AI Article Synopsis
- Interest in targeted screening for atrial fibrillation (AF) is rising, but the impact of genetics on identifying at-risk patients is still uncertain.
- A study involving over 36,000 participants revealed that a polygenic risk score (PRS) significantly predicts AF risk, with those in the top 20% of PRS being more than twice as likely to develop AF compared to those in the bottom 20%.
- The PRS enhances risk stratification beyond traditional clinical models, increasing prediction accuracy of AF events when combined with other factors like NT-proBNP.
Article Abstract
Aims: Interest in targeted screening programmes for atrial fibrillation (AF) has increased, yet the role of genetics in identifying patients at highest risk of developing AF is unclear.
Methods And Results: A total of 36,662 subjects without prior AF were analyzed from four TIMI trials. Subjects were divided into quintiles using a validated polygenic risk score (PRS) for AF. Clinical risk for AF was calculated using the CHARGE-AF model. Kaplan-Meier event rates, adjusted hazard ratios (HRs), C-indices, and net reclassification improvement were used to determine if the addition of the PRS improved prediction compared with clinical risk and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Over 2.3 years, 1018 new AF cases developed. AF PRS predicted a significant risk gradient for AF with a 40% increased risk per 1-SD increase in PRS [HR: 1.40 (1.32-1.49); P < 0.001]. Those with high AF PRS (top 20%) were more than two-fold more likely to develop AF [HR 2.45 (1.99-3.03), P < 0.001] compared with low PRS (bottom 20%). Furthermore, PRS provided an additional gradient of risk stratification on top of the CHARGE-AF clinical risk score, ranging from a 3-year incidence of 1.3% in patients with low clinical and genetic risk to 8.7% in patients with high clinical and genetic risk. The subgroup of patients with high clinical risk, high PRS, and elevated NT-proBNP had an AF risk of 16.7% over 3 years. The C-index with the CHARGE-AF clinical risk score alone was 0.65, which improved to 0.67 (P < 0.001) with the addition of NT-proBNP, and increased further to 0.70 (P < 0.001) with the addition of the PRS.
Conclusion: In patients with cardiovascular conditions, AF PRS is a strong independent predictor of incident AF that provides complementary predictive value when added to a validated clinical risk score and NT-proBNP.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10310983 | PMC |
| http://dx.doi.org/10.1093/eurheartj/ehac460 | DOI Listing |
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