PROJECT SUMMARY/ABSTRACT Post traumatic stress disorder (PTSD) is linked to accelerated aging and is associated with increased risk of early-onset cardiovascular disease (CVD) in both men and women. PTSD is associated with premature vascular aging (i.e., large elastic arterial stiffening and vascular endothelial dysfunction) and autonomic dysfunction (e.g., reduced cardiovagal baroreflex sensitivity [cBRS] and heart rate variability [HRV]), key antecedents in the development of CVD. Sleep is important for cardiovascular health via cellular and tissue repair, free radical detoxification and reducing oxidative stress and inflammation. Nightmares, a central feature of PTSD, are a debilitating condition that can lead to sleep deprivation or insomnia, daytime sleepiness and other sequala, that ultimately causes clinically significant distress and impairment in social, occupational and cardiovascular function. As such, therapeutic strategies and interventions that address nightmare-associated sleep disturbances in individuals with PTSD is clinically important for improving sleep quality, cardiovascular health and risk for future age-associated CVD. NightWare™ digital therapeutic system is a novel smart watch application that was recently granted Breakthrough Device designation by the FDA for the treatment of nightmares in adults with PTSD. It uses machine learning to detect, track and arouse an individual out of a nightmare by sending vibrotactile feedback to a smart watch, and arousing the individual out of the nightmare without awakening and disrupting sleep. In the present R21 we are proposing a randomized, double-blind, placebo (i.e., sham intervention) controlled parallel pilot study that will provide the first clinical evidence for the efficacy of the NightWare digital therapeutic system to improve cardiovascular health outcomes in adults with nightmares associated with PTSD. An additional goal of this R21 will be to obtain exploratory mechanistic insight by which NightWare improves cardiovascular function, specifically, related to sleep quality, nitric oxide bioavailability, free radical production, oxidative stress and inflammation. We hypothesize that 6 weeks of the NightWare intervention will improve outcomes of vascular aging (e.g., large elastic arterial stiffening, vascular endothelial dysfunction) and autonomic function (cBRS, HRV) in adults with PTSD-related nightmares. The results from this pilot investigation will provide the basis for a larger randomized clinical trial that would be conducted to establish the efficacy of NightWare as a safe and effective therapeutic strategy for treating nightmares, promoting healthy vascular aging, autonomic function and reducing the risk for CVD later in life in adults with nightmares associated with PTSD.