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. .

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Special Emphasis Panel (ZHL1-CSR-R (O1))
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Ludlam, Shari
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Brigham and Women's Hospital
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Manosroi, Worapaka; Tan, Jia Wei; Rariy, Chevon M et al. (2017) The Association of Estrogen Receptor-? Gene Variation With Salt-Sensitive Blood Pressure. J Clin Endocrinol Metab 102:4124-4135
Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J et al. (2017) Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations. Obstet Gynecol 129:174-184
Skurnik, Geraldine; Hurwitz, Shelley; McElrath, Thomas F et al. (2017) Labor therapeutics and BMI as risk factors for postpartum preeclampsia: A case-control study. Pregnancy Hypertens 10:177-181
Nicklas, Jacinda M; Zera, Chloe A; Lui, Janet et al. (2017) Patterns of gestational diabetes diagnosis inside and outside of clinical guidelines. BMC Pregnancy Childbirth 17:11
Skurnik, Geraldine; Roche, Andrea Teresa; Stuart, Jennifer J et al. (2016) Improving the postpartum care of women with a recent history of preeclampsia: a focus group study. Hypertens Pregnancy 35:371-81
Nicklas, Jacinda M; Skurnik, Geraldine; Zera, Chloe A et al. (2016) Employing a Multi-level Approach to Recruit a Representative Sample of Women with Recent Gestational Diabetes Mellitus into a Randomized Lifestyle Intervention Trial. Matern Child Health J 20:261-9
Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J et al. (2016) Late Pregnancy ? Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia. Pediatrics 138:
Zera, Chloe A; Bates, David W; Stuebe, Alison M et al. (2015) Diabetes Screening Reminder for Women With Prior Gestational Diabetes: A Randomized Controlled Trial. Obstet Gynecol 126:109-14
Bateman, Brian T; Hernandez-Diaz, Sonia; Fischer, Michael A et al. (2015) Statins and congenital malformations: cohort study. BMJ 350:h1035
McGinn, Aileen P; Lee, Linda S; Baez, Adriana et al. (2015) Mentoring in Clinical-Translational Research: A Study of Participants in Master's Degree Programs. Clin Transl Sci 8:746-53

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