PROJECT ABSTRACT Elevated blood pressure (BP), including hypertension (HTN) and preHTN, affects 2 in 3 American adults and is a major contributor to cardiovascular disease (CVD) morbidity, mortality, and healthcare costs. Despite widespread use of pharmacotherapy, only about half of HTN is controlled, highlighting a need for innovative strategies to decrease the burden of elevated BP. Though regular exercise in the form of moderate-to-vigorous physical activity (MVPA) occurring in bouts of at least 10 minutes is recommended to decrease BP, we propose that reducing time spent sitting or `sedentary behavior' (SED) is a distinct, novel strategy that could lower BP in individuals with preHTN and HTN. Recent occupational and leisure changes (e.g., computers, video streaming) have resulted in more than half of the American day being spent in SED. At the same time, many observational studies have linked excessive SED with adverse outcomes, including HTN and CVD. Moreover, same day laboratory studies suggest that reducing or interrupting SED decreases BP acutely and our preliminary data suggest that systolic BP (SBP) is reduced by 4-6 mmHg after a 12-week SED intervention. Yet, there have been no robust, randomized trials of sufficient size and duration to demonstrate that reducing SED has sustained benefits on BP. Before clinical or public health SED recommendations can be made, such experimental evidence is imperative. Thus, the goal of this application is to demonstrate the efficacy of SED reduction to decrease BP in a 3-month randomized, clinical trial (intervention vs. control) in 300 adults (150 per group) with pre-to-Stage I HTN who have structured, prolonged SED as desk workers. We will use our proven approach that intervenes on multiple levels (individual, environmental modification with a sit-stand desk attachment) and utilizes behavioral strategies (individual counseling, self-monitoring, external prompting with a wrist-worn monitor light-intensity physical activity (LPA) (standing, light movement) and short spurts (<10 min) of activity (sporadic MVPA) as replacement behaviors. We will comprehensively study the effects of our intervention on vascular health by assessing resting BP, ambulatory BP, and carotid-femoral pulse wave velocity (cfPWV) (Aim 1) and key potential mechanisms (plasma renin activity, aldosterone) (Aim 2). We will use objective activity monitoring to evaluate dose-response relationships between amount of achieved SED reduction (and resulting increases in LPA and sporadic MVPA) with changes in outcomes (Aim 3). We will also study adiposity, fitness, and insulin sensitivity as exploratory outcomes that could change with our intervention, and if so, might relate to BP. Results from this study will determine whether decreasing SED can improve BP and vascular health and inform the necessary dose of SED reduction for clinically meaningful benefits. Also, evaluation of our novel intervention approach will inform future intervention...