Longitudinal changes in vascular and autonomic function in premenopausal women with PTSD

Project Summary The ultimate objective of this R03 proposal is to enable Dr. Ida Fonkoue to launch her independent research career by 1) expanding her current K01 research objectives; 2) providing additional support in her transition to a future NIH R01 grant; and 3) generating sufficient preliminary results to support that R01 application. The

candidate’s long-term goal is to build an NIH-funded research program in clinical and translational research in women’s health, studying longitudinal derangements of vascular, neural and hormonal control, that contribute to the high rates of hypertension and cardiovascular disease (CVD) in women living with chronic stress

exposure such as those with post-traumatic stress disorder (PTSD), generalized anxiety disorder or panic disorder. Over 7 million U.S. adults have PTSD, a disorder associated with a greater risk for hypertension and CVD. While healthy premenopausal women are relatively protected from CVD compared to men, a diagnosis

of PTSD increases CVD risk in women by up to 3-fold. According to the Centers for Disease Control and Prevention, over 60 million women in the United States are living with some form of heart disease. Understanding the mechanisms underlying long-term CVD risk in women with PTSD is of paramount importance to develop intervention strategies aiming at protecting the future health of this vulnerable

population. Based on our preliminary data, the working hypothesis of this project is that: Over time, PTSD significantly inhibits nitric oxide bioavailability, resulting in accelerated autonomic and vascular dysfunctions in premenopausal women; and that these changes are exacerbated by low estradiol (E2) levels and sleep

disturbances. Aim 1 will measure longitudinal alterations in sympathetic nervous system (SNS) activity in premenopausal women with PTSD and determine the extent to which these alterations are a function of low E2 levels and low sleep efficiency at two years follow-up. Aim 2 will measure longitudinal alterations in vascular

function in premenopausal women with PTSD and determine the extent to which these alterations are a function of low E2 levels and low sleep efficiency at two years follow-up. We will use gold-standard in vivo measures of sympathetic nerve activity (microneurography), endothelial (FMD) and vascular (applanation

tonometry) function to study young, traumatized women with and without PTSD. The university of Minnesota University, where the project will be completed, boasts an intellectually rich research environment whose resources will be used to carry out the proposed research, including an NIH-funded Clinical and Translational

Science Institute (CTSI). During this R03 award, the PI will devote 75% effort to this project and her current K01 project. She recently achieved an important career-development milestone for her transition to full independence by completing her Master of Science in Clinical Research. This research project, combined with

findings from her K01 and ongoing multidisciplinary mentorship, will help Dr. Fonkoue launch and sustain a meritorious R01-funded independent research program.