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Reproductive history as a surrogate for lifetime exposure to unopposed estrogen and potential mediation of its association with cardiovascular disease by inflammation
Dissertation   Open access

Reproductive history as a surrogate for lifetime exposure to unopposed estrogen and potential mediation of its association with cardiovascular disease by inflammation

Pam Phojanakong
Doctor of Philosophy (Ph.D.), Drexel University
Aug 2019
DOI:
https://doi.org/10.17918/egr3-cy44
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Abstract

Cardiovascular system--Diseases--Risk factors Estrogen Epidemiology Inflammation
Each year, cardiovascular disease (CVD) causes 1 in 3 deaths, killing approximately one woman every 80 seconds. While the burden of CVD can be explained by conventional risk factors (hypertension, smoking, overweight and obesity, diabetes, and elevated cholesterol), between 20 and 50 percent of CVD-related deaths occur among women without conventional risk factors or preexisting disease. Estrogen has been shown to be cardioprotective, however, the exact influence of timing and dosage of exposure over a woman's lifetime remains unclear. Reproductive history has gained prominence as a surrogate measure of estrogen exposure and a "sentinel of chronic disease" -- capturing rapid changes in cardiometabolic profiles. While studies have shown that independent of the natural aging process, reproductive history is associated with CVD risk, the mechanisms that mediate its effect on CVD risk are not fully understood. This dissertation examines how the use of reproductive history as a proxy for lifetime exposure to unopposed estrogen combined with inflammation in impacts the accuracy of CVD risk modelling. The first paper quantifies age at menarche, first pregnancy, and menopause into a measure of duration of unopposed estrogen exposure in women and utilizes this measure of estrogen exposure to assess the association between estrogen exposure and CVD risk. The second paper examines the role of inflammation as a mediator in the relationship between duration of estrogen exposure and CVD risk. The third paper tests the effectiveness of duration of estrogen exposure and inflammation in predicting CVD risk, compared to traditional CVD risk factors.

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