Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women's Health Initiative: A Randomized Controlled Trial.
Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women's Health Initiative: A Randomized Controlled Trial.
- 2017
Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611. 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. 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). OBJECTIVE: To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors. 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).
English
0029-7844
*Calcium Carbonate/ad [Administration & Dosage]
*Calcium, Dietary/ad [Administration & Dosage]
*Cholecalciferol/ad [Administration & Dosage]
*Cholesterol, LDL/bl [Blood]
*Estrogen Replacement Therapy
*Vitamins/ad [Administration & Dosage]
Aged
Cardiovascular Diseases/bl [Blood]
Dietary Supplements
Double-Blind Method
Drug Synergism
Drug Therapy, Combination
Estrogens, Conjugated (USP)/tu [Therapeutic Use]
Female
Humans
Medroxyprogesterone Acetate/tu [Therapeutic Use]
Middle Aged
Prospective Studies
Risk Factors
Women's Health
MedStar Health Research Institute
Journal Article
Randomized Controlled Trial
Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611. 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. 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). OBJECTIVE: To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors. 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).
English
0029-7844
*Calcium Carbonate/ad [Administration & Dosage]
*Calcium, Dietary/ad [Administration & Dosage]
*Cholecalciferol/ad [Administration & Dosage]
*Cholesterol, LDL/bl [Blood]
*Estrogen Replacement Therapy
*Vitamins/ad [Administration & Dosage]
Aged
Cardiovascular Diseases/bl [Blood]
Dietary Supplements
Double-Blind Method
Drug Synergism
Drug Therapy, Combination
Estrogens, Conjugated (USP)/tu [Therapeutic Use]
Female
Humans
Medroxyprogesterone Acetate/tu [Therapeutic Use]
Middle Aged
Prospective Studies
Risk Factors
Women's Health
MedStar Health Research Institute
Journal Article
Randomized Controlled Trial