Fellowship for Joshua Gordon: Epidemiologic evaluation of risk factors for hypertension in postmenopausal women: Periodontal disease, the oral microbiome and systemic inflammation

? DESCRIPTION (provided by applicant): Hypertension (HTN) is a multifactorial disease associated with high morbidity and mortality. While many risk factors for HTN have been identified, they do not adequately predict whether an individual will develop this disease. The overarching goal of this proposal is to expand understanding on possible modifiable factors and their underlying mechanism for HTN in older women. Investigators propose to examine the association between periodontal disease (PD), edentulism (the complete lack of teeth), the oral microbiome, inflammatory profile, and incident HTN in postmenopausal women. Epidemiologic studies have suggested that edentulism and PD may be associated with HTN; however there are no prospective epidemiologic studies that have evaluated this association in postmenopausal women. It is important to study this association in postmenopausal women be- cause HTN, edentulism, and PD are common in this demographic. Aim 1 will assess the prospective association between PD and incident HTN in 46,400 women enrolled in the Women's Health Initiative Observational Study (WHI-OS). A potential mechanism of the association between PD and HTN is inflammation caused by harmful oral microbes. Inflammation has been shown to play a critical role in HTN in animal models. Also, certain cytokines have been independently associated with HTN in epidemiologic studies. Better understanding of the influence inflammation has on HTN could be realized through studies of broader cytokine profiles. Thus, Aim 2 will evaluate the association between inflammatory biomarkers and HTN utilizing data from 893 women enrolled in the Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) observational cohort study, an ancillary study of the WHI-OS. Another important factor in PD is imbalances in the oral microbiome, which may contribute to the inflammatory link between PD and HTN. The association between composition of the oral microbiome and HTN has not been investigated. Aim 3 will assess associations between composition of the oral microbiome and hypertension in the OsteoPerio study. All three aims will be achieved utilizing prospective data and biological samples available in the WHI-OS and OsteoPerio. Aims 2 and 3 will additionally utilize data currently being collected at a 15 year follow-up visit. Overall this grant application proposes to determine whether (1) edentulism and PD, (2) inflammatory biomarkers, and (3) composition of the subgingival microbiome at baseline are associated with increased risk of HTN during follow-up. Achieving these aims will deepen our understanding of the pathogenesis of HTN in older adults in whom HTN exacts enormous health and economic burden. Results could also inform future mechanistic evaluations of HTN, as well as identification of novel intervention targets to enhance population control of HTN and its complications.