Unique cardiovascular Risk Factors in Women Research and Mentoring Progam

女性研究和指导计划中独特的心血管危险因素

• 批准号: 8610940
• 负责人: Ellen W Seely
• 金额: $ 19.95万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8610940
• 关键词: Address; Adverse effects; Affect; African American; Agreement; Alaska Native; Amputation; Angiotensin II; Animals; Asians; Award; Behavior Therapy; Behavioral; Blindness; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Caring; Cause of Death; Chronic; Clinical; Collaborations; Communities; Community Health Centers; Complications of Diabetes Mellitus; Conjugated Equine Estrogens; Cross-Over Studies; Development; Diabetes Mellitus; Diabetes prevention; End stage renal failure; Estradiol; Estrogen Replacements; Estrogen Therapy; Estrogens; Evaluation; FDA approved; Fall prevention; Forearm; Gestational Diabetes; Goals; Grant; Health; Heart; Heart Diseases; Hispanics; Hormone replacement therapy; Hormones; Hospitals; Hot flushes; Hypertension; Incidence; Individual; Injury; Intervention; Kidney; Limb structure; Massachusetts; Mediating; Mediator of activation protein; Medroxyprogesterone; Menopause; Mentors; Messenger RNA; Mineralocorticoid Receptor; Minority; Morbidity - disease rate; Myocardial Infarction; Native Americans; Neonatal; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Patients; Postmenopause; Postpartum Period; Postpartum Women; Pregnancy; Prevention; Prevention strategy; Progesterone; Progestins; Prospective Studies; Public Health; Quality of life; Randomized; Recommendation; Recording of previous events; Regimen; Renal Blood Flow; Renin-Angiotensin-Aldosterone System; Reporting; Research; Research Personnel; Research Project Grants; Risk; Risk Factors; Risk Reduction; Rodent; Sampling; Stroke; Symptoms; System; Time; Translating; Translational Research; Translations; Vascular Diseases; Vasodilation; Vasomotor; Weight; Woman; Women' s Health; abstracting; base; brachial artery; cardiovascular disorder risk; cardiovascular risk factor; clinical care; community setting; diabetes prevention program; drospirenone; falls; high risk; improved; kidney cortex; lifestyle intervention; patient oriented research; preclinical study; prevent; programs; public health relevance; receptor

DESCRIPTION (provided by applicant): This project has as its goal the mentoring of junior investigators in patient-oriented research through my research program in unique cardiovascular risk factors in women. Mentoring Goal: To maintain my mentoring program in patient-oriented research, continue to increase the number of women and minorities who enter this field and allow my program to further develop within the Harvard CTSA. The K24 will enable me to achieve these goals by allowing me to maintain the decrease in clinical care and administrative time that I achieved with the original K 24 award. Research Projects: This application is based on two translational research projects: 1) The determination of whether a progestin with antimineralocorticoid activity can ameliorate or prevent estrogen-induced cardiovascular complications in postmenopausal women. For many postmenopausal women, vasomotor symptoms are a major cause of decreased quality of life. Estrogen is the only FDA approved treatment for these symptoms. Recent studies have shown that estrogen increases risk for cardiovascular disease (CVD). Therefore, a safer way to provide such therapy is in need. We have shown that estrogen increases renin-angiotensin-aldosterone system activity, a major mediator of vascular dysfunction and that this increase is associated with a fall in renal blood flow. We have also shown that estrogen increases vascular damage and mRNA for the mineralocorticoid receptor. We postulate that drospirenone, a progestin, with antimineralocorticoid activity similar to progesterone, given with estrogen will decrease adverse vascular effects of traditional hormone replacement (estrogen + medroxyprogesterone). 2) The determination of whether the Diabetes Prevention Program (DPP) can be translated into the community setting for women with a history of gestational diabetes (GDM) to reduce the risk of progression to Type 2 diabetes (T2DM). T2DM is a major risk factor for CVD, particularly in women. Women with prior GDM have a high risk of progression to T2DM. The DPP demonstrated that lifestyle modification can decrease the risk for T2DM. We postulate that a modified DPP delivered in a community setting will be effective in decreasing postpartum weight retention in women with recent GDM. PUBLIC HEALTH RELEVANCE: Cardiovascular disease (CVD) is the leading cause of death in US women. Two unique risk factors for CVD are hormone replacement therapy (HRT) and gestational diabetes (GDM). HRT treats menopausal hot flashes but increases CVD risk , and GDM is a major risk factor for Type 2 diabetes which also increases CVD risk in women. This application will determine if there is a safer way to give HRT and an effective way to decrease the number of GDM women who develop Type 2 DM. . (End of Abstract)

描述（由申请人提供）：该项目的目标是通过我的关于女性独特心血管危险因素的研究项目，指导初级研究人员进行以患者为导向的研究。指导目标：维持我在以患者为导向的研究方面的指导计划，继续增加进入该领域的女性和少数族裔的数量，并使我的项目在哈佛 CTSA 内进一步发展。 K24 将使我能够保持通过原始 K 24 奖项实现的临床护理和管理时间的减少，从而使我能够实现这些目标。研究项目：本申请基于两个转化研究项目：1) 确定具有抗盐皮质激素活性的孕激素是否可以改善或预防绝经后妇女雌激素诱发的心血管并发症。对于许多绝经后妇女来说，血管舒缩症状是生活质量下降的主要原因。雌激素是 FDA 批准的唯一治疗这些症状的药物。最近的研究表明雌激素会增加心血管疾病（CVD）的风险。因此，需要一种更安全的方法来提供此类治疗。我们已经证明，雌激素会增加肾素-血管紧张素-醛固酮系统的活性，这是血管功能障碍的主要介质，并且这种增加与肾血流量的下降有关。我们还表明，雌激素会增加血管损伤和盐皮质激素受体的 mRNA。我们假设屈螺酮（一种孕激素）具有与黄体酮相似的抗盐皮质激素活性，与雌激素一起服用将减少传统激素替代（雌激素+甲羟孕酮）对血管的不良影响。 2) 确定糖尿病预防计划 (DPP) 是否可以转化为针对有妊娠糖尿病 (GDM) 病史的女性的社区环境，以降低进展为 2 型糖尿病 (T2DM) 的风险。 T2DM 是 CVD 的主要危险因素，尤其是女性。既往患有 GDM 的女性进展为 T2DM 的风险很高。 DPP 证明，改变生活方式可以降低患 T2DM 的风险。我们假设在社区环境中提供的改良 DPP 将有效减少近期 GDM 女性的产后体重滞留。 公共卫生相关性： 心血管疾病（CVD）是美国女性死亡的主要原因。 CVD 的两个独特危险因素是激素替代疗法 (HRT) 和妊娠期糖尿病 (GDM)。 HRT 可治疗更年期潮热，但会增加 CVD 风险，而 GDM 是 2 型糖尿病的主要危险因素，也会增加女性 CVD 风险。该应用程序将确定是否有更安全的 HRT 方法以及是否有有效的方法来减少 GDM 女性患 2 型 DM 的数量。 。 （摘要完）

项目成果

Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study.

• DOI: 10.1016/j.ajog.2014.09.031
• 发表时间: 2015-03
• 期刊: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
• 影响因子: 9.8
• 作者: Bateman, Brian T.;Huybrechts, Krista F.;Fischer, Michael A.;Seely, Ellen W.;Ecker, Jeffrey L.;Oberg, Anna S.;Franklin, Jessica M.;Mogun, Helen;Hernandez-Diaz, Sonia
• 通讯作者: Hernandez-Diaz, Sonia

Outpatient calcium-channel blockers and the risk of postpartum haemorrhage: a cohort study.

门诊钙通道阻滞剂和产后出血的风险：一项队列研究。

• DOI: 10.1111/1471-0528.12428
• 发表时间: 2013
• 期刊: BJOG : an international journal of obstetrics and gynaecology
• 作者: Bateman,BT;Hernandez-Diaz,S;Huybrechts,KF;Palmsten,K;Mogun,H;Ecker,JL;Seely,EW;Fischer,MA
• 通讯作者: Fischer,MA

Smoking cessation and associated risk of metabolic syndrome in women.

女性戒烟和代谢综合征的相关风险。

• DOI: 10.2217/whe.12.31
• 发表时间: 2012
• 期刊: Women's health (London, England)
• 作者: Saxena,AditiR;Seely,EllenW
• 通讯作者: Seely,EllenW

Editorial overview: the adrenal cortex.

编辑概述：肾上腺皮质。

• DOI: 10.1097/med.0b013e3283537f0b
• 发表时间: 2012
• 期刊: Current opinion in endocrinology, diabetes, and obesity
• 作者: Seely,EllenW

Breathing life into the lifecourse approach: pregnancy history and cardiovascular disease in women.

• DOI: 10.1161/hypertensionaha.110.156810
• 发表时间: 2010-09
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Rich-Edwards JW;McElrath TF;Karumanchi SA;Seely EW
• 通讯作者: Seely EW