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

心血管疾病(CVD)是女性死亡的主要原因。而绝经前的女性 似乎对心血管疾病具有相对的保护作用，绝经后风险显著增加。性的作用-- 类固醇，特别是雌激素，作为绝经前保护的来源已经被广泛研究； 然而，消息来源仍不得而知。我们建议进行一项流行病学研究，调查抗-HBs 苗勒氏激素(AMH)是一种随绝经而丢失的非雌激素卵巢激素，与 心血管疾病。黄体生成素是一种转化生长因子-β(转化生长因子-β)糖蛋白，在绝经和/或绝经时不存在 双侧卵巢摘除后。我们已经证明AMH蛋白及其受体(AMHR2)存在于 绝经前妇女和灵长类动物的大血管。AMH是一种很好的候选生物标志物 流行病学研究--它在月经周期中的变化是可预测的，并且可以很容易和可靠地在 储存的血清。这项研究的主要目标是确定AMH丢失的早期年龄是否与 随着心血管危险因素的时间变化和冠状动脉钙化(CAC)的发展，发现 这将为阐明作用机制的实验提供有用的流行病学信息(S) 参与女性心血管疾病的发展。我们的主要目标是确定(目标1)是否存在早期损失 AMH的发生与传统CVD危险因素的变化有关，(AIM 2)AMH的早期丢失识别 面临CAC事件风险的女性。为了检验我们的假设，我们将测量AMH和其他生殖 女性在CARDIA第10年或第20年的激素水平。对于这两个目标，我们将使用约532名女性的数据 来自CARDIA，具有重复、广泛和持续的传统心血管疾病风险因素特征 在CARDIA的第16年已经接受了AMH测试。我们的提案包括来自两个种族的女性 集中在一种非雌激素的卵巢激素(即AMH)上，这是第一个有足够力量的研究 前瞻性地确定AMH和CAC之间是否存在关系。我们的方法提供了一个 独特、有效且经济高效的机会来确定临床使用的 绝经前生物标记物(AMH)与心血管疾病危险因素发展过程中的心血管疾病 到亚临床动脉粥样硬化。AMH与传统心脑血管疾病危险因素和/或CAC的关系 可以为一种潜在的新方法提供支持数据，以识别有更高风险的绝经前妇女 后来的心血管疾病。这项拟议的研究可以为改进妇女的心血管疾病预防策略提供见解。 总的来说，拟议的研究可能会增加我们对心血管疾病病因的了解；找到新的途径 用于心血管疾病风险评估、筛查和治疗方法的研究；重要的是，将提供 Wellons博士拥有在卵巢领域建立独立研究生涯所需的初步数据 妇女的老龄化和心血管疾病预防。

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-β) 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.