Prediction of atrial and ventricular arrhythmias using multiple cardiovascular risk-factor polygenic risk scores

Abstract

Background: Atrial fibrillation (AF) prediction improves by combining clinical scores with a polygenic risk score (PRS) for AF (AF-PRS), but there are limited studies of PRS for ventricular arrhythmia (VA) prediction.

Objective: We assessed the value of including multiple PRS for cardiovascular risk factors (CV-PRS) for incident AF and VA prediction.

Methods: We used 158,733 individuals of European ancestry from UK Biobank to build 3 models for AF: CHARGE-AF (AF1), AF1 + AF-PRS (AF2), AF2 + CV-PRS (AF3). Models for VA included sex and age (VA1), VA1 + coronary artery disease (CAD) PRS (CAD-PRS, VA2), and VA2 + CV-PRS (VA3), conducting separate analyses in subjects with and without ischemic heart disease (IHD). Performance was evaluated in individuals of European (N = 158,733), African (N = 7200), South Asian (N = 9241) and East Asian (N = 2076) ancestry from UK Biobank.

Results: AF2 had a higher C-index than AF1 (0.762 vs 0.746, P < .001), marginally improving to 0.765 for AF3 (P < .001, including PRS for heart failure, electrocardiogram and cardiac magnetic resonance measures). In South Asians, AF2 C-index was higher than AF1 (P < .001). For VA, the C-index for VA2 was greater than VA1 (0.692 vs 0.681, P < .001) in Europeans, which was also observed in South Asians (P < .001). VA3 improved prediction of VA in individuals with IHD.

Conclusion: CV-PRS improved AF prediction compared to CHARGE-AF and AF-PRS. A CAD-PRS improved VA prediction, while CV-PRS contributed in IHD. AF- and CAD-PRS were transferable to individuals of South Asian ancestry. Our results inform of the use of CV-PRS for personalized screening.

Keywords: Atrial fibrillation; Polygenic risk scores; Risk prediction; UK Biobank; Ventricular arrhythmia.