Hypertension, antihypertensive treatment, and uterine fibroid diagnosis in an integrated healthcare system - PROJECT SUMMARY This proposed four-year plan will support Susanna Mitro, PhD, MPH, in her transition to becoming an independent investigator. Dr. Mitro’s long-term goal is to elucidate complex interrelationships between cardiovascular health and benign gynecologic disease over the life course, using advanced statistical methods in electronic health records data. Approximately 20-50% of women develop clinically significant uterine fibroids, which can cause severe symptoms including heavy bleeding, pain, and fatigue. There are few non-invasive, non-hormonal treatment options for fibroids, in part because the causes of fibroids are largely unknown. Preliminary evidence suggests a link between elevated blood pressure and fibroid development, with the renin- angiotensin system providing a potential mechanism, but additional prospective epidemiologic research is needed. The proposed research will clarify associations between blood pressure, antihypertensive medication use, and fibroid diagnosis, and will test renin-angiotensin system signaling as a potential mechanism linking blood pressure and fibroid development. Specifically, Dr. Mitro will use an electronic health record-based cohort of women aged 18-55 to: quantify prospective associations between blood pressure trajectories and hypertension onset with fibroid diagnosis (Aim 1); estimate the causal effect of angiotensin-converting enzyme inhibitor versus thiazide diuretic treatment on fibroid diagnosis, using target trial emulation methods (Aim 2); and develop and validate a clinical fibroid severity model, enabling a future focus on clinically significant fibroids beginning at diagnosis (Aim 3). Findings have strong potential to expand understanding of fibroid etiology, leading to new treatment or prevention strategies. The proposal includes mentored and applied training in 1) pharmacoepidemiology methods; 2) use of health systems data to study benign gynecologic disease; 3) women’s cardiovascular epidemiology; and 4) professional skills, including grant-writing and responsible conduct of research. Trainings include coursework, seminars, conferences, and one-on-one and group mentorship from an exceptional team with complementary clinical, biostatistical, and epidemiologic expertise. Dr. Mitro’s proposed research and training benefits greatly from access to the outstanding resources available at her institution, Kaiser Permanente Northern California, an integrated healthcare delivery system serving a diverse population of over 4 million members whose complete medical experiences are captured in the electronic health record. Dr. Mitro has a strong foundation of training in epidemiology and biostatistics and prior research experiences in cardiometabolic health and fibroid treatment effectiveness. This Career Development Award will equip her with the knowledge, skills, and preliminary data to develop competitive R01 proposals and to establish a successful research program focused on assessing longitudinal interrelationships between benign gynecologic disease and cardiovascular health, with long-term potential to clarify the development of both benign gynecologic disease and cardiovascular risk factors in women.
