Atrial Fibrillation Screening According to Genetic Risk: A Secondary Analysis of the Randomized LOOP Study.

This study investigated the efficacy of AF screening for stroke prevention based on a PRS for AF.

本研究调查了基于心房颤动（AF）的PRS进行心房颤动筛查在预防中风方面的有效性。

Methods

This prespecified post hoc analysis of the randomized LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals) study included 5,656 AF-naive individuals aged ≥70 years with stroke risk factors and available genetic data.

这项预先指定的事后分析包括了5656名年龄≥70岁、有中风风险因素且有可用遗传数据的房颤初发患者，他们来自随机化的LOOP（使用植入式环形记录仪连续心电监测以预防高风险个体中风）研究。

The participants were randomized 1:3 for screening with an implantable loop recorder (ILR) vs usual care.

参与者被随机分为1:3，一组接受植入式环形记录仪（ILR）筛查，另一组接受常规护理。

Genetic risk of AF was assessed using a PRS for AF (PRSAF).

使用房颤遗传风险评分（PRSAF）评估房颤的遗传风险。

The primary outcome was a composite of stroke and systemic embolism (SE).

主要结果是中风和全身性栓塞（SE）的复合结果。

Interaction between the randomization arm and PRSAF was assessed in cause-specific Cox regressions for the full cohort and across the observed range of polygenic risk using a continuous prediction grid.

在全队列中，使用连续预测网格评估了随机化组与多基因风险评分（PRSAF）之间的相互作用，并在观察到的多基因风险范围内进行了特定原因的Cox回归分析。

Secondary analyses included models stratified by PRS level, gene-screening interactions for major bleeding events, and associations between PRSAF and AF burden (≥1 episode lasting ≥24 hours among participants with ILR-detected AF).

次要分析包括按多基因风险评分（PRS）水平分层的模型、主要出血事件的基因筛查相互作用，以及多基因风险评分（PRSAF）与房颤（AF）负担（在有植入式环路记录器（ILR）检测到AF的参与者中，≥1次持续≥24小时的发作）之间的关联。

Results

Over a median follow-up period of 5.4 years, 969 participants (17.1%) received a diagnosis of AF, 296 (5.2%) had stroke/SE, and 206 (3.6%) had major bleeding.

在中位随访期为5.4年的时间里，969名参与者（17.1%）被诊断为房颤（AF），296名（5.2%）经历了中风/全身性栓塞（SE），206名（3.6%）发生了主要出血事件。

PRSAF was associated with higher rates of AF (HR per SD increase: 1.20; 95% CI: 1.13-1.28; P < 0.001).

PRSAF与房颤（AF）的较高发生率相关（每标准差增加的危险比：1.20；95%置信区间：1.13-1.28；P < 0.001）。

A significant interaction was observed between ILR screening and PRSAF for stroke/SE (Pinteraction = 0.006).

观察到植入式循环记录器筛查与房颤相关卒中评分中位数及以上之间对于中风/SE存在显著的相互作用（Pinteraction = 0.006）。

ILR screening was associated with lower rates of stroke/SE in individuals with PRSAF ≥median (HR: 0.65; 95% CI: 0.43-0.97; P = 0.036) but not in those with PRSAF <median (HR: 1.06; 95% CI: 0.72-1.57; P = 0.75).

在房颤相关卒中评分中位数及以上的个体中，植入式循环记录器筛查与较低的中风/SE发生率相关（HR: 0.65; 95% CI: 0.43-0.97; P = 0.036），但在房颤相关卒中评分中位数以下的个体中则没有这种相关性（HR: 1.06; 95% CI: 0.72-1.57; P = 0.75）。

ILR screening was associated with higher rates of major bleeding at lower levels of PRSAF (Pinteraction = 0.036), corresponding to a HR of 1.71 (95% CI: 1.12-2.64; P = 0.011) in those with PRSAF <median.

ILR筛查与较低PRSAF水平下的主要出血率较高相关（Pinteraction = 0.036），在PRSAF <中位数的个体中，相应的风险比为1.71（95%置信区间：1.12-2.64；P = 0.011）

A 1-SD increase in PRSAF was associated with an OR of 1.35 (95% CI: 1.02-1.78; P = 0.037) for having ≥1 AF episode lasting ≥24 hours.

PRSAF每增加1个标准差，发生≥1次持续≥24小时的AF发作的几率比为1.35（95%置信区间：1.02-1.78；P = 0.037）

Conclusions

ILR screening for AF was associated with a significant reduction in stroke/SE in individuals with higher genetic risk of AF but not in those with lower genetic risk.

对于具有较高房颤遗传风险的个体，植入式环路记录器(ILR)筛查与中风/全身性栓塞(SE)发生率显著降低相关，但对于遗传风险较低的个体则无此相关性。

These hypothesis-generating findings indicate that genetic predisposition may aid in selecting individuals who benefit from AF screening.

这些生成假设的发现表明，遗传倾向可能有助于选择从房颤筛查中受益的个体。