title: Risk of recurrent cardiac events after onset of menopause in women with congenital long-QT syndrome types 1 and 2.
abstract: BACKGROUND
  Women with congenital long-QT syndrome experience an increased risk for cardiac events after the onset of adolescence that is more pronounced among carriers of the LQT2 genotype. We hypothesized that the hormonal changes associated with menopause may affect clinical risk in this population.
  
  
  RESULTS
  We used a repeated-events analysis to evaluate the risk for recurrent syncope during the menopause transition and postmenopausal periods (5 years before and after the age at onset of menopause, respectively) among 282 LQT1 (n=151) and LQT2 (n=131) women enrolled in the Long-QT Syndrome Registry. Multivariate analysis showed that the risk for recurrent syncope (n=150) among LQT2 women was significantly increased during both menopause transition (hazard ratio, 3.38; P=0.005) and the postmenopausal period (hazard ratio, 8.10; P<0.001) compared with the reproductive period. The risk increase was evident among women who did or did not receive estrogen therapy. In contrast, among LQT1 women, the onset of menopause was associated with a reduction in the risk for recurrent syncope (hazard ratio, 0.19; P=0.05; P=0.02 for genotype-by-menopause interaction). Only 22 women (8%) experienced aborted cardiac arrest or sudden cardiac death during follow-up. The frequency of aborted cardiac arrest/sudden cardiac death showed a similar genotype-specific association with the onset of menopause.
  
  
  CONCLUSIONS
  The onset of menopause is associated with a significant increase in the risk of cardiac events (dominated by recurrent episodes of syncope) in LQT2 women, suggesting that careful follow-up and continued long-term therapy are warranted in this population.
authors.affiliation: Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Buber
authors.forename: Jehu
authors.initials: J
authors.lastname: Mathew
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: W Jackson
authors.initials: WJ
authors.lastname: Hall
authors.forename: Alon
authors.initials: A
authors.lastname: Barsheshet
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Robinson
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Kaufman
authors.forename: David
authors.initials: D
authors.lastname: Luria
authors.forename: Michael
authors.initials: M
authors.lastname: Eldar
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: Michael
authors.initials: M
authors.lastname: Vincent
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
mesh_terms: D000328:Adult; D017677:Age Distribution; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D000072237:ERG1 Potassium Channel; D015914:Estrogen Replacement Therapy / Q000706:statistics & numerical data; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D029593:Jervell-Lange Nielsen Syndrome / Q000235:genetics / Q000401:mortality*; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008593:Menopause; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D029597:Romano-Ward Syndrome / Q000235:genetics / Q000401:mortality*; D013575:Syncope / Q000235:genetics / Q000401:mortality
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human