房颤患者的遗传风险与结局相关性：EAST-AFNET4 试验中与早期节律控制的相互作用。
Association of genetic risk and outcomes in patients with atrial fibrillation: interactions with early rhythm control in the EAST-AFNET4 trial.
机构信息
Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg Eppendorf, Martinistraße 52, 20248 Hamburg, Germany.
University Center of Cardiovascular Science, University Heart and Vascular Center Hamburg, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
出版信息
Cardiovasc Res. 2023 Aug 7;119(9):1799-1810. doi: 10.1093/cvr/cvad027.
AIMS
The randomized Early Treatment of Atrial Fibrillation for Stroke Prevention Trial found that early rhythm control reduces cardiovascular events in patients with recently diagnosed atrial fibrillation (AF) compared with usual care. How genetic predisposition to AF and stroke interacts with early rhythm-control therapy is not known.
METHODS AND RESULTS
Array genotyping and imputation for common genetic variants were performed. Polygenic risk scores (PRS) were calculated for AF (PRS-AF) and ischaemic stroke risk (PRS-stroke). The effects of PRS-AF and PRS-stroke on the primary outcome (composite of cardiovascular death, stroke, and hospitalization for acute coronary syndrome or worsening heart failure), its components, and recurrent AF were determined.A total of 1567 of the 2789 trial patients were analysed [793 randomized to early rhythm control; 774 to usual care, median age 71 years (65-75), 704 (44%) women]. Baseline characteristics were similar between randomized groups. Early rhythm control reduced the primary outcome compared with usual care [HR 0.67, 95% CI: (0.53, 0.84), P < 0.001]. The randomized intervention, early rhythm control, did not interact with PRS-AF (interaction P = 0.806) or PRS-stroke (interaction P = 0.765). PRS-AF was associated with recurrent AF [HR 1.08 (01.0, 1.16), P = 0.047]. PRS-stroke showed an association with the primary outcome [HR 1.13 (1.0, 1.27), P = 0.048], driven by more heart failure events [HR 1.23 (1.05-1.43), P = 0.010] without differences in stroke [HR 1.0 (0.75, 1.34), P = 0.973] in this well-anticoagulated cohort. In a replication analysis, PRS-stroke was associated with incident AF [HR 1.16 (1.14, 1.67), P < 0.001] and with incident heart failure in the UK Biobank [HR 1.08 (1.06, 1.10), P < 0.001]. The association with heart failure was weakened when excluding AF patients [HR 1.03 (1.01, 1.05), P = 0.001].
CONCLUSIONS
Early rhythm control is effective across the spectrum of genetic AF and stroke risk. The association between genetic stroke risk and heart failure calls for research to understand the interactions between polygenic risk and treatment.
REGISTRATION
ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.
目的
早期治疗心房颤动预防中风试验发现，与常规治疗相比，早期节律控制可降低新近诊断为心房颤动（AF）患者的心血管事件。但目前尚不清楚遗传易感性与 AF 和中风之间的相互作用如何。
方法和结果
进行了常见遗传变异的阵列基因分型和推测。计算了 AF（PRS-AF）和缺血性中风风险（PRS-中风）的多基因风险评分（PRS）。确定了 PRS-AF 和 PRS-中风对主要结局（心血管死亡、中风和因急性冠脉综合征或心力衰竭恶化而住院的复合结局）、其组成部分和复发性 AF 的影响。总共分析了 2789 例试验患者中的 1567 例[793 例随机接受早期节律控制；774 例接受常规治疗，中位年龄 71 岁（65-75），704 例（44%）为女性]。随机分组之间的基线特征相似。与常规治疗相比，早期节律控制降低了主要结局[HR 0.67，95%CI：（0.53，0.84），P < 0.001]。随机干预，早期节律控制，与 PRS-AF（交互 P = 0.806）或 PRS-中风（交互 P = 0.765）无交互作用。PRS-AF 与复发性 AF 相关[HR 1.08（01.0，1.16），P = 0.047]。PRS-中风与主要结局相关[HR 1.13（1.0，1.27），P = 0.048]，这主要是由于心力衰竭事件增加[HR 1.23（1.05-1.43），P = 0.010]，而在这一抗凝良好的队列中，中风无差异[HR 1.0（0.75，1.34），P = 0.973]。在复制分析中，PRS-中风与新发 AF 相关[HR 1.16（1.14，1.67），P < 0.001]，与英国生物库的新发心力衰竭相关[HR 1.08（1.06，1.10），P < 0.001]。当排除 AF 患者时，与心力衰竭的相关性减弱[HR 1.03（1.01，1.05），P = 0.001]。
结论
早期节律控制对各种遗传 AF 和中风风险均有效。遗传中风风险与心力衰竭之间的关联需要进一步研究，以了解多基因风险和治疗之间的相互作用。
注册
ISRCTN04708680、NCT01288352、EudraCT2010-021258-20，www.easttrial.org。
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