Cardiovascular disease (CVD) is the leading cause of death among women. While premenopausal women appear relatively protected against CVD, risk increases significantly after menopause. The role of sex- steroids, especially estrogen, as the source of this premenopausal protection has been studied extensively; however, the source remains unknown. We propose an epidemiologic study investigating whether Anti- Mllerian Hormone (AMH), a non-estrogenic ovarian hormone lost with menopause, is associated with CVD. AMH is a transforming growth factor-beta (TGF-?) glycoprotein that is absent at menopause and/or after bilateral ovarian removal. We have shown that AMH protein and its receptor (AMHR2) are present in the large blood vessels of premenopausal women and primates. AMH is a good candidate biomarker for epidemiologic study ? it varies predictably over the menstrual cycle and is easily and reliably measured in stored serum. The primary goal of this study is to establish whether an early age at AMH loss is associated with the timing of CVD risk factor changes and the development of coronary artery calcium (CAC), findings that would provide epidemiologic information useful in experiments to elucidate the mechanism(s) of action involved in CVD development in women. Our primary aims are to determine whether (AIM 1) an early loss of AMH is associated with changes in traditional CVD risk factors, and (AIM 2) early loss of AMH identifies women at risk of incident CAC. To test our hypotheses, we will measure AMH and other reproductive hormones in women at Year 10 or Year 20 of CARDIA. For both aims, we will use data from ~532 women from CARDIA with repeated, extensive, and ongoing traditional CVD risk factor characterization who already underwent AMH testing at Year 16 of CARDIA. Our proposal includes women from two racial groups, focuses on a non-estrogenic ovarian hormone (ie, AMH), and is the first study with sufficient power to prospectively determine the existence of a relationship between AMH and CAC. Our approach offers a unique, effective, and cost-efficient opportunity to determine the link between a clinically-used premenopausal biomarker (AMH) and CVD across the CVD continuum from CVD risk factor development to subclinical atherosclerosis. A relationship between AMH and traditional CVD risk factors and/or CAC could provide supporting data for a potential new way to identify premenopausal women at increased risk of later CVD. The proposed study could provide insights into improving CVD prevention strategies in women. Overall, the proposed study may increase our understanding of the etiologies of CVD; identify new avenues for research on CVD risk assessment, screening, and therapeutic approaches; and importantly, will provide Dr. Wellons with the preliminary data needed to build an independent research career in the field of ovarian aging and cardiovascular disease prevention in women.
More than 35 million women in the United States are between the ages of 30 and 50 and are experiencing ovarian aging that will end in menopause. Our aims are to determine the influence of ovarian aging on the development of cardiovascular disease (CVD) by investigating the relationship between a biomarker of ovarian aging (Anti-Mullerian Hormone) and traditional CVD risk factors and subclinical atherosclerosis in the longitudinal Coronary Artery Risk Development in Young Adults study. Because early menopause is associated with a higher risk of CVD, the number one cause of death in American women, this study will provide important information on whether the pace and severity of ovarian aging before menopause contributes to the development of atherosclerosis, and will inform women and their doctors in their attempts to reduce this potentially deadly process.
| Kim, Catherine; Slaughter, James C; Wang, Erica T et al. (2017) Anti-Müllerian hormone, follicle stimulating hormone, antral follicle count, and risk of menopause within 5 years. Maturitas 102:18-25 |
| Wellons, Melissa F; Matthews, Juliana J; Kim, Catherine (2017) Ovarian aging in women with diabetes: An overview. Maturitas 96:109-113 |
| Jagadeeswaran, Ramasamy; Vazquez, Benjamin A; Thiruppathi, Muthusamy et al. (2017) Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease. Exp Hematol 50:46-52 |
