Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation.
Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation.
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DOI：
10.1161/circulationaha.117.031431
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发表时间：
2018-03-06
期刊：
影响因子：
37.8
通讯作者：
Lubitz SA
中科院分区：
文献类型：
--
作者：
Weng LC;Preis SR;Hulme OL;Larson MG;Choi SH;Wang B;Trinquart L;McManus DD;Staerk L;Lin H;Lunetta KL;Ellinor PT;Benjamin EJ;Lubitz SA
考虑到遗传易感性和临床风险因素负担，发生房颤（AF）的长期概率尚不清楚。我们估计了来自社区心脏研究的个体的房颤终生风险。使用约1,000个AF相关单核苷酸多态性的评分得出AF的多基因风险。使用经验证的AF事件风险评分计算每个个体的临床风险因素负担，该评分包括身高、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、心肌梗死病史和心力衰竭病史。我们估计房颤的终生风险在多基因和临床风险的三分位数内。在4，606名55岁时无AF的参与者中，580名发生AF（中位随访时间为9.4年;第25 - 75百分位数为4.4-14.3年）。55岁以后房颤的终生风险为37.1%，并且受到多基因和临床风险因素负担的显著影响。在55岁时无AF的个体中，低多基因和临床风险三分位数的患者AF的终生风险为22.3%（95%置信区间[CI]，15.4%-29.1%），而高风险三分位数的患者AF的风险为48.2%（95% CI，41.3%-55.1%）。校正遗传易感性后，较低的临床危险因素负担与较晚的房颤发作相关（P值<0.001）。在我们的社区队列中，房颤的终生风险为37%。多基因AF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AF风险的实质性梯度。
The long-term probability of developing atrial fibrillation (AF) considering genetic predisposition and clinical risk factor burden is unknown. We estimated lifetime risk of AF in individuals from the community-based Framingham Heart Study. Polygenic risk for AF was derived using a score of approximately 1,000 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, history of myocardial infarction, and history of heart failure. We estimated the lifetime risk of AF within tertiles of polygenic and clinical risk. Among 4,606 participants without AF at age 55 years, 580 developed incident AF (median follow-up, 9.4 years; 25th-75th percentile, 4.4-14.3 years). The lifetime risk of AF after age 55 years was 37.1%, and was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of AF at age 55 years, those in low polygenic and clinical risk tertiles had a lifetime risk of AF of 22.3% (95% confidence interval [CI], 15.4%-29.1%), whereas those in high risk tertiles had a risk of 48.2% (95% CI, 41.3%-55.1%). A lower clinical risk factor burden was associated with later AF onset after adjusting for genetic predisposition (P value <0.001). 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.