Cardiology Division, University of Rochester Medical Center, Rochester, NY 14642, USA.
Heart Rhythm. 2012 Jun;9(6):892-8. doi: 10.1016/j.hrthm.2012.01.020. Epub 2012 Jan 28.
Men and women with type 1 long QT syndrome (LQT1) exhibit time-dependent differences in the risk for cardiac events.
We hypothesized that sex-specific risk for LQT1 is related to the location and function of the disease-causing mutation in the KCNQ1 gene.
The risk for life-threatening cardiac events (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years was assessed among 1051 individuals with LQT1 (450 men and 601 women) by the location and function of the LQT1-causing mutation (prespecified as mutations in the intracellular domains linking the membrane-spanning segments [ie, S2-S3 and S4-S5 cytoplasmic loops] involved in adrenergic channel regulation vs other mutations).
Multivariate analysis showed that during childhood (age group: 0-13 years) men had >2-fold (P < .003) increased risk for ACA/SCD than did women, whereas after the onset of adolescence the risk for ACA/SCD was similar between men and women (hazard ratio = 0.89 [P = .64]). The presence of cytoplasmic-loop mutations was associated with a 2.7-fold (P < .001) increased risk for ACA/SCD among women, but it did not affect the risk among men (hazard ratio 1.37; P = .26). Time-dependent syncope was associated with a more pronounced risk-increase among men than among women (hazard ratio 4.73 [P < .001] and 2.43 [P = .02], respectively), whereas a prolonged corrected QT interval (≥ 500 ms) was associated with a higher risk among women than among men.
Our findings suggest that the combined assessment of clinical and mutation location/functional data can be used to identify sex-specific risk factors for life-threatening events for patients with LQT1.
患有 1 型长 QT 综合征（LQT1）的男性和女性在发生心脏事件的风险方面存在时间依赖性差异。
我们假设导致 LQT1 的致病突变的位置和功能与 LQT1 患者的性别特异性风险相关。
通过 LQT1 致病突变的位置和功能（预设为涉及肾上腺素能通道调节的跨膜段之间的细胞内域的突变[即 S2-S3 和 S4-S5 细胞质环]与其他突变），评估了 1051 名 LQT1 患者（450 名男性和 601 名女性）从出生到 40 岁时危及生命的心脏事件（包括心搏骤停前[ACA]或心源性猝死[SCD]）的风险。
多变量分析显示，在儿童期（年龄组：0-13 岁），男性发生 ACA/SCD 的风险比女性高 2 倍以上（P<0.003），而在青春期后，男女发生 ACA/SCD 的风险相似（危险比=0.89 [P=0.64]）。细胞质环突变与女性发生 ACA/SCD 的风险增加 2.7 倍相关（P<0.001），但对男性没有影响（危险比 1.37；P=0.26）。时间依赖性晕厥与男性比女性的风险增加更明显相关（危险比分别为 4.73 [P<0.001]和 2.43 [P=0.02]），而校正后的 QT 间期延长（≥500 ms）与女性的风险升高相关高于男性。
我们的研究结果表明，综合评估临床和突变位置/功能数据可用于确定 LQT1 患者发生危及生命事件的性别特异性危险因素。
