Several studies suggest that certain infections, including periodontal infections, predispose to atherosclerotic disease. INVEST has contributed significantly to this field. In INVEST period one, we have found that periodontal disease is cross-sectionally associated with carotid artery intima media thickness (IMT). We have further reported that bacteria presumptively causally related to clinical periodontal disease are related positively to IMT, while those associated with periodontal health are not. In INVEST period 2, we demonstrated that progression of atherosclerosis parallels the longitudinal course of the periodontal infections, after adjustment for cardiovascular risk factors, thus establishing a plausible time sequence of periodontal infection and vascular disease, an essential component in attributing causality. Having confirmed our hypothesis that periodontal disease correlates with atherosclerosis both cross-sectionally and prospectively, we now aim to answer the next two critical questions related to causal inference: Does the relationship of periodontal disease with atherosclerosis translate into clinical CVD events? And is periodontal intervention capable of impacting atherosclerotic progression in a subset of our cohort? We propose a novel design within our ongoing cohort to answer both questions. Thus, our first aim is to continue followup of our cohort of 1,014 alive subjects to provide the first evidence of direct association between periodontal microbiology and incident clinical vascular events, beyond subclinical atherosclerosis.
Our second aim i s to concurrently assess among a random sample of cohort participants(<75yrs), whether achieving and maintaining periodontal health modifies the trajectory of IMT, compared to the regularly followed cohort participants of the same age. This proposal represents the logical culmination of 10 years of research, where we are on the threshold of definitive answers in a population where: i) we have preliminary data supporting the notion that periodontal bacterial colonization levels can predict incident CVD events;ii) parallel progression of both periodontal disease and carotid atherosclerosis have been quantified;and iii) our ability to follow and retain participants has been demonstrated. Our collaborative team of investigators in the fields of periodontology, neurology, CVD epidemiology and biostatistics has been maintained. We thus propose to continue to build on the unique opportunity of our joint efforts in an on-going randomly selected cohort in northern Manhattan where Blacks, Whites and Hispanics have already been thoroughly medically examined and evaluated at baseline and followup for known risk factors for atherosclerosis and stroke, clinical and microbiological periodontal status and host immunologic response. Our study represents a cost-effective, methodologically robust approach, systematically laying the missing blocks for causal inference.

Public Health Relevance

The goal of this proposal is to continue followup of a large tri-ethnic (60% Hispanic, 60% females) cohort to see if the relationship between periodontal infections and subclinical atherosclerosis translates into an increased risk of heart attacks, strokes and vascular deaths;and to test whether achieving and maintaining periodontal health modifies the trajectory of atherosclerosis among persons<75 years-old. This information is of critical public health importance as the US population is aging and periodontal disease is so prevalent.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Atkinson, Jane C
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Columbia University (N.Y.)
Public Health & Prev Medicine
Schools of Public Health
New York
United States
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Rundek, Tatjana; Brown, Devin L (2014) Socioeconomic status and subclinical atherosclerosis: are we closing disparity gaps? Stroke 45:948-9
Arora, Nidhi; Papapanou, Panos N; Rosenbaum, Michael et al. (2014) Periodontal infection, impaired fasting glucose and impaired glucose tolerance: results from the Continuous National Health and Nutrition Examination Survey 2009-2010. J Clin Periodontol 41:643-52
Thai, Ashley; Papapanou, Panos N; Jacobs Jr, David R et al. (2014) Periodontal infection and cardiorespiratory fitness in younger adults: results from continuous national health and nutrition examination survey 1999-2004. PLoS One 9:e92441
Demmer, Ryan T; Zuk, Aleksandra M; Rosenbaum, Michael et al. (2013) Prevalence of diagnosed and undiagnosed type 2 diabetes mellitus among US adolescents: results from the continuous NHANES, 1999-2010. Am J Epidemiol 178:1106-13
Demmer, Ryan T; Trinquart, Ludovic; Zuk, Aleksandra et al. (2013) The influence of anti-infective periodontal treatment on C-reactive protein: a systematic review and meta-analysis of randomized controlled trials. PLoS One 8:e77441
Lorenz, Matthias W; Polak, Joseph F; Kavousi, Maryam et al. (2012) Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data. Lancet 379:2053-62
Demmer, Ryan T; Molitor, Jerry A; Jacobs Jr, David R et al. (2011) Periodontal disease, tooth loss and incident rheumatoid arthritis: results from the First National Health and Nutrition Examination Survey and its epidemiological follow-up study. J Clin Periodontol 38:998-1006
Demmer, Ryan T; Pavlidis, Paul; Papapanou, Panos N (2010) Bioinformatics techniques in microarray research: applied microarray data analysis using R and SAS software. Methods Mol Biol 666:395-417
Demmer, Ryan T; Desvarieux, Moise; Holtfreter, Birte et al. (2010) Periodontal status and A1C change: longitudinal results from the study of health in Pomerania (SHIP). Diabetes Care 33:1037-43
Demmer, Ryan T; Papapanou, Panos N; Jacobs Jr, David R et al. (2010) Evaluating clinical periodontal measures as surrogates for bacterial exposure: the Oral Infections and Vascular Disease Epidemiology Study (INVEST). BMC Med Res Methodol 10:2

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