Clinical trial NCT06962488: Clinical Implementation of Blood Pressure Polygenic Risk Score
Official title: Clinical Implementation of Blood Pressure Polygenic Risk Score
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Hypertension
Atherosclerotic Cardiovascular Disease
Keywords: Systolic Blood Pressure
Polygenic Risk Score
Genomic Counseling
Health Belief Model
Cardiovascular Health
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2025-05-08
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: 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 \[using the Beck Anxiety Inventory (BAI)\].

Eligibility criteria: 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).

Primary outcomes:
measure: Change in Mean 24-Hour Systolic Blood Pressure
timeFrame: 1 year
Secondary outcomes:
measure: Change in Physical Activity Levels
timeFrame: 1 year
measure: Change in Healthy Diet Index Score
timeFrame: 1 year
measure: Change in Medication Adherence
timeFrame: 1 year
measure: Change in Ambulatory Blood Pressure Parameters
timeFrame: 1 year
measure: Change in Lipid Profile
timeFrame: 1 year
measure: Change in Sleep Duration
timeFrame: 1 year
measure: Change in Body Mass Index
timeFrame: 1 year
measure: Change in Fat Mass
timeFrame: 1 year
measure: Change in Lean Mass
timeFrame: 1 year
measure: Change in Health Belief Model Constructs
timeFrame: 1 year
measure: Change in Smoking Behavior
timeFrame: 1 year
measure: Change in Health-Related Quality of Life (SF-36)
timeFrame: 1 year
measure: Change in Health-Related Quality of Life (CDC HRQOL-14)
timeFrame: 1 year
measure: Change in Anxiety
timeFrame: 1 year
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Pankaj Arora, MD, FAHA
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.