@article {9573, title = {A polygenic risk score of atrial fibrillation improves prediction of lifetime risk for heart failure.}, journal = {ESC Heart Fail}, year = {2024}, month = {2024 Jan 22}, abstract = {

AIMS: Heart failure (HF) has shared genetic architecture with its risk factors: atrial fibrillation (AF), body mass index (BMI), coronary heart disease (CHD), systolic blood pressure (SBP), and type 2 diabetes (T2D). We aim to assess the association and risk prediction performance of risk-factor polygenic risk scores (PRSs) for incident HF and its subtypes in bi-racial populations.

METHODS AND RESULTS: Five PRSs were constructed for AF, BMI, CHD, SBP, and T2D in White participants of the Atherosclerosis Risk in Communities (ARIC) study. The associations between PRSs and incident HF and its subtypes were assessed using Cox models, and the risk prediction performance of PRSs was assessed using C statistics. Replication was performed in the ARIC study Black and Cardiovascular Health Study (CHS) White participants. In 8624 ARIC study Whites, 1922 (31\% cumulative incidence) HF cases developed over 30~years of follow-up. PRSs of AF, BMI, and CHD were associated with incident HF (P~<~0.001), where PRS showed the strongest association [hazard ratio (HR): 1.47, 95\% confidence interval (CI): 1.41-1.53]. Only the addition of PRS to the ARIC study HF risk equation improved C statistics for 10~year risk prediction from 0.812 to 0.829 (∆C: 0.017, 95\% CI: 0.009-0.026). The PRS was associated with both incident HF with reduced ejection fraction (HR: 1.43, 95\% CI: 1.27-1.60) and incident HF with preserved ejection fraction (HR: 1.46, 95\% CI: 1.33-1.62). The associations between PRS and incident HF and its subtypes, as well as the improved risk prediction, were replicated in the ARIC study Blacks and the CHS Whites (P~<~0.050). Protein analyses revealed that N-terminal pro-brain natriuretic peptide and other 98 proteins were associated with PRS .

CONCLUSIONS: The PRS was associated with incident HF and its subtypes and had significant incremental value over an established HF risk prediction equation.

}, issn = {2055-5822}, doi = {10.1002/ehf2.14665}, author = {Alkis, Taryn and Luo, Xi and Wall, Katherine and Brody, Jennifer and Bartz, Traci and Chang, Patricia P and Norby, Faye L and Hoogeveen, Ron C and Morrison, Alanna C and Ballantyne, Christie M and Coresh, Josef and Boerwinkle, Eric and Psaty, Bruce M and Shah, Amil M and Yu, Bing} }