Abstract 9110: Use of a Genetic Risk Score to Predict Atrial Fibrillation in Patients With Cardiovascular Disease

Background: Early detection of atrial fibrillation (AF) could permit earlier anticoagulation and thus potentially reduce risk of embolic stroke. A validated genetic risk score (GRS) has been shown to predict AF risk but its clinical utility beyond established AF risk factors is unclear. Methods: We performed a prospective cohort analysis in pts w/o prior AF from 4 TIMI trials [SOLID-TIMI 52, SAVOR-TIMI 53, PEGASUS-TIMI 54, FOURIER (TIMI 59)]. Pts were divided into genetic risk quintiles using a validated 1,018 SNP GRS for AF. Clinical risk for AF was also calculated using the validated CHARGE-AF model (age, ht, wt, SBP, DBP, anti-HTN med, DM, CHF, MI, smoking). 3-year KM rates and adjusted HRs were calculated across clinical and genetic risk groups. C-index was used to determine if the addition of GRS improved AF prediction compared with clinical risk and NT-proBNP. Results: In 36,663 pts followed for a median of 2.3 yrs, 1,018 new AF cases (2.8%) were identified. AF GRS predicted a significant risk gradient for AF with a 33% increased risk per 1-SD increase in GRS (HR 1.33 [95%CI 1.26-1.41]; p<0.001). Those in the top quintile of AF GRS were more than 2-fold more likely to develop AF (HR 2.26 [1.84-2.78], p<0.001) compared with the bottom quintile. This risk prediction was on par with age and stronger than any other clinical risk factor. Further, GRS provided an additional gradient of risk stratification on top of the CHARGE-AF clinical risk score, such that pts with high GRS and CHARGE-AF score had an 8.1% 3-year AF risk (Fig) . The C-index for CHARGE-AF was 0.64 (0.63-0.66); addition of NT-proBNP raised the C-index to 0.67 (0.65-0.69), and inclusion of GRS increased it further to 0.69 (0.67-0.71) (p<0.001). Conclusion: In pts with CV disease, AF GRS is a strong independent predictor of incident AF that provides complementary predictive value when added to a validated clinical risk score. AF GRS may be a clinically useful tool to identify very high-risk pts for consideration of AF screening.