Polygenic Risk Score Implementation and Stratification for Managing Blood Pressure

NCT06962488 | Recruiting DMC

• 2 other identifiers: IRB-300014760R01HL176882
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

In a multi-ethnic population, a genome-wide polygenic risk score (PRS) for systolic blood pressure (SBP), incorporating over one million common genetic variants, predicts blood pressure (BP) traits and the risk of adverse cardiovascular events beyond traditional risk factors. Delivering SBP PRS information to young and middle-aged adults with hypertension (HTN) and poor cardiovascular health (CVH) may enhance their motivation to adopt healthier lifestyles, improve blood pressure control, and ultimately reduce the risk of future cardiovascular disease (CVD). This randomized controlled trial will assess the impact of SBP PRS disclosure and theory-based genomic counseling on systolic blood pressure and health behaviors. A total of 300 adults aged 18-55 years will be enrolled and randomized to receive either routine clinical care or SBP PRS results with structured genomic counseling based on the Health Belief Model (HBM). Participants will be followed for 12 months. The primary outcome is change in 24-hour mean SBP from baseline to one year. Secondary outcomes include changes in physical activity, diet, medication adherence, smoking, lipid and glucose levels, and body composition. The study will also evaluate how behavior change is influenced by health beliefs, including perceived risk and self-efficacy. This study aims to advance the use of genomic tools in hypertension management and cardiovascular disease prevention.

Conditions

Hypertension; Atherosclerotic Cardiovascular Disease

Keywords

Systolic Blood Pressure; Polygenic Risk Score; Genomic Counseling; Health Belief Model; Cardiovascular Health

Outcome Measures

Primary Outcomes (1)

• Change in Mean 24-Hour Systolic Blood Pressure

  The difference in the 24-hour mean systolic BP between the two study groups at 1 year, adjusted for baseline.

  1 year

Secondary Outcomes (14)

• Change in Physical Activity Levels

  1 year

• Change in Healthy Diet Index Score

  1 year

• Change in Medication Adherence

  1 year

• Change in Ambulatory Blood Pressure Parameters

  1 year

• Change in Lipid Profile

  1 year

Study Arms (2)

SBP PRS Dissemination

EXPERIMENTAL

Participants randomized to this arm will receive their personalized SBP polygenic risk score (PRS), along with structured genomic counseling sessions guided by the Health Belief Model and routine clinical care. Counseling will be delivered by trained genetic counselors at baseline and during 3-monthly in-person follow-up visits. The counseling is designed to increase perceived susceptibility, reduce perceived barriers, and improve self-efficacy for health behavior change.

Behavioral: SBP PRS Dissemination

Routine Clinical Care

ACTIVE COMPARATOR

Participants randomized to this arm will receive standard clinical care for hypertension, including educational materials on blood pressure control, lifestyle modification, and cardiovascular health. These materials will be adapted from the American Heart Association Life's Essential 8 and the ACC preventive cardiology toolkit. Participants will not receive SBP PRS results or genomic counseling during the study. At the end-of-study visit (12 months), participants in this group will be offered their SBP PRS results and optional genomic counseling.

Behavioral: Regular Care

Interventions

Regular Care BEHAVIORAL

Educational brochures and lifestyle guidance on blood pressure control, medication adherence, physical activity, and healthy diet, provided at baseline only. No additional counseling or genetic risk disclosure will occur during the 12-month intervention period.

Routine Clinical Care

SBP PRS Dissemination BEHAVIORAL

Participants receive individualized SBP PRS reports and structured genomic counseling sessions delivered by trained genetic counselors. Counseling addresses key constructs of the Health Belief Model, including perceived susceptibility, severity, and benefits of behavior change, with an emphasis on lifestyle modification and medication adherence.

SBP PRS Dissemination

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Related Publications (2)

• Shetty NS, Pampana A, Patel N, Yerabolu K, Patel G, Irvin MR, Natarajan P, Lin HJ, Guo X, Rich SS, Rotter JI, Li P, Arora G, Arora P. Sex Differences in the Association of Multiethnic Genome-Wide Blood Pressure Polygenic Risk Score With Population-Level Systolic Blood Pressure Trajectories. Circ Genom Precis Med. 2024 Apr;17(2):e004515. doi: 10.1161/CIRCGEN.123.004515. Epub 2024 Feb 19. No abstract available.

  PMID: 38372177 BACKGROUND

• Shetty NS, Pampana A, Patel N, Li P, Yerabolu K, Gaonkar M, Arora G, Arora P. Sex Differences in the Association of Genome-Wide Systolic Blood Pressure Polygenic Risk Score With Hypertension. Circ Genom Precis Med. 2023 Dec;16(6):e004259. doi: 10.1161/CIRCGEN.123.004259. Epub 2023 Oct 9. No abstract available.

  PMID: 37807951 BACKGROUND

MeSH Terms

Conditions

Hypertension; Atherosclerosis; Genetic Risk Score

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Genetic Predisposition to Disease; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Pankaj Arora, MD, FAHA

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nehal Vekariya, MS

CONTACT

2059347173; nvekariya@uabmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Division of Cardiovasular Disease, Department of Medicine

Study Record Dates

• First Submitted: April 21, 2025
• First Posted: May 8, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): July 31, 2030
• Last Updated: September 3, 2025

Record last verified: 2025-09

Locations

US (1)