Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, California, United States of America.
Division of Cardiovascular Disease, Scripps Clinic-Scripps Health, La Jolla, California, United States of America.
PLoS Med. 2018 Mar 13;15(3):e1002525. doi: 10.1371/journal.pmed.1002525. eCollection 2018 Mar.
Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF.
Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF.
Prospective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings.
ClinicalTrials.gov NCT01970969.
心房颤动（AF）是最常见的心律失常，与中风风险增加有关。提高对 AF 风险最高的患者的识别能力，以便在必要时进行适当的监测和治疗，对于降低 AF 相关发病率和死亡率至关重要。多个常见的单核苷酸多态性（SNP）与 AF 的终身风险明确相关。在本研究中，我们旨在前瞻性验证以前未诊断的 AF 高危患者的 AF 遗传风险评分（GRS）。
年龄在 40 岁或以上、有 1 个 AF 临床危险因素、出现 AF 症状或首次诊断为 AF 的个体，接受基因检测和贴剂监测仪或长期 Holter 监测仪（平均佩戴时间分别为 10 天 21 小时和 13 天 18 小时）进行动态心脏节律监测。AF 事件是通过心电图、贴剂监测仪或长期 Holter 监测仪首次诊断为 AF。根据 12 个遗传风险位点的加权贡献确定每位参与者的 AF GRS。在 904 名参与者中，85 名出现 AF。他们的平均年龄为 66.2（SD 11.8）岁；38%的参与者为男性。在调整年龄、性别、吸烟状况、BMI、高血压、糖尿病、心力衰竭和先前的心肌梗死后，AF GRS 最高五分位的参与者比最低五分位的参与者更有可能（优势比 3.11；95%置信区间 1.27-7.58；p = 0.01）发生 AF 事件。研究局限性包括人群种族单一、监测节律时间有限以及与 AF 相关的 SNP 的不断发现。
前瞻性评估 AF 的 GRS 可识别出超出既定临床标准的 AF 风险升高的参与者。因此，AF 的 GRS 可以纳入总体风险评估中，以更好地识别 AF 风险最高的患者，尽管需要在更大的人群中进行进一步测试以证实这些发现。
ClinicalTrials.gov NCT01970969。
