Coronary artery disease risk assessment might soon rely on genetic testing, following a UK Biobank analysis that suggests adding a CAD multi-gene risk score to conventional biomarkers significantly improves disease prediction and patient identification.
- Traditional CAD risk assessment uses biomarkers that fluctuate over time, while genetic scores capture inherited disease risk since birth.
- Currently, there are over one million genetic mutations that can lead to inherited CAD risk.
Examining genetic profiles, researchers followed 353k UK Biobank participants without baseline CAD for 11 years on average, and compared the predictive effects of adding a polygenic risk score (PRS) to a combo of three CV biomarkers (LDL-C, Lp(a), hs-CRP), finding substantial improvements…
- The predictive model’s discrimination significantly improved when CAD PRS was added to biomarkers (C-index: 0.739 vs. 0.754).
- The improvement was also similar when apoB replaced LDL-C (C-index: 0.740 vs. 0.754).
- Patients in the highest category for all three biomarkers showed 2x CAD risk (aHR: 2.15), but those also in the highest CAD PRS category faced nearly 4x higher risk (aHR: 3.71).
- CAD PRS alone showed stronger association than any single biomarker, with the highest PRS group facing 78% higher risk.
- Risk stratification also remained consistent across patient sex, suggesting universal applicability.
Since genetic risk is determined at birth and remains constant, using polygenic risk scores for CAD could enable early identification of high-risk patients before biomarker abnormalities even develop.
- Some institutions already use PRS in clinical risk assessment, but insurance coverage remains limited with tests costing $200-$250.
- It’s also worth noting that high genetic risk doesn’t doom a patient, since knowing earlier can enable preventive interventions before disease manifests.
The Takeaway
This study, like other genetic cardiology studies, reminds us that some people are at higher risk of heart disease no matter how they live their lives. The good news is, we have the technology to find out who these people are and with a disease like CAD, catching it sooner always leads to better outcomes.
