Background: The long-term probability of developing atrial fibrillation (AF) considering genetic predisposition and clinical risk factor burden is unknown.

Methods: We estimated the lifetime risk of AF in individuals from the community-based Framingham Heart Study. Polygenic risk for AF was derived using a score of ≈1000 AF-associated single-nucleotide polymorphisms. Clinical risk factor burden was calculated for each individual using a validated risk score for incident AF comprised of height, weight, systolic and diastolic blood pressure, current smoking status, antihypertensive medication use, diabetes mellitus, history of myocardial infarction, and history of heart failure. We estimated the lifetime risk of AF within tertiles of polygenic and clinical risk.

Results: Among 4606 participants without AF at 55 years of age, 580 developed incident AF (median follow-up, 9.4 years; 25th–75th percentile, 4.4–14.3 years). The lifetime risk of AF >55 years of age was 37.1% and was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of AF at 55 years of age, those in low-polygenic and clinical risk tertiles had a lifetime risk of AF of 22.3% (95% confidence interval, 15.4−9.1), whereas those in high-risk tertiles had a risk of 48.2% (95% confidence interval, 41.3−55.1). A lower clinical risk factor burden was associated with later AF onset after adjusting for genetic predisposition (P<0.001).

Conclusions: In our community-based cohort, the lifetime risk of AF was 37%. Estimation of polygenic AF risk is feasible and together with clinical risk factor burden explains a substantial gradient in long-term AF risk.

中文翻译：

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心房颤动的遗传倾向、临床危险因素负担和终生风险

背景：考虑到遗传倾向和临床危险因素负担，发生心房颤动（AF）的长期概率尚不清楚。

方法：我们根据基于社区的弗雷明汉心脏研究估计了个体的终生房颤风险。 AF 的多基因风险是通过 AF 相关单核苷酸多态性评分约 1000 得出的。使用经验证的房颤事件风险评分计算每个人的临床风险因素负担，包括身高、体重、收缩压和舒张压、当前吸烟状况、抗高血压药物使用、糖尿病、心肌梗塞病史和心力衰竭病史。我们在多基因风险和临床风险的三分位数内估计了 AF 的终生风险。

结果：在 4606 名 55 岁无房颤的参与者中，有 580 人发生了房颤（中位随访时间，9.4 年；第 25-75 个百分位数，4.4-14.3 年）。 >55 岁 AF 的终生风险为 37.1%，并且很大程度上受到多基因和临床危险因素负担的影响。在 55 岁时没有发生 AF 的个体中，那些处于低多基因和临床风险三分位的人，终生发生 AF 的风险为 22.3%（95% 置信区间，15.4−9.1），而那些处于高风险三分位的人，终生发生 AF 的风险为48.2%（95%置信区间，41.3−55.1）。调整遗传易感性后，较低的临床危险因素负担与较晚的 AF 发病相关（ P <0.001）。

结论：在我们基于社区的队列中，房颤的终生风险为 37%。多基因房颤风险的估计是可行的，并且与临床风险因素负担一起解释了长期房颤风险的显着梯度。