E2 [PGE2] and tumor necrosis factor alpha [TNFa]) which serve to initiate and exacerbate atherogenesis and thromboembolic events. These hypotheses will be tested by performing a cross-sectional study on 14,000 participants in a longitudinal study of Atherosclerosis Risk in Communities (ARIC) to determine the contribution of periodontal infection variables to existing multivariate models of atherosclerosis. Using a cross-sectional design, periodontal disease variables will be measured including periodontal probing depths and clinical attachment levels. Plaque samples will be collected for storage and later quantitation of Porphyromonas gingivalis and Streptococcus sanguis. Gingival crevicular fluid will be collected for the quantitation of PGE2, TxB2, IL-1 beta and TNFa. Serum samples will be analyzed for whole cell and LPS-specific antibody titers against selected periodontal pathogens. These measures will be used to test associations with clinical measures of heart disease, heart attack, death from heart disease, and direct ultrasound measures of carotid and popliteal intima- media thickening and lesions as well as atherogenic risk factors that continue to be gathered in the ARIC study. More specifically, it will be determined whether the local gingival crevicular fluid levels of TxB2, IL-1b, TNFa and PGE2 are elevated in cases of severe atherosclerotic stenosis and whether elevated levels of these mediators are associated with other atherosclerosis risk factors including elevated serum lipid variables, serum TxB2 and fibrinogen.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Oral Biology and Medicine Subcommittee 1 (OBM)
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University of North Carolina Chapel Hill
Schools of Dentistry
Chapel Hill
United States
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Sen, Souvik; Giamberardino, Lauren D; Moss, Kevin et al. (2018) Periodontal Disease, Regular Dental Care Use, and Incident Ischemic Stroke. Stroke 49:355-362
Naorungroj, S; Slade, G D; Divaris, K et al. (2017) Racial differences in periodontal disease and 10-year self-reported tooth loss among late middle-aged and older adults: the dental ARIC study. J Public Health Dent 77:372-382
Marchesan, Julie T; Jiao, Yizu; Moss, Kevin et al. (2017) Common Polymorphisms in IFI16 and AIM2 Genes Are Associated With Periodontal Disease. J Periodontol 88:663-672
Sanders, A E; Sofer, T; Wong, Q et al. (2017) Chronic Periodontitis Genome-wide Association Study in the Hispanic Community Health Study / Study of Latinos. J Dent Res 96:64-72
Preisser, John S; Marks, Sarah J; Sanders, Anne E et al. (2017) A new way to estimate disease prevalence from random partial-mouth samples. J Clin Periodontol 44:283-289
Maixner, William; Fillingim, Roger B; Williams, David A et al. (2016) Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification. J Pain 17:T93-T107
Zhang, Shaoping; Divaris, Kimon; Moss, Kevin et al. (2016) The Novel ASIC2 Locus is Associated with Severe Gingival Inflammation. JDR Clin Trans Res 1:163-170
Slade, G D; Ohrbach, R; Greenspan, J D et al. (2016) Painful Temporomandibular Disorder: Decade of Discovery from OPPERA Studies. J Dent Res 95:1084-92
Singer, R E; Moss, K; Kim, S J et al. (2015) Oxidative Stress and IgG Antibody Modify Periodontitis-CRP Association. J Dent Res 94:1698-705
Sanders, Anne E; Divaris, Kimon; Naorungroj, Supawadee et al. (2015) Telomere length attrition and chronic periodontitis: an ARIC Study nested case-control study. J Clin Periodontol 42:12-20

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