Norby, Faye2020-09-222020-09-222020-07https://hdl.handle.net/11299/216355University of Minnesota Ph.D. dissertation. July 2020. Major: Epidemiology. Advisor: Aaron Folsom. 1 computer file (PDF); x, 158 pages + 1 supplementary file.Atrial fibrillation (AF), a cardiac arrhythmia, is a major public health problem. AF is largely a disease of advancing age and contributes to other cardiovascular complications. Identification of novel protein biomarkers could advance understanding of AF mechanisms and may improve the prediction of incident AF. Additionally, it is unknown if disparities exist in AF treatment and outcomes in rural versus urban areas of the US. For manuscripts 1 and 2, we used data from the Atherosclerosis Risk in Communities (ARIC) study, a cohort of older-aged adults in the US. For manuscripts 3 and 4, we used a sample of Medicare beneficiaries enrolled from 2011-2016 with residential zip code categorized into 4 rural/urban areas. In the first manuscript, we examined the association of plasma proteins and identified 40 novel protein biomarkers associated with incident AF. These biomarkers provide insight into mechanistic pathways of AF development. In the second manuscript, we derived and validated a series of 5-year incident AF prediction models that are better targeted and calibrated to older populations. Incorporating biomarkers, including proteomics data, into the models improved AF risk prediction. In the third and fourth manuscripts, we examined the initiation of anticoagulation use and compared the risks of subsequent stroke, heart failure, myocardial infarction, and mortality in newly-diagnosed AF patients in rural versus urban areas. Patients in rural areas were more likely to initiate anticoagulant treatment; however, they were less likely to initiate a newer class of anticoagulants compared to those in urban areas. Those in rural areas had modestly higher risk of cardiovascular outcomes and mortality compared to those in urban areas. Proteomics aids in understanding AF mechanisms and improves risk prediction. Future research should validate our prediction models, develop meaningful ways to incorporate protein biomarkers in clinical practice, and focus on improving AF treatment in rural areas.enaginganticoagulantsatrial fibrillationpredictionproteomicsThesis or Dissertation