Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Ezgi Caliskan Guzelce, MD

Brigham and Women’s Hospital
Medicine/Endocrinology, Diabetes & Hypertension
Email: ecaliskanguzelce@bwh.harvard.edu

Abstract

Men have higher baseline levels of Aldosterone (ALDO) than women, but women have greater ALDO response to angiotensin II (Ang II) and greater salt sensitivity of blood pressure (SSBP). We hypothesize that the sex difference in ALDO is mainly driven by higher plasma renin activity (PRA)/Ang II levels in men compared to women. To assess this potential underlying mechanism for these observations, 732 individuals from HyperPATH dataset compared ALDO and PRA between men and women. Baseline ALDO levels were higher in men than women on both low and liberal salt diets (p=0.001, p<0.0001). Conversely, ALDO responses to Ang II infusion and upright posture were higher in women than men (p<0.0001, p<0.0001). Other potential ALDO secretagogues did not differ by sex. To determine the generalizability of the ALDO response to Ang II, renal plasma flow and systolic blood pressure were also higher in women than men (p=0.0032; p<0.0001, respectively). Endogenous Ang II levels were higher in men than women on low salt diet (p=0.03), while delta Ang II levels, the difference between baseline and Ang II stimulated values, were similar. Women had greater SSBP than men (p<0.0001), which was primarily secondary to a greater reduction in BP on the low salt diet rather than an increase in BP on a liberal salt diet. In summary, 1) higher PRA and endogenous Ang II levels resulted in higher ALDO levels in men than women; higher endogenous Ang II levels saturate its AT1 receptors more in men than women, resulting in less Ang II responsiveness in Ang II targeted organs in men compared to women. 2) SSBP is higher in women than men because their BP is significantly lower, potentially secondary to their reduced PRA-AngII-ALDO response to the stress of the low salt diet.

Agenda

3PM – Welcome Remarks
3:05PM – Keynote Address
3:45PM – Featured Short Talks
4:20PM – Lightning Talks
4:50PM – Closing Remarks

Keynote Speaker

Janine Austin Clayton, MD

Janine Austin Clayton, M.D., Associate Director for Research on Women’s Health and Director of the Office of Research on Women’s Health (ORWH) at the National Institutes of Health (NIH), is the architect of the NIH policy requiring scientists to consider sex as a biological variable across the research spectrum. This policy is part of NIH’s initiative to enhance reproducibility through rigor and transparency. As co-chair of the NIH Working Group on Women in Biomedical Careers with NIH Director Dr. Francis Collins, Dr. Clayton also leads NIH’s efforts to advance women in science careers.

Prior to joining the ORWH, Dr. Clayton was the Deputy Clinical Director of the National Eye Institute (NEI) for seven years. A board-certified ophthalmologist, Dr. Clayton’s research interests include autoimmune ocular diseases and the role of sex and gender in health and disease. She is the author of more than 120 scientific publications, journal articles, and book chapters.
Dr. Clayton, a native Washingtonian, received her undergraduate degree with honors from Johns Hopkins University and her medical degree from Howard University College of Medicine. She completed a residency in ophthalmology at the Medical College of Virginia. Dr. Clayton completed fellowship training in cornea and external disease at the Wilmer Eye Institute at Johns Hopkins Hospital and in uveitis and ocular immunology at NEI.

Dr. Clayton has received numerous awards, including the Senior Achievement Award from the Board of Trustees of the American Academy of Ophthalmology in 2008 and the European Uveitis Patient Interest Association Clinical Uveitis Research Award in 2010. She was selected as a 2010 Silver Fellow by the Association for Research in Vision and Ophthalmology. In 2015, she was awarded the American Medical Women’s Association Lila A. Wallis Women’s Health Award and the Wenger Award for Excellence in Public Service. Dr. Clayton was granted the Bernadine Healy Award for Visionary Leadership in Women’s Health in 2016. She was also selected as an honoree for the Woman’s Day Red Dress Awards and the American Medical Association’s Dr. Nathan Davis Awards for Outstanding Government Service in 2017.