A prospective evaluation of the risk of QT prolongation with hormone replacement therapy

The atherosclerosis risk in communities study

Mercedes R. Carnethon, Mary S. Anthony, Wayne E. Cascio, Aaron R. Folsom, Pentti M. Rautaharju, Duanping Liao, Gregory W. Evans, Gerardo Heiss

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

PURPOSE: 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 = 3,103) 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 ≥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.

Original languageEnglish (US)
Pages (from-to)530-536
Number of pages7
JournalAnnals of Epidemiology
Volume13
Issue number7
DOIs
StatePublished - Jan 1 2003

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Hormone Replacement Therapy
Atherosclerosis
Estrogen Replacement Therapy
Estrogens
Heart Rate
Progestins
Androgens
Observational Studies
Coronary Disease
Cardiac Arrhythmias
Odds Ratio
Confidence Intervals
Mortality
Population

All Science Journal Classification (ASJC) codes

  • Epidemiology

Cite this

Carnethon, Mercedes R. ; Anthony, Mary S. ; Cascio, Wayne E. ; Folsom, Aaron R. ; Rautaharju, Pentti M. ; Liao, Duanping ; Evans, Gregory W. ; Heiss, Gerardo. / A prospective evaluation of the risk of QT prolongation with hormone replacement therapy : The atherosclerosis risk in communities study. In: Annals of Epidemiology. 2003 ; Vol. 13, No. 7. pp. 530-536.
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A prospective evaluation of the risk of QT prolongation with hormone replacement therapy : The atherosclerosis risk in communities study. / Carnethon, Mercedes R.; Anthony, Mary S.; Cascio, Wayne E.; Folsom, Aaron R.; Rautaharju, Pentti M.; Liao, Duanping; Evans, Gregory W.; Heiss, Gerardo.

In: Annals of Epidemiology, Vol. 13, No. 7, 01.01.2003, p. 530-536.

Research output: Contribution to journalArticle

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T1 - A prospective evaluation of the risk of QT prolongation with hormone replacement therapy

T2 - The atherosclerosis risk in communities study

AU - Carnethon, Mercedes R.

AU - Anthony, Mary S.

AU - Cascio, Wayne E.

AU - Folsom, Aaron R.

AU - Rautaharju, Pentti M.

AU - Liao, Duanping

AU - Evans, Gregory W.

AU - Heiss, Gerardo

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N2 - PURPOSE: 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 = 3,103) 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 ≥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.

AB - PURPOSE: 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 = 3,103) 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 ≥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.

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