Polygenic Risk Score for Coronary Artery Disease Across the Spectrum of Atherosclerotic Disease

Area of Science:

• Cardiovascular Medicine
• Genetics
• Epidemiology

Background:

• Polygenic risk scores (PRS) for coronary artery disease (CAD) are valuable for risk stratification.
• The differential utility of CAD PRS across the spectrum of atherosclerotic cardiovascular disease (ASCVD) remains unclear.

Purpose of the Study:

• To compare the association of a CAD PRS with incident coronary events in patients with established ASCVD, ASCVD without a prior event, and without overt ASCVD.

Main Methods:

• A genome-wide CAD PRS was used to categorize 59,905 participants from 6 multinational cardiovascular trials into low, intermediate, and high genetic risk groups.
• Participants were grouped by ASCVD status: with a prior ischemic event, ASCVD without an event, and without overt ASCVD.
• The primary endpoint was a composite of major coronary events, including death from coronary disease, myocardial infarction, or coronary revascularization.

Main Results:

• Major coronary events were more frequent in high and intermediate genetic risk groups compared to the low genetic risk group (HRs 2.06 and 1.57, respectively).
• The association between genetic risk and major coronary events was strongest in patients without overt ASCVD (HR 4.63 for high vs. low risk).
• The absolute risk difference for major coronary events between high and low genetic risk was comparable across all ASCVD categories, ranging from 5.0% to 7.0% at 3 years.

Conclusions:

• A CAD PRS is associated with incident major coronary events across all categories of ASCVD.
• While PRS demonstrate a stronger relative risk association in individuals without established ASCVD, the absolute risk increase is similar regardless of ASCVD status.