A polygenic risk score for atrial fibrillation independently predicted incident AF with a 40% increased risk per 1-SD increase (HR 1.40; 95% CI 1.32-1.49; P<0.001) in cardiovascular patients.
Observational (n=36,662)
Yes
Does a polygenic risk score improve the prediction of incident atrial fibrillation in patients with cardiovascular disease compared to clinical risk scores and NT-proBNP?
A polygenic risk score for atrial fibrillation provides independent and complementary predictive value for incident AF when added to clinical risk scores and NT-proBNP in patients with cardiovascular disease.
Effect estimate: HR 1.40 (95% CI 1.32-1.49)
p-value: p=<0.001
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.
Marston et al. (Thu,) conducted a observational in Cardiovascular disease without prior atrial fibrillation (n=36,662). Polygenic risk score (PRS) for AF vs. Low PRS was evaluated on Incident atrial fibrillation (HR 1.40, 95% CI 1.32-1.49, p=<0.001). A polygenic risk score for atrial fibrillation independently predicted incident AF with a 40% increased risk per 1-SD increase (HR 1.40; 95% CI 1.32-1.49; P<0.001) in cardiovascular patients.