European and US Guideline-Based Statin Eligibility, Genetically Predicted Coronary Artery Disease, and the Risk of...

Area of Science:

• Cardiology
• Genetics
• Preventive Medicine

Background:

• Established clinical risk scores are used for primary prevention of coronary artery disease (CAD).
• The utility of polygenic risk scores in guiding treatment decisions requires further investigation.

Purpose of the Study:

• To assess if the coronary artery disease polygenic risk score (CAD-PRS) can improve guidance for initiating or deferring lipid-lowering treatment beyond current clinical risk scores.
• To evaluate CAD-PRS's effectiveness across different patient groups based on statin indication.

Main Methods:

• Analysis of 311,799 UK Biobank participants without prior atherosclerotic cardiovascular disease, diabetes, or lipid-lowering treatment.
• Categorization of participants into statin indicated, unclear, or not indicated groups based on European and US guidelines.
• Longitudinal follow-up for major coronary events and assessment of CAD-PRS performance with established risk scores (European-SCORE2, US-PCE).

Main Results:

• CAD-PRS identified individuals within unclear and indicated groups who had higher or lower risks compared to average.
• The addition of CAD-PRS to European-SCORE2 and US-PCE improved risk reclassification, particularly in statin-indicated and statin-indication-unclear groups.
• CAD-PRS demonstrated improved C-statistics for major coronary and atherosclerotic cardiovascular disease events in these groups, with minimal impact in the statin-not-indicated group.

Conclusions:

• CAD-PRS can effectively guide statin initiation and deferral decisions for individuals with unclear or indicated statin use.
• The clinical utility of CAD-PRS is limited in individuals not indicated for statin therapy.