Estrogen therapy and coronary-artery calcification

Jo Ann E. Manson, Matthew A. Allison, Jacques E. Rossouw, J. Jeffrey Carr, Robert D. Langer, Judith Hsia, Lewis H. Kuller, Barbara B. Cochrane, Julie R. Hunt, Shari E. Ludlam, Mary B. Pettinger, Margery Gass, Karen L. Margolis, Lauren Nathan, Judith K. Ockene, Ross L. Prentice, John A Robbins, Marcia L. Stefanick

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Abstract

BACKGROUND: Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial. METHODS: In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status. RESULTS: The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P = 0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P = 0.01), 0.55 (P<0.001), and 0.46 (P = 0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P = 0.03) in an intention-to-treat analysis and 0.39 (P = 0.004) among women with at least 80% adherence. CONCLUSIONS: Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways.

Original languageEnglish (US)
Pages (from-to)2591-2602
Number of pages12
JournalNew England Journal of Medicine
Volume356
Issue number25
DOIs
StatePublished - Jun 21 2007

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Coronary Vessels
Estrogens
Placebos
Calcium
Random Allocation
Odds Ratio
Therapeutics
Conjugated (USP) Estrogens
Intention to Treat Analysis
Women's Health
Atherosclerotic Plaques
Hysterectomy
Reading
Randomized Controlled Trials
Tomography
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Manson, J. A. E., Allison, M. A., Rossouw, J. E., Carr, J. J., Langer, R. D., Hsia, J., ... Stefanick, M. L. (2007). Estrogen therapy and coronary-artery calcification. New England Journal of Medicine, 356(25), 2591-2602. https://doi.org/10.1056/NEJMoa071513

Estrogen therapy and coronary-artery calcification. / Manson, Jo Ann E.; Allison, Matthew A.; Rossouw, Jacques E.; Carr, J. Jeffrey; Langer, Robert D.; Hsia, Judith; Kuller, Lewis H.; Cochrane, Barbara B.; Hunt, Julie R.; Ludlam, Shari E.; Pettinger, Mary B.; Gass, Margery; Margolis, Karen L.; Nathan, Lauren; Ockene, Judith K.; Prentice, Ross L.; Robbins, John A; Stefanick, Marcia L.

In: New England Journal of Medicine, Vol. 356, No. 25, 21.06.2007, p. 2591-2602.

Research output: Contribution to journalArticle

Manson, JAE, Allison, MA, Rossouw, JE, Carr, JJ, Langer, RD, Hsia, J, Kuller, LH, Cochrane, BB, Hunt, JR, Ludlam, SE, Pettinger, MB, Gass, M, Margolis, KL, Nathan, L, Ockene, JK, Prentice, RL, Robbins, JA & Stefanick, ML 2007, 'Estrogen therapy and coronary-artery calcification', New England Journal of Medicine, vol. 356, no. 25, pp. 2591-2602. https://doi.org/10.1056/NEJMoa071513
Manson JAE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J et al. Estrogen therapy and coronary-artery calcification. New England Journal of Medicine. 2007 Jun 21;356(25):2591-2602. https://doi.org/10.1056/NEJMoa071513
Manson, Jo Ann E. ; Allison, Matthew A. ; Rossouw, Jacques E. ; Carr, J. Jeffrey ; Langer, Robert D. ; Hsia, Judith ; Kuller, Lewis H. ; Cochrane, Barbara B. ; Hunt, Julie R. ; Ludlam, Shari E. ; Pettinger, Mary B. ; Gass, Margery ; Margolis, Karen L. ; Nathan, Lauren ; Ockene, Judith K. ; Prentice, Ross L. ; Robbins, John A ; Stefanick, Marcia L. / Estrogen therapy and coronary-artery calcification. In: New England Journal of Medicine. 2007 ; Vol. 356, No. 25. pp. 2591-2602.
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abstract = "BACKGROUND: Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial. METHODS: In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status. RESULTS: The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P = 0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95{\%} confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80{\%} adherence to the study estrogen or placebo were 0.64 (P = 0.01), 0.55 (P<0.001), and 0.46 (P = 0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P = 0.03) in an intention-to-treat analysis and 0.39 (P = 0.004) among women with at least 80{\%} adherence. CONCLUSIONS: Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways.",
author = "Manson, {Jo Ann E.} and Allison, {Matthew A.} and Rossouw, {Jacques E.} and Carr, {J. Jeffrey} and Langer, {Robert D.} and Judith Hsia and Kuller, {Lewis H.} and Cochrane, {Barbara B.} and Hunt, {Julie R.} and Ludlam, {Shari E.} and Pettinger, {Mary B.} and Margery Gass and Margolis, {Karen L.} and Lauren Nathan and Ockene, {Judith K.} and Prentice, {Ross L.} and Robbins, {John A} and Stefanick, {Marcia L.}",
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T1 - Estrogen therapy and coronary-artery calcification

AU - Manson, Jo Ann E.

AU - Allison, Matthew A.

AU - Rossouw, Jacques E.

AU - Carr, J. Jeffrey

AU - Langer, Robert D.

AU - Hsia, Judith

AU - Kuller, Lewis H.

AU - Cochrane, Barbara B.

AU - Hunt, Julie R.

AU - Ludlam, Shari E.

AU - Pettinger, Mary B.

AU - Gass, Margery

AU - Margolis, Karen L.

AU - Nathan, Lauren

AU - Ockene, Judith K.

AU - Prentice, Ross L.

AU - Robbins, John A

AU - Stefanick, Marcia L.

PY - 2007/6/21

Y1 - 2007/6/21

N2 - BACKGROUND: Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial. METHODS: In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status. RESULTS: The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P = 0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P = 0.01), 0.55 (P<0.001), and 0.46 (P = 0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P = 0.03) in an intention-to-treat analysis and 0.39 (P = 0.004) among women with at least 80% adherence. CONCLUSIONS: Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways.

AB - BACKGROUND: Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial. METHODS: In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status. RESULTS: The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P = 0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P = 0.01), 0.55 (P<0.001), and 0.46 (P = 0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P = 0.03) in an intention-to-treat analysis and 0.39 (P = 0.004) among women with at least 80% adherence. CONCLUSIONS: Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways.

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