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

CARDIA 女性抗苗勒氏管激素下降和 CVD 风险的轨迹

• 批准号: 9228566
• 负责人: Melissa Fair Wellons
• 金额: $ 8.34万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9228566
• 关键词: AMHR2 gene; Age; Aging; American; Atherosclerosis; Basic Science; Bilateral; Biological Markers; Blood Vessels; Blood specimen; Calcium; Cardiovascular Diseases; Cause of Death; Cohort Studies; Conjugated Equine Estrogens; Coronary Artery Risk Development in Young Adults Study; Coronary artery; Data; Development; Diastolic blood pressure; Epidemiologic Studies; Epidemiology; Estrogen Replacements; Estrogen Therapy; Estrogens; Etiology; Event; Excision; Family; Glucose; Glycoproteins; Goals; Gonadal Steroid Hormones; Growth; Health; High Density Lipoprotein Cholesterol; High Risk Woman; Hormones; Lead; Link; Longitudinal Studies; Low-Density Lipoproteins; Measurement; Measures; Menopause; Menstrual cycle; Myocardial Infarction; Ovarian; Ovarian hormone; Ovary; Pilot Projects; Pituitary Gland; Postmenopause; Premature Menopause; Premenopause; Prevention strategy; Primates; Process; Progesterone; Property; Proteins; Race; Research; Risk; Risk Assessment; Risk Factors; Role; Serum; Severities; Smoking History; Source; Stroke; Testing; Therapeutic; Time; Transforming Growth Factor beta; Triglycerides; United States; United States National Institutes of Health; Woman; Women' s Group; biracial; candidate marker; cardiovascular disorder prevention; cardiovascular disorder risk; career; clinically significant; cohort; cost efficient; design; experience; follow-up; high risk; improved; insight; middle age; mullerian-inhibiting hormone; new therapeutic target; prevent; racial diversity; randomized trial; receptor; reproductive hormone; research study; screening; young adult

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.

心血管疾病是妇女死亡的主要原因。而绝经前妇女 相对而言，对CVD的保护作用相对较小，但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，已被广泛研究; 但来源不明。我们提出了一项流行病学研究，调查是否抗- 苗勒管激素（AMH）是一种非雌激素性卵巢激素，随着绝经而丢失， CVD。AMH是一种转化生长因子-β（TGF-β）糖蛋白，在绝经期和/或绝经后不存在， 双侧卵巢切除后。我们已经证明AMH蛋白及其受体（AMHR 2）存在于 绝经前妇女和灵长类动物的大血管。AMH是一个很好的候选生物标志物， 流行病学研究-它在月经周期中可预测地变化，并且在月经周期中容易且可靠地测量。 储存的血清本研究的主要目的是确定早期AMH丢失是否与 随着CVD危险因素变化的时间和冠状动脉钙（CAC）的发展， 这将提供流行病学信息，有助于实验阐明作用机制 参与女性CVD的发展。我们的主要目标是确定（目标1）早期损失 AMH与传统CVD危险因素的变化相关，（AIM 2）AMH的早期丢失可识别 有CAC风险的女性。为了验证我们的假设，我们将测量AMH和其他生殖系统。 在10年或20年的CARDIA女性激素。对于这两个目标，我们将使用约532名妇女的数据 来自具有重复、广泛和持续的传统CVD风险因素特征的CARDIA， 已经在CARDIA的第16年进行了AMH测试。我们的提案包括来自两个种族的妇女 小组，重点是非雌激素卵巢激素（即AMH），是第一个研究有足够的权力 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、有效和具有成本效益的机会，以确定临床使用的 绝经前生物标志物（AMH）和CVD从CVD风险因素发展到CVD连续体 亚临床动脉粥样硬化AMH与传统CVD危险因素和/或CAC之间的关系 可能为一种潜在的新方法提供支持数据，以确定绝经前妇女的风险增加， 后来的CVD。这项拟议的研究可以为改善女性CVD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CVD病因的理解;确定新的途径 用于CVD风险评估、筛查和治疗方法的研究;重要的是，将提供 博士Wellons提供了在卵巢癌领域建立独立研究事业所需的初步数据。 女性衰老和心血管疾病预防。