Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD; BSICoS Group, Aragón Institute for Engineering Research (I3A), IIS Aragón, University of Zaragoza, Zaragoza, Aragón, Spain.
Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD; Department of Clinical Physiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Am Heart J. 2014 Nov;168(5):749-56. doi: 10.1016/j.ahj.2014.07.010. Epub 2014 Jul 24.
Corrected QT interval (QTc) is shorter in postpubertal men than in women; however, QTc lengthens as men age and testosterone levels decrease. Animal studies have demonstrated that testosterone decreases L-type calcium current and increases slow delayed rectifier potassium current; however, it is not known how these contribute to QTc differences by sex and age in humans. We separately analyzed early versus late repolarization duration and performed simulations of the effect of testosterone on the electrocardiogram (ECG) to examine the mechanism of sex and age differences in QTc in humans.
Twelve-lead ECGs from 2,235 healthy subjects (41% women) in Thorough QT studies were analyzed to characterize sex- and age-dependent differences in depolarization (QRS), early repolarization (J-T(peak)), and late repolarization (T(peak)-T(end)). In addition, we simulated the effects of testosterone on calcium current, slow delayed rectifier potassium current, and surface ECG intervals.
QTc was shorter in men than in women (394 ± 16 vs 408 ± 15 milliseconds, P < .001), which was due to shorter early repolarization (213 ± 16 vs 242 ± 16 milliseconds, P < .001), as men had longer depolarization (94 ± 7 vs 89 ± 7 milliseconds, P < .001) and longer late repolarization (87 ± 10 vs 78 ± 9 milliseconds, P < .001). Sex difference in QTc decreased with age and was due to changes in early repolarization. Simulations showed that the early repolarization changes were most influenced by testosterone's effect on calcium current.
Shorter QTc in men compared to women is explained by shorter early repolarization, and this difference decreases with age. These sex and age differences in repolarization appear to be caused by testosterone effects on calcium current.
在青春期后，男性的校正 QT 间期（QTc）比女性短；然而，随着男性年龄的增长和睾丸激素水平的下降，QTc 会延长。动物研究表明，睾丸激素会降低 L 型钙电流并增加缓慢延迟整流钾电流；然而，目前尚不清楚这些机制如何导致人类中性别和年龄对 QTc 的影响。我们分别分析了早期和晚期复极持续时间，并对睾丸激素对心电图（ECG）的影响进行了模拟，以研究人类 QTc 中性别和年龄差异的机制。
对来自 Thorough QT 研究的 2235 名健康受试者（41%为女性）的 12 导联心电图进行分析，以描述去极化（QRS）、早期复极（J-Tpeak）和晚期复极（Tpeak-Tend）的性别和年龄依赖性差异。此外，我们模拟了睾丸激素对钙电流、缓慢延迟整流钾电流和体表心电图间期的影响。
男性的 QTc 比女性短（394±16 与 408±15 毫秒，P<.001），这是由于早期复极更短（213±16 与 242±16 毫秒，P<.001），因为男性的去极化（94±7 与 89±7 毫秒，P<.001）和晚期复极（87±10 与 78±9 毫秒，P<.001）更长。QTc 的性别差异随年龄而减小，这归因于早期复极的变化。模拟结果表明，早期复极的变化受睾丸激素对钙电流的影响最大。
与女性相比，男性的 QTc 较短，这是由于早期复极较短，并且这种差异随年龄的增长而减小。这些复极的性别和年龄差异似乎是由睾丸激素对钙电流的影响引起的。
