The findings were published Feb. 26 in Nature Medicine.
The researchers found 35 genetic changes related to endothelial cell function, which has been associated with a higher low-density lipoprotein cholesterol sensitivity.
This sensitivity may amplify an individual’s risk of cardiovascular events, according to Feb. 26 news release from the health system.
“Patients who are LDL-C sensitive have a much greater benefit from aggressive cholesterol-lowering therapies, creating an opportunity for personalized prevention plans,” Nicholas Marston, MD, a cardiologist at Boston-based Brigham and Women’s hospital and lead author of the study, said in the release.
Dr. Marston shared with Becker’s what effect the score could have on clinical care.
Editor’s note: Responses have been lightly edited for clarity and length.
Question: How does this new risk score differ from existing risk assessment tools for coronary artery disease, and what advantages does it offer for clinical decision-making?
Dr. Nicholas Marston: This polygenic risk score is an endothelial cell pathway-specific subset of the established coronary artery disease polygenic risk score. One key advantage of this pathway-specific score is that it provides a unique axis of risk (endothelial cell dysfunction) that is not currently captured clinically. Second, it identifies patients who are most sensitive to cholesterol and therefore benefit most from more aggressive lipid-lowering therapy.
Q: How could this insight change the way cardiologists approach cholesterol management and prevention plans?
NM: Despite a lot of progress in preventive cardiology, we are still not able to identify some very high-risk patients who have undetected disease and are at risk of heart attack at a young age. This results in waiting too long to initiate and intensify lipid lowering therapies. Incorporating polygenic risk assessment into clinical practice provides additive information that can elevate a clinically low-risk individual into a range where statins should be considered.
Beyond just being an additional risk marker, PRS can also be used to guide decisions related to lipid lowering therapy and determine how much it will reduce their risk of a cardiovascular event. This adds precision to the way we practice preventive cardiology, targeting therapies to those who will have the greatest benefit from them.
Q: What are the biggest barriers to widespread adoption, and how might they be overcome?
NM: The biggest barrier to widespread adoption is insurance coverage. Insurance covers genetic testing for monogenic mutations, such as familial hypercholesterolemia, but not polygenic variation. This leaves patients to pay $250 out of pocket and limits our ability to complete a comprehensive genetic evaluation. The key to getting insurance companies to cover the relatively low cost of these tests is to demonstrate that the results are actionable and improve patient outcomes. This study achieves both of these aims.
Read the full study here.
Editor’s note: This article was updated March 4, 2025 at 1:22 pm CST.