Venous Thromboembolism: Assessing Novel Risk Factors and Treatments

Abstract

Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is the third leading cause of cardiovascular death. This dissertation includes research intended to improve our understanding of two potential risk factors for VTE (body height and endogenous sex hormones) and the comparative safety of novel drugs [direct oral anticoagulants (DOACs)] and warfarin used for treating patients with VTE. Manuscript 1 uses data from two prospective cohorts [the Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS)] and a case-control study (the Mayo Clinic VTE Study) to examine the association between body height and risk of VTE using a Mendelian randomization approach, which may be less influenced by traditional confounding factors. Taller height was associated with an increased risk of VTE. Manuscript 2 uses data from the ARIC study to examine the associations between plasma levels of endogenous testosterone, dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) with incidence of VTE using Cox proportional hazards regression. Plasma hormones were not associated with incidence of VTE among men and postmenopausal women not using exogenous hormones. Lower plasma DHEAS and higher plasma SHBG, when modeled using quartiles, were associated with higher risk of VTE among postmenopausal women using exogenous hormones. Manuscript 3 uses administrative claims data from enrollees in a large, private, nationwide health plan to compare the risk of all-cause mortality during the primary treatment of VTE between groups of enrollees with prescriptions for different oral anticoagulants using marginal structural logistic models. There was no association between having a prescription for warfarin versus any DOAC or between any head-to-head DOAC comparisons with risk of all-cause mortality occurring within 3 or 6 months. This dissertation extends our knowledge on VTE risk factors and the primary treatment of VTE, which could contribute to future preventive efforts and treatment guidelines.