Unique cardiovascular Risk Factors in Women Research and Mentoring Progam

描述(由申请者提供)：这个项目的目标是通过我在女性独特的心血管危险因素方面的研究计划，在以患者为导向的研究中指导初级调查人员。指导目标：在以患者为导向的研究中保持我的指导计划，继续增加进入该领域的女性和少数族裔的数量，并允许我的计划在哈佛CTSA中进一步发展。K24将使我能够实现这些目标，使我能够保持我与最初的K24奖在临床护理和管理时间上的减少。研究项目：这一应用基于两个翻译研究项目：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引起的心血管并发症。对于许多绝经后妇女来说，血管舒缩症状是导致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，雌激素会增加患心血管疾病(CVD)的风险。因此，需要一种更安全的方式来提供这种治疗。我们已经证明，雌激素增加了肾素-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，这种增加与肾脏血流量的下降有关。我们还表明，雌激素增加了血管损伤和盐皮质激素受体的mRNA。我们推测，屈螺酮，一种孕激素，具有类似于孕酮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)的不良血管效应。2)确定是否可以将糖尿病预防计划(DPP)转化为有妊娠期糖尿病(GDM)病史的妇女的社区环境，以降低进展为2型糖尿病(T2 DM)的风险。T2 DM是心血管疾病的主要危险因素，尤其是在女性中。既往有妊娠期糖尿病的妇女进展为T2 DM的风险很高。DPP显示，改变生活方式可以降低患T2 DM的风险。我们推测，在社区环境中提供改良的DPP将有效地减少新近GDM妇女的产后体重滞留。

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.