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))
Program Officer
Ludlam, Shari
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Brigham and Women's Hospital
United States
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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
Carter, Ebony Boyce; Stuart, Jennifer J; Farland, Leslie V et al. (2015) Pregnancy Complications as Markers for Subsequent Maternal Cardiovascular Disease: Validation of a Maternal Recall Questionnaire. J Womens Health (Larchmt) 24:702-12
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
Jones, Emily J; Peercy, Michael; Woods, J Cedric et al. (2015) Identifying postpartum intervention approaches to reduce cardiometabolic risk among American Indian women with prior gestational diabetes, Oklahoma, 2012-2013. Prev Chronic Dis 12:E45
Bateman, Brian T; Huybrechts, Krista F; Maeda, Ayumi et al. (2015) Calcium Channel Blocker Exposure in Late Pregnancy and the Risk of Neonatal Seizures. Obstet Gynecol 126:271-8
Bateman, Brian T; Huybrechts, Krista F; Fischer, Michael A et al. (2015) Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study. Am J Obstet Gynecol 212:337.e1-14
Bateman, Brian T; Hernandez-Diaz, Sonia; Fischer, Michael A et al. (2015) Statins and congenital malformations: cohort study. BMJ 350:h1035
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
Saxena, A R; Chamarthi, B; Williams, G H et al. (2014) Predictors of plasma and urinary catecholamine levels in normotensive and hypertensive men and women. J Hum Hypertens 28:292-7
Nicklas, Jacinda M; Zera, Chloe A; England, Lucinda J et al. (2014) A web-based lifestyle intervention for women with recent gestational diabetes mellitus: a randomized controlled trial. Obstet Gynecol 124:563-70

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