Cardiovascular Predictive Value and Genetic Basis of Ventricular Repolarization Dynamics.

J. Ramírez, S. van Duijvenboden, N. Aung, P. Laguna, E. Pueyo, A. Tinker, P. Lambiase, M. Orini, P. Munroe
{"title":"Cardiovascular Predictive Value and Genetic Basis of Ventricular Repolarization Dynamics.","authors":"J. Ramírez, S. van Duijvenboden, N. Aung, P. Laguna, E. Pueyo, A. Tinker, P. Lambiase, M. Orini, P. Munroe","doi":"10.1161/CIRCEP.119.007549","DOIUrl":null,"url":null,"abstract":"BACKGROUND\nEarly prediction of cardiovascular risk in the general population remains an important issue. The T-wave morphology restitution (TMR), an ECG marker quantifying ventricular repolarization dynamics, is strongly associated with cardiovascular mortality in patients with heart failure. Our aim was to evaluate the cardiovascular prognostic value of TMR in a UK middle-aged population and identify any genetic contribution.\n\n\nMETHODS\nWe analyzed ECG recordings from 55 222 individuals from a UK middle-aged population undergoing an exercise stress test in UK Biobank (UKB). TMR was used to measure ventricular repolarization dynamics, exposed in this cohort by exercise (TMR during exercise, TMRex) and recovery from exercise (TMR during recovery, TMRrec). The primary end point was cardiovascular events; secondary end points were all-cause mortality, ventricular arrhythmias, and atrial fibrillation with median follow-up of 7 years. Genome-wide association studies for TMRex and TMRrec were performed, and genetic risk scores were derived and tested for association in independent samples from the full UKB cohort (N=360 631).\n\n\nRESULTS\nA total of 1743 (3.2%) individuals in UKB who underwent the exercise stress test had a cardiovascular event, and TMRrec was significantly associated with cardiovascular events (hazard ratio, 1.11; P=5×10-7), independent of clinical variables and other ECG markers. TMRrec was also associated with all-cause mortality (hazard ratio, 1.10) and ventricular arrhythmias (hazard ratio, 1.16). We identified 12 genetic loci in total for TMRex and TMRrec, of which 9 are associated with another ECG marker. Individuals in the top 20% of the TMRrec genetic risk score were significantly more likely to have a cardiovascular event in the full UKB cohort (18 997, 5.3%) than individuals in the bottom 20% (hazard ratio, 1.07; P=6×10-3).\n\n\nCONCLUSIONS\nTMR and TMR genetic risk scores are significantly associated with cardiovascular risk in a UK middle-aged population, supporting the hypothesis that increased spatio-temporal heterogeneity of ventricular repolarization is a substrate for cardiovascular risk and the validity of TMR as a cardiovascular risk predictor.","PeriodicalId":10167,"journal":{"name":"Circulation: Arrhythmia and Electrophysiology","volume":"46 1","pages":"e007549"},"PeriodicalIF":0.0000,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"15","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation: Arrhythmia and Electrophysiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1161/CIRCEP.119.007549","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 15

Abstract

BACKGROUND Early prediction of cardiovascular risk in the general population remains an important issue. The T-wave morphology restitution (TMR), an ECG marker quantifying ventricular repolarization dynamics, is strongly associated with cardiovascular mortality in patients with heart failure. Our aim was to evaluate the cardiovascular prognostic value of TMR in a UK middle-aged population and identify any genetic contribution. METHODS We analyzed ECG recordings from 55 222 individuals from a UK middle-aged population undergoing an exercise stress test in UK Biobank (UKB). TMR was used to measure ventricular repolarization dynamics, exposed in this cohort by exercise (TMR during exercise, TMRex) and recovery from exercise (TMR during recovery, TMRrec). The primary end point was cardiovascular events; secondary end points were all-cause mortality, ventricular arrhythmias, and atrial fibrillation with median follow-up of 7 years. Genome-wide association studies for TMRex and TMRrec were performed, and genetic risk scores were derived and tested for association in independent samples from the full UKB cohort (N=360 631). RESULTS A total of 1743 (3.2%) individuals in UKB who underwent the exercise stress test had a cardiovascular event, and TMRrec was significantly associated with cardiovascular events (hazard ratio, 1.11; P=5×10-7), independent of clinical variables and other ECG markers. TMRrec was also associated with all-cause mortality (hazard ratio, 1.10) and ventricular arrhythmias (hazard ratio, 1.16). We identified 12 genetic loci in total for TMRex and TMRrec, of which 9 are associated with another ECG marker. Individuals in the top 20% of the TMRrec genetic risk score were significantly more likely to have a cardiovascular event in the full UKB cohort (18 997, 5.3%) than individuals in the bottom 20% (hazard ratio, 1.07; P=6×10-3). CONCLUSIONS TMR and TMR genetic risk scores are significantly associated with cardiovascular risk in a UK middle-aged population, supporting the hypothesis that increased spatio-temporal heterogeneity of ventricular repolarization is a substrate for cardiovascular risk and the validity of TMR as a cardiovascular risk predictor.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
心室复极动力学的心血管预测价值及遗传基础。
背景:普通人群心血管风险的准确预测仍然是一个重要的问题。t波形态恢复(TMR)是一种量化心室复极动力学的心电图标志物,与心力衰竭患者的心血管死亡率密切相关。我们的目的是评估TMR在英国中年人群中的心血管预后价值,并确定任何遗传贡献。方法:我们分析了来自英国中年人群的55222个人的心电图记录,这些人在英国生物银行(UKB)进行了运动应激测试。TMR用于测量该队列中通过运动(运动期间的TMR, TMRex)和运动后恢复(恢复期间的TMR, TMRrec)暴露的心室复极动力学。主要终点为心血管事件;次要终点为全因死亡率、室性心律失常和心房颤动,中位随访时间为7年。对TMRex和TMRrec进行全基因组关联研究,并在UKB全队列(N= 360631)的独立样本中得出遗传风险评分并进行关联测试。结果接受运动应激试验的UKB患者中,共有1743人(3.2%)发生心血管事件,TMRrec与心血管事件显著相关(风险比1.11;P=5×10-7),与临床变量和其他心电图指标无关。TMRrec还与全因死亡率(风险比为1.10)和室性心律失常(风险比为1.16)相关。我们共鉴定出TMRex和TMRrec的12个遗传位点,其中9个与另一个ECG标志物相关。TMRrec遗传风险评分前20%的个体在整个UKB队列中发生心血管事件的可能性(18 997,5.3%)显著高于后20%的个体(风险比,1.07;P = 6×三分)。结论:在英国中年人群中,stmr和TMR遗传风险评分与心血管风险显著相关,支持了心室复极时空异质性增加是心血管风险的基础的假设,以及TMR作为心血管风险预测因子的有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Coronary Sinus Metabolite 12,13-diHOME Is a Novel Biomarker for Left Atrial Remodeling in Patients With Atrial Fibrillation Impact of Contact Force on Pulsed Field Ablation Outcomes Using Focal Point Catheter Characteristics of Right-Sided Accessory Pathways Associated With Right Cardiac Veins Prognostic Impact of Sinus Rhythm in Atrial Fibrillation Patients: Separating Rhythm Outcomes From Randomized Strategy Findings From the CABANA Trial Trends Favoring an Anatomical Approach to Radiofrequency Catheter Ablation of Idiopathic Ventricular Arrhythmias Originating From the Left Ventricular Summit
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1