Polygenic Risk Score Implementation and Stratification for Managing Blood Pressure

This parallel-arm, randomized clinical trial is designed to assess the change in SBP following BP PRS dissemination and genomic counseling. Investigators will enroll 300 young and middle-aged adults (age: 18-55 years; 50% females; 50% non-White) with HTN [stratified by race, sex, and SBP PRS group (high vs. low/intermediate)] and poor CVH [American Heart Association's (AHA) Life Essential 8 Score: 0-50]. Participants will be randomized to A) routine clinical care (N=150), or B) SBP PRS dissemination (regular care + SBP PRS delivery and genetic counseling; N=150). After obtaining informed consent, the eligible participants will undergo genotyping and computation of their genome-wide SBP PRS. The SBP PRS results will be available within 10-15 days of screening. Participants will then be randomized in a 1:1 manner [stratified by sex, racial/ethnic group (White vs. non-White), and SBP PRS (high vs. low/intermediate)] to either the SBP PRS dissemination arm or the routine care arm. Participants will undergo a comprehensive baseline health assessment, including measurement of key HBM constructs, using the recently developed Attitudes and Beliefs about the CVD (ABCD) Risk Questionnaire, a 26-item instrument validated in the clinical setting with four subscales: perceived risk of heart attack/stroke, perceived benefits and intentions to exercise, healthy eating intentions, and perceived benefits and intentions to reducing smoking. Investigators will also assess the perceived severity of CVD, perceived barriers to prevention behaviors, and self-efficacy to perform preventive behaviors using subscales previously assessed for content and face validity by an expert review panel and patient focus groups. Physical activity status and sleep duration (using 7-day Actigraphy), detailed dietary history [using the United States Department of Agriculture (USDA) Healthy Eating Index and collected through the validated Nutrition Coordinating Center Nutrition Data System for Research (NCC NDSR) dietary assessment tool], health-related quality of life [using 36-Item Short Form Survey (SF-36), and the Centers for Disease Control and Prevention (CDC) Health-Related Quality of Life-14 (HRQOL-14)], medication adherence using the Medication Adherence Rating Scale (MARS), 24-hour ambulatory blood pressure monitoring (ABPM), current health behaviors (smoking, alcohol, recreational drugs), and other cardiometabolic health parameters [lipid profile, hemoglobin A1c (HbA1c), body mass index (BMI), and body composition), and anxiety [using the Beck Anxiety Inventory (BAI)].

Inclusion criteria

• Age 18 to 55 years (inclusive) at the time of screening.
• Diagnosis of hypertension defined by 2017 ACC/AHA guidelines, as evidenced by Resting office systolic blood pressure (SBP) of 130-160 mm Hg or Resting office diastolic blood pressure (DBP) of 80-100 mm Hg or Current use of antihypertensive medication.
• Poor cardiovascular health, defined as Life's Essential 8 score <50.
• Willing and able to undergo 24-hour ambulatory blood pressure monitoring (ABPM) to confirm hypertension.
• Able to provide informed consent.

Exclusion criteria

• History of cardiovascular disease, including Myocardial infarction, Angina, Cardiac arrhythmia, Coronary heart disease, Heart failure, Stroke, or transient ischemic attack.
• Body mass index (BMI) <18.5 kg/m² or >45 kg/m².
• Baseline office SBP >160 mm Hg or DBP >100 mm Hg.
• Use of more than two antihypertensive medication classes.
• Not hypertensive based on 24-hour ABPM (per 2017 ACC/AHA criteria).
• Pregnant or breastfeeding.
• Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² (using CKD-EPI equation).
• Urine albumin-to-creatinine ratio ≥30 mg/g.
• Hepatic transaminase levels >3× the upper limit of normal.
• Significant psychiatric illness (assessed via Global Health Questionnaire-12).
• Moderate or severe anxiety (Beck Anxiety Inventory [BAI] score >16).