Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women's Health Initiative

Peter F. Schnatz, Xuezhi Jiang, Aaron K. Aragaki, Matthew Nudy, David M. O'Sullivan, Mark Williams, Erin S. Leblanc, Lisa W. Martin, Joann E. Manson, James M. Shikany, Karen Johnson, Marcia L. Stefanick, Martha E. Payne, Jane A. Cauley, Barbara V. Howard, John Robbins

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial among Women's Health Initiative (WHI) participants. The predefined primary outcome was low-density lipoprotein cholesterol (LDL-C). RESULTS: Between September 1993 and October 1998, a total of 68,132 women aged 50-79 years were recruited and randomized to the WHI-Dietary Modification (n=48,835) and WHI-Hormone Therapy trials (n=27,347). Subsequently, 36,282 women from WHI-Hormone Therapy (16,089) and WHI-Dietary Modification (n=25,210) trials were randomized in the WHI-Calcium+Vitamin D trial to 1,000 mg elemental calcium carbonate plus 400 international units vitamin D3 daily or placebo. Our study group included 1,521 women who participated in both the hormone therapy and calcium+vitamin D trials and were in the 6% subsample of trial participants with blood sample collections at baseline and years 1, 3, and 6. The average treatment effect with 95% confidence interval, for LDL-C, compared with placebo, was -1.6, (95% confidence interval [CI] -5.5 to 2.2) mg/dL for calcium+vitamin D alone, -9.0 (95% CI -13.0 to -5.1) mg/dL for hormone therapy alone, and -13.8 (95% CI -17.8 to -9.8) mg/dL for the combination. There was no evidence of a synergistic effect of calcium+vitamin D+hormone therapy on LDL-C (P value for interaction=.26) except in those with low total intakes of vitamin D, for whom there was a significant synergistic effect on LDL (P value for interaction=.03). CONCLUSION: Reductions in LDL-C were greater among women randomized to both calcium+vitamin D and hormone therapy than for those randomized to either intervention alone or to placebo. The treatment effect observed in the calcium+vitamin D+hormone therapy combination group may be additive rather than synergistic. For clinicians and patients deciding to begin calcium+vitamin D supplementation, current use of hormone therapy should not influence that decision. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611.

Original languageEnglish (US)
Pages (from-to)121-129
Number of pages9
JournalObstetrics and gynecology
Volume129
Issue number1
DOIs
StatePublished - Jan 1 2017

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Women's Health
Vitamin D
Cardiovascular Diseases
Hormones
Calcium
LDL Cholesterol
Placebos
Therapeutics
Confidence Intervals
Diet Therapy
Calcium Carbonate
Cholecalciferol
Group Psychotherapy
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Obstetrics and Gynecology

Cite this

Schnatz, P. F., Jiang, X., Aragaki, A. K., Nudy, M., O'Sullivan, D. M., Williams, M., ... Robbins, J. (2017). Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women's Health Initiative. Obstetrics and gynecology, 129(1), 121-129. https://doi.org/10.1097/AOG.0000000000001774

Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women's Health Initiative. / Schnatz, Peter F.; Jiang, Xuezhi; Aragaki, Aaron K.; Nudy, Matthew; O'Sullivan, David M.; Williams, Mark; Leblanc, Erin S.; Martin, Lisa W.; Manson, Joann E.; Shikany, James M.; Johnson, Karen; Stefanick, Marcia L.; Payne, Martha E.; Cauley, Jane A.; Howard, Barbara V.; Robbins, John.

In: Obstetrics and gynecology, Vol. 129, No. 1, 01.01.2017, p. 121-129.

Research output: Contribution to journalArticle

Schnatz, PF, Jiang, X, Aragaki, AK, Nudy, M, O'Sullivan, DM, Williams, M, Leblanc, ES, Martin, LW, Manson, JE, Shikany, JM, Johnson, K, Stefanick, ML, Payne, ME, Cauley, JA, Howard, BV & Robbins, J 2017, 'Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women's Health Initiative', Obstetrics and gynecology, vol. 129, no. 1, pp. 121-129. https://doi.org/10.1097/AOG.0000000000001774
Schnatz, Peter F. ; Jiang, Xuezhi ; Aragaki, Aaron K. ; Nudy, Matthew ; O'Sullivan, David M. ; Williams, Mark ; Leblanc, Erin S. ; Martin, Lisa W. ; Manson, Joann E. ; Shikany, James M. ; Johnson, Karen ; Stefanick, Marcia L. ; Payne, Martha E. ; Cauley, Jane A. ; Howard, Barbara V. ; Robbins, John. / Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women's Health Initiative. In: Obstetrics and gynecology. 2017 ; Vol. 129, No. 1. pp. 121-129.
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abstract = "OBJECTIVE: To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial among Women's Health Initiative (WHI) participants. The predefined primary outcome was low-density lipoprotein cholesterol (LDL-C). RESULTS: Between September 1993 and October 1998, a total of 68,132 women aged 50-79 years were recruited and randomized to the WHI-Dietary Modification (n=48,835) and WHI-Hormone Therapy trials (n=27,347). Subsequently, 36,282 women from WHI-Hormone Therapy (16,089) and WHI-Dietary Modification (n=25,210) trials were randomized in the WHI-Calcium+Vitamin D trial to 1,000 mg elemental calcium carbonate plus 400 international units vitamin D3 daily or placebo. Our study group included 1,521 women who participated in both the hormone therapy and calcium+vitamin D trials and were in the 6{\%} subsample of trial participants with blood sample collections at baseline and years 1, 3, and 6. The average treatment effect with 95{\%} confidence interval, for LDL-C, compared with placebo, was -1.6, (95{\%} confidence interval [CI] -5.5 to 2.2) mg/dL for calcium+vitamin D alone, -9.0 (95{\%} CI -13.0 to -5.1) mg/dL for hormone therapy alone, and -13.8 (95{\%} CI -17.8 to -9.8) mg/dL for the combination. There was no evidence of a synergistic effect of calcium+vitamin D+hormone therapy on LDL-C (P value for interaction=.26) except in those with low total intakes of vitamin D, for whom there was a significant synergistic effect on LDL (P value for interaction=.03). CONCLUSION: Reductions in LDL-C were greater among women randomized to both calcium+vitamin D and hormone therapy than for those randomized to either intervention alone or to placebo. The treatment effect observed in the calcium+vitamin D+hormone therapy combination group may be additive rather than synergistic. For clinicians and patients deciding to begin calcium+vitamin D supplementation, current use of hormone therapy should not influence that decision. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611.",
author = "Schnatz, {Peter F.} and Xuezhi Jiang and Aragaki, {Aaron K.} and Matthew Nudy and O'Sullivan, {David M.} and Mark Williams and Leblanc, {Erin S.} and Martin, {Lisa W.} and Manson, {Joann E.} and Shikany, {James M.} and Karen Johnson and Stefanick, {Marcia L.} and Payne, {Martha E.} and Cauley, {Jane A.} and Howard, {Barbara V.} and John Robbins",
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T1 - Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women's Health Initiative

AU - Schnatz, Peter F.

AU - Jiang, Xuezhi

AU - Aragaki, Aaron K.

AU - Nudy, Matthew

AU - O'Sullivan, David M.

AU - Williams, Mark

AU - Leblanc, Erin S.

AU - Martin, Lisa W.

AU - Manson, Joann E.

AU - Shikany, James M.

AU - Johnson, Karen

AU - Stefanick, Marcia L.

AU - Payne, Martha E.

AU - Cauley, Jane A.

AU - Howard, Barbara V.

AU - Robbins, John

PY - 2017/1/1

Y1 - 2017/1/1

N2 - OBJECTIVE: To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial among Women's Health Initiative (WHI) participants. The predefined primary outcome was low-density lipoprotein cholesterol (LDL-C). RESULTS: Between September 1993 and October 1998, a total of 68,132 women aged 50-79 years were recruited and randomized to the WHI-Dietary Modification (n=48,835) and WHI-Hormone Therapy trials (n=27,347). Subsequently, 36,282 women from WHI-Hormone Therapy (16,089) and WHI-Dietary Modification (n=25,210) trials were randomized in the WHI-Calcium+Vitamin D trial to 1,000 mg elemental calcium carbonate plus 400 international units vitamin D3 daily or placebo. Our study group included 1,521 women who participated in both the hormone therapy and calcium+vitamin D trials and were in the 6% subsample of trial participants with blood sample collections at baseline and years 1, 3, and 6. The average treatment effect with 95% confidence interval, for LDL-C, compared with placebo, was -1.6, (95% confidence interval [CI] -5.5 to 2.2) mg/dL for calcium+vitamin D alone, -9.0 (95% CI -13.0 to -5.1) mg/dL for hormone therapy alone, and -13.8 (95% CI -17.8 to -9.8) mg/dL for the combination. There was no evidence of a synergistic effect of calcium+vitamin D+hormone therapy on LDL-C (P value for interaction=.26) except in those with low total intakes of vitamin D, for whom there was a significant synergistic effect on LDL (P value for interaction=.03). CONCLUSION: Reductions in LDL-C were greater among women randomized to both calcium+vitamin D and hormone therapy than for those randomized to either intervention alone or to placebo. The treatment effect observed in the calcium+vitamin D+hormone therapy combination group may be additive rather than synergistic. For clinicians and patients deciding to begin calcium+vitamin D supplementation, current use of hormone therapy should not influence that decision. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611.

AB - OBJECTIVE: To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial among Women's Health Initiative (WHI) participants. The predefined primary outcome was low-density lipoprotein cholesterol (LDL-C). RESULTS: Between September 1993 and October 1998, a total of 68,132 women aged 50-79 years were recruited and randomized to the WHI-Dietary Modification (n=48,835) and WHI-Hormone Therapy trials (n=27,347). Subsequently, 36,282 women from WHI-Hormone Therapy (16,089) and WHI-Dietary Modification (n=25,210) trials were randomized in the WHI-Calcium+Vitamin D trial to 1,000 mg elemental calcium carbonate plus 400 international units vitamin D3 daily or placebo. Our study group included 1,521 women who participated in both the hormone therapy and calcium+vitamin D trials and were in the 6% subsample of trial participants with blood sample collections at baseline and years 1, 3, and 6. The average treatment effect with 95% confidence interval, for LDL-C, compared with placebo, was -1.6, (95% confidence interval [CI] -5.5 to 2.2) mg/dL for calcium+vitamin D alone, -9.0 (95% CI -13.0 to -5.1) mg/dL for hormone therapy alone, and -13.8 (95% CI -17.8 to -9.8) mg/dL for the combination. There was no evidence of a synergistic effect of calcium+vitamin D+hormone therapy on LDL-C (P value for interaction=.26) except in those with low total intakes of vitamin D, for whom there was a significant synergistic effect on LDL (P value for interaction=.03). CONCLUSION: Reductions in LDL-C were greater among women randomized to both calcium+vitamin D and hormone therapy than for those randomized to either intervention alone or to placebo. The treatment effect observed in the calcium+vitamin D+hormone therapy combination group may be additive rather than synergistic. For clinicians and patients deciding to begin calcium+vitamin D supplementation, current use of hormone therapy should not influence that decision. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611.

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