Author: Dr Fouad Bitar

This landmark study published in npj Cardiovascular Health showed that childhood polygenic risk score (PRS)-guided prevention for coronary artery disease (CAD) could enable earlier targeted intervention, reduce future cardiovascular events, and generate major long-term health and economic benefits. The study projected that early identification of high-risk children could prevent 72 CAD events per 10,000 children and achieve a return on investment (ROI) exceeding 3600%, supporting a shift toward genome-first, early-life preventive cardiology.

The editorial highlights that the PROACT study introduces a novel genome-first strategy using polygenic
risk scores (PRS) to identify individuals who appear low-risk by traditional calculators but frequently
harbor subclinical coronary artery disease. It argues that prevention must evolve beyond age-based risk
models toward earlier, causal-factor–guided intervention integrating genomics, imaging, and targeted
therapy. 

This Landmark JAMA 2026 PROACT trials showed that adults with high coronary artery disease (CAD)
polygenic risk scores but low clinical risk were prospectively identified from a biobank and evaluated
with coronary CT angiography, demonstrating that about half had previously undetected subclinical
plaque despite favorable cardiovascular health. These findings show the feasibility of genome-first
prevention strategies and suggest that polygenic risk–guided identification could enable earlier targeted
pharmacologic prevention in individuals overlooked by conventional risk models.