Impact of Disclosing Coronary Artery Disease Polygenic Risk Score on Cardiovascular Health (PROACT 3)

Mass General Brigham

Status: Enrolling

Conditions: Coronary Artery Disease

Treatments: Behavioral: Deferred Disclosure of non-high CAD PRS; Behavioral: Immediate disclosure of non-high CAD PRS

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07087431

2025P001499

R01HL164629 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The goal of this clinical trial is to evaluate whether disclosure of a non-high polygenic risk score for coronary artery disease (CAD PRS) is non-inferior to standard of care in maintaining cardiovascular health over one year among adults aged 40-75 years without cardiovascular disease and not on statins.

Full description

The main question PROACT 3 aims to answer is whether disclosure of a non-high CAD PRS result influences cardiovascular health behaviors and outcomes.

This is a single-center, randomized, non-inferiority trial of 400 adults aged 40-75 without cardiovascular disease and not on statins, identified through the Mass General Brigham primary care network. All participants will undergo CAD PRS testing, and those with non-high genetic risk will be randomized in a 1:1 ratio to receive immediate disclosure of their results or deferred disclosure after 12 months. The primary outcome is the change in cardiovascular health as measured by the American Heart Association's Life's Essential 8 (LE8) score from baseline to 12 months.

Secondary outcomes include engagement with preventive care, such as completion of lipid panels and blood pressure measurements, attendance at primary care visits, and initiation of preventive therapies (antihypertensive, lipid-lowering, or GLP-1 receptor agonist therapy or other anti-diabetic therapy) when clinically indicated. Additional outcomes will include changes in individual LE8 behavioral components (physical activity, diet, tobacco use, and sleep) and BMI from baseline to 12 months.

This trial is designed to address concerns about potential false reassurance from non-high CAD PRS disclosure and will provide empirical evidence to guide best practices for polygenic risk communication in preventive cardiology.

Enrollment: 400 estimated patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Current age 40-75 years
• Established primary care at Mass General Brigham with at least one visit in the last 2 years

Exclusion criteria

• High CAD PRS
• Known cardiovascular disease, defined by a diagnosis of coronary artery disease, peripheral artery disease, or cerebrovascular disease
• Currently taking LDL cholesterol- lowering or anti-inflammatory medications, including statins or colchicine
• Liver disease (cirrhosis, active hepatitis, ALT > 3x ULN, total bilirubin > 2x ULN and not Gilbert's Syndrome)
• Contraindication to taking colchicine or rosuvastatin (allergy, liver or kidney disease)
• Pregnancy, breastfeeding, or planning to become pregnant during the study period
• Inability to provide informed consent
• Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m²
• BMI ≥ 40 kg/m²
• Inability to hold breath for 10 seconds

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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400 participants in 2 patient groups

Immediate Disclosure

Experimental group

Description:

Participants are randomized to receive their non-high CAD PRS immediately after genotyping.

Treatment:

Behavioral: Immediate disclosure of non-high CAD PRS

Deferred Disclosure

Active Comparator group

Description:

Participants are randomized to have their non-high CAD PRS withheld for 12 months before receiving their result after the follow up period.

Treatment:

Behavioral: Deferred Disclosure of non-high CAD PRS