Can a Genetic Scorecard Prevent Heart Disease Before It Starts?

SAN FRANCISCO, CA – April 07, 2026 – A groundbreaking clinical trial is underway to answer a critical question in modern medicine: if you knew your genetic risk for heart disease, would you change your life to prevent it? In a significant step toward personalized preventive care, genetics firm Allelica has partnered with Mass General Brigham to launch the PROACT 3 clinical trial, which will evaluate how disclosing a person's inherited risk for coronary artery disease (CAD) influences their health choices and clinical outcomes.

The study, led by Dr. Akl Fahed of Massachusetts General Hospital and Harvard Medical School, utilizes Allelica's advanced multi-ancestry polygenic risk score (PRS) to arm patients with knowledge that has, until now, been hidden within their DNA. The trial aims to provide definitive evidence on whether genetic insights can be a powerful catalyst for proactive health management.

The Search for 'Silent' Risk

Coronary artery disease remains the leading cause of death globally, claiming nearly 18 million lives annually according to the World Health Organization. In the United States alone, the Centers for Disease Control and Prevention reports that one person dies from cardiovascular disease every 33 seconds. A major challenge in combating this epidemic is its insidious nature; many individuals harbor significant underlying atherosclerosis—the buildup of plaque in arteries—with no outward symptoms until a catastrophic event like a heart attack occurs.

For decades, clinicians have relied on a standard set of tools to predict risk: cholesterol levels, blood pressure, smoking status, and family history. These are aggregated into risk calculators, like the Pooled Cohort Equations, to estimate a person's 10-year chance of a cardiovascular event. While useful, these methods are imperfect and can miss a substantial "silent" population at high risk.

This is where polygenic risk scores enter the picture. A PRS analyzes thousands, or even millions, of tiny genetic variations across a person's genome to calculate their inherited predisposition to a specific disease. The PROACT trial series at Mass General Brigham has been at the forefront of exploring this technology's potential. The preceding NIH-funded PROACT 1 and 2 trials have already yielded startling findings. Interim results revealed that nearly 4% of participants with a low clinical risk score actually carried a high polygenic risk for CAD. More critically, among this group, half were found to have subclinical plaque already forming in their arteries, a silent harbinger of future disease.

These early trials established that PRS can effectively identify a hidden-risk population that traditional screening overlooks. PROACT 2 is currently investigating whether drug interventions can slow plaque progression in this genetically vulnerable group. PROACT 3 takes the next logical and crucial step: moving from detection to real-world application in a primary care setting.

A Test for the Real World

The PROACT 3 trial is designed to test the real-world impact of genetic disclosure. The study will enroll 500 adults without a history of cardiovascular disease and not currently taking cholesterol-lowering medications. All participants will have their CAD polygenic risk calculated using Allelica's test. They will then be randomized into two groups: one will receive their genetic risk score immediately, while the other will receive it after a 12-month delay.

Researchers will track changes in key health metrics, most notably LDL ("bad") cholesterol levels, as well as shifts in cardiovascular health behaviors like diet, exercise, and engagement with their healthcare providers. The central question is whether the act of learning one's genetic risk provides a strong enough motivation to trigger meaningful, measurable lifestyle and clinical changes.

"Allelica is proud to support Dr. Fahed and his team as they expand the evidence of clinical utility of CAD polygenic risk score testing in cardiovascular prevention," said Dr. Giordano Botta, CEO & Co-Founder of Allelica, in a statement. "The objective of the PROACT 3 study is closely aligned with our company's mission to empower healthcare providers with safe diagnostics that improve patient care and ultimately save lives."

The trial's leadership under Dr. Akl Fahed, a respected researcher at Massachusetts General Hospital, Harvard Medical School, and the Broad Institute of MIT and Harvard, lends significant weight to the study. His work focuses specifically on using genomics and advanced imaging to proactively identify and manage individuals at high risk for CAD, making him an ideal leader for this pivotal investigation.

Bridging the Genomic Divide

A critical and differentiating feature of the PROACT 3 trial is its use of Allelica's multi-ancestry PRS. This directly confronts one of the most significant challenges in modern genomics: a profound lack of diversity in the data used to build predictive tools. Historically, the vast majority of genomic research has been conducted on individuals of European descent. As a result, many genetic tests, including early-generation PRS, are significantly less accurate for people of African, Asian, or Hispanic ancestry.

This "ancestry gap" risks creating a new frontier of health inequity, where the benefits of precision medicine are not accessible to all populations. An inaccurate risk score could provide false reassurance to a high-risk individual or cause undue alarm for someone at low risk, leading to mismanaged care.

Allelica has positioned itself as a leader in solving this problem. The company's multi-ancestry CAD PRS, validated in a late 2023 Nature Communications publication, was specifically developed and trained on diverse datasets to ensure its accuracy across different populations. By incorporating this technology, the PROACT 3 trial is not only testing the behavioral impact of genetic disclosure but is also doing so with a tool designed for equitable application. This commitment ensures that the findings will be more generalizable and that the future of preventive genomics is built on a foundation of inclusivity.

From Lab to Clinic: The Future of Preventive Cardiology

The implications of the PROACT 3 trial extend far beyond the 500 participants. If the results demonstrate that disclosing genetic risk leads to improved health outcomes, it could provide the robust evidence needed for medical societies to incorporate PRS into standard clinical guidelines for cardiovascular prevention.

Such a shift would represent a paradigm change in cardiology, moving from a reactive model—treating disease after it appears—to a truly proactive one. Instead of waiting for a patient to develop high cholesterol or hypertension in their 40s or 50s, a physician could use a one-time genetic test early in adulthood to identify high-risk individuals. This would enable decades of targeted prevention, including personalized lifestyle counseling and earlier consideration of therapies like statins, potentially averting heart attacks before the underlying disease can take hold.

For Allelica, the partnership with a world-class institution like Mass General Brigham is a powerful validation of its technology and strategic focus. By prioritizing rigorous clinical utility studies and addressing the critical issue of health equity, the company is carving out a leadership position in the burgeoning market for advanced diagnostics. The results of PROACT 3 will be closely watched by clinicians, public health officials, and the healthcare industry, as they hold the potential to unlock a new, more personalized era in the fight against heart disease.