Polygenic Risk Score
AI search August 2025 version 1
For a cardiologist, the use of Polygenic Risk Scores (PRS) for coronary artery disease (CAD) has evolved significantly in recent years. The focus has shifted from mere research validation to exploring its practical clinical utility, particularly in reclassifying risk in intermediate-risk patients and in identifying individuals at high genetic risk who may benefit from early and aggressive preventive therapies.
A key figure in this field is Dr. Amit V. Khera, and his work, along with that of his colleagues, has been instrumental in advancing the clinical application of PRS.
Latest on PRS for CAD
The latest research on PRS for CAD focuses on several key areas:
Risk Reclassification: One of the most promising applications of PRS is its ability to reclassify risk, particularly in patients with borderline or intermediate risk according to traditional risk calculators like the Pooled Cohort Equations (PCE) or SCORE2. Studies show that adding a PRS to these models can significantly improve risk prediction and help identify individuals who might benefit from statin therapy or other intensive preventive measures, even if their traditional risk factors don't meet guideline thresholds.
Reference: A study in the European Heart Journal found that adding a PRS to a clinical risk score can improve the identification of individuals at increased risk in a real-world clinical setting. Reference: Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting
Outperforming Traditional Family History: PRS is emerging as a more powerful and objective measure of genetic risk than a self-reported family history. While family history is a well-established risk factor, a high PRS can identify individuals with a high genetic risk even in the absence of a documented family history, and it has been shown to be a better stratifier of risk.
Reference: A study published on UK Biobank data highlights that PRS can stratify CAD risk more effectively than family history alone, particularly among subjects with borderline/intermediate ASCVD risk. Reference: The Science Behind Polygenic Risk Scores - Coronary Artery Disease (CAD)
Prediction in Young Individuals: Traditional risk scores are limited in younger individuals because age is the single most important determinant of 10-year risk. A high PRS can identify young people with a high lifetime risk of CAD, allowing for earlier and more targeted preventive interventions. This addresses a major gap in current prevention strategies, which often delay risk assessment until middle age.
Clinical Implementation and Guidelines
The clinical community is actively working on a framework for the responsible use of PRS. While not yet universally integrated into standard care, several consensus statements and reports have laid out a roadmap for its future adoption:
ESC Consensus Statement: The European Society of Cardiology has released a clinical consensus statement on the utility and implementation of PRS for cardiovascular disease. The document acknowledges the promise of PRS as a risk modifier but also highlights the need for further evidence on its clinical utility and a clear framework for its integration into routine care.
Reference: Clinical utility and implementation of polygenic risk scores for predicting cardiovascular disease: A clinical consensus statement
AHA Scientific Statement: The American Heart Association has also published a scientific statement on PRS for cardiovascular disease, outlining what they are, how they are developed and validated, and the opportunities and challenges for their use in clinical practice.
Reference: Polygenic Risk Scores for Cardiovascular Disease: A Scientific Statement From the American Heart Association