A prospective evaluation of the risk of QT prolongation with hormone replacement therapy: the atherosclerosis risk in communities study.
OBJECTIVE
Prolongation of the QT interval is associated with an increased risk of arrhythmia, coronary heart disease (CHD), and mortality. Estrogens and androgens have been proposed as a causal factor in QT lengthening. We tested whether postmenopausal hormone replacement therapy was associated with prolonged QT intervals in a healthy population sample of women (mean age=54).


METHODS
Women (n=3103) were asked about estrogen (ERT) and progestin plus estrogen (PERT) replacement therapy use at 4 examinations over 9 years. Electrocardiographic QT intervals were measured and corrected for heart rate using the QT Index (QTI) and Bazett's correction. QT prolongation was defined as QTI>110% and a change from baseline of >or=4%.


RESULTS
Heart rate corrected QT length was moderately but significantly (p<0.01) greater, and the risk of QT prolongation was nearly twice (Odds Ratio=1.9, 95% Confidence Interval: 1.2-2.0) that in women who used ERT compared with never users. PERT use was not significantly associated with QT length.


CONCLUSIONS
The potential for slight increases in QT length over time, and an increased risk of QT prolongation with ERT use identified in this observational study, are important concerns that should be further explored in randomized trials.
Carnethon
Mercedes R
MR
Stanford Center for Research in Disease Prevention, Stanford University School of Medicine, Palo Alto, CA, USA. carnethon@northwestern.edu
Anthony
Mary S
MS
Cascio
Wayne E
WE
Folsom
Aaron R
AR
Rautaharju
Pentti M
PM
Liao
Duanping
D
Evans
Gregory W
GW
Heiss
Gerardo
G
D001161:Arteriosclerosis / Q000209:etiology; D015331:Cohort Studies; D004562:Electrocardiography; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D008137:Longitudinal Studies; D008875:Middle Aged; D011446:Prospective Studies; D014481:United States