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Calcium/vitamin D supplementation and coronary artery calcification in the Women's Health Initiative

Manson, JoAnn E. MD, DrPH1; Allison, Matthew A. MD, MPH2; Carr, J. Jeffrey MD3; Langer, Robert D. MD, MPH4; Cochrane, Barbara B. PhD, RN5; Hendrix, Susan L. DO6; Hsia, Judith MD7; Hunt, Julie R. PhD8; Lewis, Cora E. MD, MSPH9; Margolis, Karen L. MD, MPH10; Robinson, Jennifer G. MD, MPH11; Rodabough, Rebecca J. MS8; Thomas, Asha M. MD12for the Women's Health Initiative and Women's Health Initiative-Coronary Artery Calcium Study Investigators

doi: 10.1097/gme.0b013e3181d683b5

Objective: Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D (calcium/D) supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared CAC scores after trial completion between women randomized to calcium/vitamin D supplementation and women randomized to placebo.

Methods: In an ancillary substudy of women randomized to calcium carbonate (1,000 mg of elemental calcium daily) plus vitamin D3 (400 IU daily) or placebo, nested within the Women's Health Initiative trial of estrogen among women who underwent hysterectomy, we measured CAC with cardiac CT in 754 women aged 50 to 59 years at randomization. Imaging for CAC was performed at 28 of 40 centers after a mean of 7 years of treatment, and scans were read centrally. CAC scores were measured by a central reading center with masking to randomization assignments.

Results: Posttrial CAC measurements were similar in women randomized to calcium/D supplementation and those receiving placebo. The mean CAC score was 91.6 for women receiving calcium/D and 100.5 for women receiving placebo (rank test P value = 0.74). After adjustment for coronary risk factors, multivariate odds ratios for increasing CAC score cutpoints (CAC >0, ≥10, and ≥100) for calcium/D versus placebo were 0.92 (95% CI, 0.64-1.34), 1.29 (0.88-1.87), and 0.90 (0.56-1.44), respectively. Corresponding odds ratios among women with a 50% or higher adherence to study pills and for higher levels of CAC (>300) were similar.

Conclusions: Treatment with moderate doses of calcium plus vitamin D3 did not seem to alter coronary artery calcified plaque burden among postmenopausal women. Whether higher or lower doses would affect this outcome remains uncertain.

Coronary artery-calcified plaque burden is a marker for future risk of cardiovascular events. In the Women's Health Initiative, an intervention including calcium and vitamin D did not seem to alter coronary artery calcification among postmenopausal women.

From the 1Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 2University of California, San Diego, San Diego, CA; 3Wake Forest University School of Medicine, Winston-Salem, NC; 4Jackson Hole Center for Preventive Medicine, Jackson Hole, WY; 5University of Washington, Seattle, WA; 6Hutzel Women's Hospital/Detroit Medical Center, Detroit, MI; 7George Washington University, Washington, DC; 8Fred Hutchinson Cancer Research Center, Seattle, WA; 9University of Alabama at Birmingham, Birmingham, AL; 10HealthPartners Research Foundation and University of Minnesota, Minneapolis, MN; 11University of Iowa, Iowa City, IA; and 12Sinai Hospital of Baltimore, Baltimore, MD and Medstar Research Institute, Washington, DC.

Received August 31, 2009; revised and accepted January 5, 2010.

Funding/support: The National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, funds the Women's Health Initiative program (through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221) and provided support for the Women's Health Initiative-Coronary Artery Calcium Study ancillary study. GlaxoSmithKline provided the calcium/vitamin D study pills (active and placebo) for the trial but had no other role in the study.

Financial disclosure/conflicts of interest: None reported.

Dr. Hsia is currently affiliated with Astra Zeneca, LLP.

*The Women's Health Initiative and Women's Health Initiative-Coronary Artery Calcium Study investigators are listed in the Appendix.

Address correspondence to: JoAnn Manson, MD, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Ave. East, 3rd Floor, Boston, MA 02215. E-mail:

©2010The North American Menopause Society