Unique cardiovascular Risk Factors in Women Research and Mentoring Progam

描述（由申请人提供）：本项目的目标是通过我对女性独特心血管危险因素的研究项目，指导初级研究者进行以患者为导向的研究。指导目标：保持我的指导项目在以患者为导向的研究中，继续增加进入这一领域的女性和少数族裔的人数，并允许我的项目在哈佛CTSA内进一步发展。K24将使我能够实现这些目标，使我能够保持临床护理和管理时间的减少，这是我在最初的K24奖项中实现的。研究项目：本申请基于两个转化研究项目：1)确定具有抗矿化皮质激素活性的黄体酮是否可以改善或预防绝经后妇女雌激素诱导的心血管并发症。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这种治疗。我们已经证明，雌激素增加肾素-血管紧张素-醛固酮系统的活性，这是血管功能障碍的主要媒介，而且这种增加与肾血流量的下降有关。我们还表明，雌激素增加血管损伤和矿皮质激素受体的mRNA。我们假设，屈螺酮是一种黄体酮，具有与黄体酮相似的抗矿化皮质激素活性，与雌激素一起服用可以减少传统激素替代（雌激素+甲羟黄体酮）对血管的不良影响。2)确定糖尿病预防计划（DPP）是否可以转化为有妊娠糖尿病（GDM）病史的妇女的社区环境，以降低进展为2型糖尿病（T2DM）的风险。2型糖尿病是心血管疾病的主要危险因素，尤其是在女性中。既往患有GDM的女性发展为T2DM的风险很高。DPP表明，生活方式的改变可以降低患2型糖尿病的风险。我们假设在社区环境中进行改良的DPP治疗可以有效降低近期GDM妇女的产后体重潴留。

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.