Eur J Prev Cardiol. 2026 Apr 15:zwag203. doi: 10.1093/eurjpc/zwag203. Online ahead of print.
ABSTRACT
AIM: A high polygenic score for coronary artery disease (PRSCAD) has been demonstrated to be a strong and independent predictor of atherosclerotic cardiovascular disease (ASCVD) in patients with familial hypercholesterolemia (FH). The objective was to investigate if the addition of a PRSCAD to the FH-Risk-Score enhances ASCVD risk prediction compared to the clinical score alone.
METHODS: Data from 3 independent cohorts of patients with FH have been analysed in this longitudinal study (n=1438). The FH-Risk-Score equation was used to calculate the baseline 10-year ASCVD risk. A high PRSCAD was defined as a score > 75th percentile. The performance of the Combined score was assessed using measures of discrimination (C statistics), calibration (predicted risk vs. observed risk), and reclassification (using a 10-year risk cutoff of 20%).
RESULTS: Overall, the event rate was nearly doubled in individuals having a high PRSCAD (15% vs. 9%, HR 1.77, 95% CI 1.20-2.61, P=0.004). This association was stronger in those with a genetic confirmation of FH (17% vs. 8%, HR 2.34, 95% CI 1.50-3.67, P=0.0002). The Combined score was associated with a marginally non-significant higher C-index than the FH-Risk-Score alone (0.746 to 0.750, P=0.60). The difference in C-index was significant in patients with a genetic confirmation of FH in the moderate FH-Risk-Score group (0.617 to 0.717, P=0.05).
CONCLUSION: Overall, the addition of polygenic information using PRSCAD percentiles to the FH-Risk-Score estimate did not significantly enhance ASCVD risk prediction in patients with FH. Replication efforts with larger number of individuals and incident cases are warranted.
PMID:41983333 | DOI:10.1093/eurjpc/zwag203
