Enhanced Risk Prediction for Coronary Heart Disease by Leveraging Polygenic Risk Score and Clinical Risk Score in European Hypertensive Adults

Background: Coronary heart disease (CHD) is the leading cause of premature mortality. The incremental value of a polygenic risk score (PRS) to a clinical risk score towards improving CHD prediction is controversial. Meanwhile, the effect of PRSs on CHD prediction in the chronic disease population is unclear. Methods: Utilizing publicly available summary statistical data, we developed several PRSs using the genome data of European ancestry from the Atherosclerosis Risk in Communities Study. Furthermore, we investigated the association of CHD with the best-performing PRS in both the overall and chronic disease cohorts. Additionally, we evaluated whether adding the best-performing PRS to the clinical risk score improves risk prediction. Results: A total of 6152 subjects (767 CHD cases) were included in this study. The high values from the developed best-performing PRS were significantly associated with an increased risk of CHD, with a stronger association in the hypertensive population (interaction p = 0.0144). Compared with individuals in the bottom 20% of the PRS values, those in the top 20% were more than 3-fold more likely to develop CHD in the overall cohort, rising to 5-fold in the hypertensive cohort. Adding PRS to the clinical risk score significantly improved the C-index (0.72 to 0.74; p = 0.004), with a 10% net reclassification improvement overall. The hypertensive population showed the greatest improvements. Furthermore, we observed a significant gradient of 10-year and lifetime risk of CHD based on the PRS within each clinical risk category. Conclusions: Compared to the clinical risk score, integrating the PRS significantly improved CHD prediction and better identified CHD risk trajectories, especially in the European hypertensive adult population.