Cardiovascular Predictive Value and Genetic Basis of Ventricular Repolarization Dynamics
Cardiovascular Predictive Value and Genetic Basis of Ventricular Repolarization Dynamics
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DOI：
10.1161/circep.119.007549
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发表时间：
2019-10-01
影响因子：
8.4
通讯作者：
Munroe, Patricia B.
中科院分区：
文献类型：
--
作者：
Ramirez, Julia;van Duijvenboden, Stefan;Munroe, Patricia B.
背景：在一般人群中早期预测心血管风险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记物，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在英国中年人群的心血管预后价值，并确定任何遗传contribution.METHODS：我们分析了ECG记录从55222个人从英国中年人口进行运动负荷试验在英国生物银行（UKB）。TMR用于测量心室复极动力学，在该队列中通过运动（运动期间的TMR，TMRex）和运动恢复（恢复期间的TMR，TMRrec）暴露。主要终点是心血管事件;次要终点是全因死亡率、室性心律失常和房颤，中位随访时间为7年。对TMRex和TMRrec进行了全基因组关联研究，并推导出遗传风险评分，并在来自完整UKB队列的独立样本中进行关联性测试（N=360631）。结果：共1743例在UKB中，3.2%接受运动负荷试验的个体发生心血管事件，TMRrec与心血管事件显著相关（风险比，1.11; P= 5x 10（-7）），独立于临床变量和其他ECG标志物。TMRrec还与全因死亡率（风险比，1.10）和室性心律失常（风险比，1.16）相关。我们共鉴定了TMRex和TMRrec的12个遗传位点，其中9个与另一个ECG标记物相关。在整个UKB队列中，TMRrec遗传风险评分前20%的个体发生心血管事件的可能性明显更高（18997，5.3%）比处于最后20%的个人（风险比，1.07; P= 6x 10（-3））。TMR和TMR遗传风险评分与英国中年人群的心血管风险显著相关，支持心室复极的时空异质性增加是心血管风险的一个基础的假设，以及TMR作为心血管风险预测因子的有效性。
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 55222 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=360631).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=5x10(-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 (18997, 5.3%) than individuals in the bottom 20% (hazard ratio, 1.07; P=6x10(-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.VISUAL OVERVIEW: A visual overview is available for this article.