Trajectory of Anti-Mullerian Hormone Decline and CVD Risk in CARDIA Women

Vanderbilt University Medical Center, Nashville TN

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Abstract

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- Müllerian 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.