Age and genetics as risk factors for the development of atrial fibrillation

1. In this prospective cohort study, age was found to be the most prominent risk factor for the development of atrial fibrillation (AF) in adults between 40 to 69 years old in the United Kingdom.

2. Both risk factor burden and genetic predisposition were found to play a pivotal role in the risk of developing AF, especially among male participants and those of a younger age.

Evidence Rating Level: 2 (Good)

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, posing a significant worldwide health and economic burden. Current risk prediction tools may not be up to date with current rates and risk factors for AF. The estimate of the 10-year risk of AF should integrate modifiable risk factors as well as genetic predisposition; this study aims to estimate the 10-year risk of AF in various subgroups with different genetic and clinical factors and to evaluate the combined effects and potential interactions of risk factors and genetic predisposition on the incidence of AF. Participants aged 40 – 69 years old enrolled from 2006 to 2010 in the UK Biobank were included in the analysis. They were divided into three categories: index ages 45, 55, and 65 years according to the ages at assessment. Participants free of AF were followed up from the late dates of their index age until the first AF occurrence, death, loss to follow-up, end of ten-year follow-up, or March 31, 2021. The primary outcome studied was the incidence of AF, including both atrial fibrillation and flutter. In total, 348904 participants were included in the statistical analysis, defined by index ages of 45 (n = 84,206), 55 (n = 117,520), and 65 (n = 147,178) years. The overall 10-year risks of AF were 0.67% (95% CI, 0.61% – 0.73%) for index age 45 years, 2.05% (95% CI, 1.96 – 2.13%) for index age 55 years, and 6.34% (95% CI, 6.21% – 6.46%) for index age 65 years. History of myocardial infarction or heart failure had the strongest association with a 10-year risk of AF at each index age, followed by diabetes mellitus and alcohol consumption. Generally, participants with a higher risk factor burden or higher polygenic risk score (based on their genetic predisposition to AF) had a higher risk of developing AF. Overall, this large prospective study identified the overall 10-year risks of AF in the study population, as well as the variation depending on risk factor burden and genetic predisposition. The 10-year risk was highest in men with high PRS and elevated risk factor burden at each index age. There are three clinical implications; first: risk factor burden and genetic predisposition are pivotal in the risk of AF; second: age was the most prominent risk factor for AF; and third: at younger ages, earlier onset of AF may result from interactions of elevated risk burdens and PRS. A major limitation of this study was that not all potential risk factors for AF were included in this study, and an under-measured risk factor burden may potentially affect the results. However, this large prospective study is an important step to better characterize the risk of developing AF, including genetic factors, especially with current AF incidence rates.

Click to read the study in BMC Medicine

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