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. 2025 Mar 18;14(6):e038074.
doi: 10.1161/JAHA.124.038074. Epub 2025 Mar 13.

Clinical and Genetic Risk Factors Predict Atrial Fibrillation on the Basis of Hypertrophic Cardiomyopathy

Young Shin Lee  1 , Pil-Sung Yang  2 , Eunsun Jang  3 , Daehoon Kim  3 , Hee Tae Yu  3 , Tae-Hoon Kim  3 , Jae-Sun Uhm  3 , Jung-Hoon Sung  2 , Hui-Nam Pak  3 , Moon-Hyoung Lee  3 , Jin-Bae Kim  1 , Boyoung Joung  3
Affiliations

Clinical and Genetic Risk Factors Predict Atrial Fibrillation on the Basis of Hypertrophic Cardiomyopathy

Young Shin Lee et al. J Am Heart Assoc. .

Abstract

Background: Clinical and genetic predispositions are significant in predicting atrial fibrillation (AF); however, their role in patients with hypertrophic cardiomyopathy (HCM) remains unclear. This study aims to elucidate the impact of clinical and genetic risk factors on the development of AF in patients with and without HCM.

Methods and results: This retrospective analysis involved data from the UK Biobank cohort. Participants were divided into 3 groups based on their validated polygenic risk score for AF: the bottom 10% as low risk, the top 10% as high risk, and the rest as intermediate risk. We assessed the incidence of AF and cardiovascular complications and analyzed its predictors, including genetic risk. We examined 1180 patients with HCM (mean age, 61.1±7.1; 63.0% men) and 476 238 participants without HCM (mean age, 57.0±8.1; 45.3% men). During the 11.6-year follow-up period, the age- and sex-adjusted AF incidence rates for the low, intermediate, and high genetic risk groups were 2.4, 3.6, and 5.4 per 100 person-years in participants with HCM and 0.2, 0.5, and 1.0 per 100 person-years in participants without HCM, respectively. Genetic risk, evaluated as a continuous variable using polygenic risk score, was a less significant predictor of AF in the HCM group (hazard ratio [HR], 1.35 [95% CI, 1.21-1.49]) than in non-HCM group (HR, 1.57 [95% CI, 1.56-1.59]; P=0.005 for interaction). A high genetic risk was significantly associated with the risk of cardiovascular complications in both groups.

Conclusions: Genetic predisposition is associated with the development of AF and cardiovascular complications in people with and without HCM; this association was weaker in the HCM group.

Keywords: UK Biobank; atrial fibrillation; hypertrophic cardiomyopathy; polygenic risk score.

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Conflict of interest statement

Dr Joung has served as a speaker for Bayer, BMS/Pfizer, Medtronic, and Daiichi‐Sankyo and received research funds from Medtronic and Abbott. No fees were received personally. The remaining authors have no conflicts to declare.

Figures

Figure 1
Figure 1. Flow diagram of the study population.
AF indicates atrial fibrillation; HCM, hypertrophic cardiomyopathy; and PRS, polygenic risk score.
Figure 2
Figure 2. Cumulative incidence of AF according to genetic risk in total cohort.
AF indicates atrial fibrillation; HCM, hypertrophic cardiomyopathy; and PRS, polygenic risk score.
Figure 3
Figure 3. Longitudinal association between genetic risk and incident AF.
Hazard ratios are adjusted for age, sex, and cardiovascular disease risk factors. AF indicates atrial fibrillation; BMI, body mass index; HCM, hypertrophic cardiomyopathy; HR, hazard ratio; MI, myocardial infarction; and PRS, polygenic risk score.
Figure 4
Figure 4. Spline curve of adjusted HR for AF risk according to PRS.
HRs are adjusted for age, sex, and cardiovascular disease risk factors. AF indicates atrial fibrillation; HCM, hypertrophic cardiomyopathy; HR, hazard ratio; and PRS, polygenic risk score.
See this image and copyright information in PMC

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