Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study

Abstract

BackgroundAtrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF.Methods and findingsIndividuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27–7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF.ConclusionsProspective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings.Trial registrationClinicalTrials.gov NCT01970969

Effect of a Home-Based Wearable Continuous ECG Monitoring Patch on Detection of Undiagnosed Atrial Fibrillation

“…The addition of genetic risk factors will allow for even greater refinement. 1,23 It is possible that individuals with asymptomatic AF diagnosed only by ECG represent a different population than those whose AF manifests clinically. Therefore, to optimize future screening programs, the significance of short episodes of AF, especially when asymptomatic, will require greater clarity.…”

Clinical Overview of Obesity and Diabetes Mellitus as Risk Factors for Atrial Fibrillation and Sudden Cardiac Death

“…Predisposition to AF appears to also be influenced by polygenic risk factors, though their clinical utility is not clear at this time (Muse et al, 2018; Nielsen et al, 2018; Weng et al, 2018). Trends from long-term longitudinal cohort studies in the United States have also found increasing prevalence of AF though AF incidence has been stable (Schnabel et al, 2015).…”

Genetic risk scores to predict the prognosis of chronic heart failure patients in Chinese Han

“…GRS was used to identify patients with Mendelian and complex disease 25 patterns known as loci for HF risk factors, such as CAD, Cardiometabolic Disease, 8,26 Blood Pressure 9 and atrial fibrillation. 27 Heart failure has similar or worse prognosis when compared to most cancers. 28 Traditional risk factors 20 have been used in risk prediction.…”