PROJECT SUMMARY/ABSTRACT Hypertension is the leading preventable risk factor for cardiovascular disease (CVD) and all-cause mortality, worldwide, and is a huge financial burden to society. Prevention and treatment of high blood pressure (BP), including stage 1 hypertension, is crucial for reducing the global burden of CVD. Previous randomized controlled trials have shown that potassium supplementation lowers BP. However, these trials only compared the efficacy of a single dosage of potassium supplementation (mostly 60 mmol/day) compared with placebo on BP. The lack of intake-response evidence between potassium supplementation and BP has resulted in an inability to establish the optimal level of potassium intake for hypertension prevention and treatment. The objective of this trial is to evaluate the intake-response relationship between potassium supplementation and BP in adults with stage 1 hypertension. The primary outcome will be the difference in systolic BP from baseline to 12-week follow-up among randomized groups. Secondary outcomes will include diastolic BP; 24-hour and nighttime systolic and diastolic BP; and other CVD risk factors. The consistency of treatment effects by age, sex, race, central adiposity, and baseline dietary sodium and potassium intake will be evaluated. This will be a randomized, double-blind, placebo-controlled, intake-response trial with a 4-arm, parallel design. Using a stratified, blocked randomization scheme, eligible participants will be assigned to placebo or 1 of 3 potassium supplementation arms in which 0, 30, 60, or 90 mmol/day (0, 1173, 2346, or 3519 mg/day) of additional potassium will be administered orally for 12 weeks. The study participants, investigators, and clinical staff who collect the study data will be blinded to intervention assignments. This trial has >90% statistical power to detect an intake-response relationship between potassium supplementation and BP, assuming each additional 30 mmol/day (1173 mg/day) potassium decreases systolic BP by an additional 2 mm Hg over 12 weeks, beyond placebo. We will recruit 208 study participants (n=52 in each group) with stage 1 hypertension (untreated systolic BP 130-139 and diastolic BP <90 mm Hg) from the greater New Orleans metropolitan area. Eligible participants will be randomized to treatment with placebo or 1 of 3 potassium supplementation interventions for 12 weeks. BP and other cardiometabolic risk factors will be measured at baseline, 6, and 12 weeks of follow- up. Difference in baseline to 12-week systolic BP across the treatment arms will be compared per intention-to- treat analysis. This study is novel because it is the first randomized controlled trial to test the intake-response effects of potassium supplementation on BP in humans. The study has important clinical and public health significance because it will identify the optimal level of potassium supplementation for BP lowering among adults with stage 1 hypertension. This information can be...