Polygenic Risk and Cardiovascular Event Risk in Patients With Atrial Fibrillation With Low to Intermediate Stroke Risk

Abstract

Background: The clinical utility of the polygenic risk score in predicting cardiovascular events in patients with atrial fibrillation (AF) has not yet been established. This study aimed to determine whether the polygenic risk score for AF might be useful in the risk stratification of AF-related cardiovascular events.

Methods and results: This study included 9597 oral anticoagulation-naive patients with AF with a CHA₂DS₂-VA (congestive heart failure; hypertension; age ≥75 years; diabetes; prior stroke or transient ischemic attack or thromboembolism; vascular disease; and age 65-74 years) score of 0 or 1 from the UK Biobank. Patients were stratified according to polygenic risk score tertiles and observed for the occurrence of ischemic stroke or systemic embolism, myocardial infarction, and heart failure hospitalization. The risks of incident events associated with the polygenic risk score were investigated using inverse probability of treatment weighting. Of 9597 individuals, 3800 (39.6%) were women and the mean±SD age was 65.3±6.4 years. During a median follow-up of 4.6 years (interquartile range, 1.7-7.9 years), the incidence rates of ischemic stroke or systemic embolism, myocardial infarction, and heart failure hospitalization were 0.83, 0.42, and 0.61 per 100 person-years, respectively. Compared with low genetic risk, high genetic risk was associated with a hazard ratio of 1.38 (95% CI, 1.08-1.76; P=0.011) for ischemic stroke or systemic embolism, 1.15 (95% CI, 0.82-1.61; P=0.422) for myocardial infarction, and 1.02 (95% CI, 0.78-1.34; P=0.895) for heart failure hospitalization.

Conclusions: In patients with AF with low-intermediate stroke risk, genetic risk for AF is associated with increased risk of stroke or systemic embolism.

Keywords: atrial fibrillation; polygenic risk score; stroke risk.

Figure 1. Study population.

CHA₂DS₂‐VA indicates congestive heart failure; hypertension; age ≥75 years; diabetes; prior stroke or transient ischemic attack or thromboembolism; vascular disease; and age 65 to 74 years.

Figure 2. Weighted incidence rate of ischemic stroke or systemic embolism, myocardial infarction, and HF hospitalization, stratified by clinical risk factors and AF PRS.

AF indicates atrial fibrillation; CHA₂DS₂‐VA, congestive heart failure; hypertension; age ≥75 years; diabetes; stroke, transient ischemic attack, thromboembolism; vascular disease; and age 65 to 74 years; HF, heart failure; and PRS, polygenic risk score.

Figure 3. Weighted cumulative incidence of ischemic stroke or systemic embolism, myocardial infarction, and HF hospitalization, stratified by AF PRS. AF indicates atrial fibrillation; HF, heart failure; and PRS, polygenic risk score.

Figure 4. Nonlinear dose–response analysis of atrial fibrillation polygenic risk score and the risk of ischemic stroke or systemic embolism, myocardial infarction, and HF hospitalization. HF indicates heart failure.