Polygenic Risk Based Detection and Treatment of Subclinical Coronary Atherosclerosis in the PROACT Clinical Trials
Authors' conclusion
These exploratory findings highlight the feasibility of implementing genotype-first recruitment for prevention trials and reveal a large proportion of "silent" high-genetic risk individuals with subclinical plaque for whom pharmacotherapy could be beneficial but who remain undetected by standard clinical assessments.
Study context
- Population
- Adults 40 to 75 years with high coronary artery disease (CAD) polygenic risk scores (PRS), without CVD, not on lipid-lowering therapy, in a hospital-based biobankgenotyped
- Participants
- 64,092 adults
- Outcome
- Eligibility yield, callback engagement, and subclinical coronary atherosclerosis on coronary CT angiography
Methodological detailsgenotype-first, biobank-enabled, hospital-based biobank
- Genotype-first
- Biobank-enabled
- Hospital-based biobank
Main finding
As reported in the abstract
Eligibility, callback engagement and subclinical plaque
- Eligible with high CAD PRS among genotyped
- 2,495 (3.9%)
- Median 10-year pooled cohort equations ASCVD risk among eligible (Q1-Q3: 1%-8%)
- 3%
- Opted in among 1,314 invited
- 283 (21.5%)
- Completed baseline imaging among 1,314 invited
- 204 (15.5%)
- Subclinical plaque among first 204 participants
- 102 of 204
Further findings
Subclinical plaque prevalence by sex
- Men
- 76.2%
- Women
- 38.3%
- High across age groups
Characteristics of opt-in vs non-opt-in
- Those who opted in had higher specialty care engagement and lived closer to the study site
Life's Essential 8 score in first 204 participants
- Mean Life's Essential 8 score (± 11.5), vs US average of ∼65
- 73.3
- Mean age 56.3 ± 8.5 years, 69% women
Original publication
Polygenic Risk Based Detection and Treatment of Subclinical Coronary Atherosclerosis in the PROACT Clinical Trials. J Am Coll Cardiol. Published 18 February 2026. doi:10.
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