Menopause: The Journal of The North American Menopause Society Vol. 21, No. 8, pp. 823/833 DOI: 10.1097/gme.0000000000000188 * 2014 by The North American Menopause Society

Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women_s Health Initiative calcium/vitamin D randomized trial Peter F. Schnatz, DO, FACP, FACOG, NCMP,1,2,3,4 Xuezhi Jiang, MD, FACOG, NCMP,1,3 Sharon Vila-Wright, MD,1 Aaron K. Aragaki, MS,5 Matthew Nudy, BS,1,3 David M. O’Sullivan, PhD,1 Rebecca Jackson, MD,6 Erin LeBlanc, MD, MPH,7 Jennifer G. Robinson, MD, MPH,8 James M. Shikany, DrPH,9 Catherine R. Womack, MD,10 Lisa W. Martin, MD,11 Marian L. Neuhouser, PhD,5 Mara Z. Vitolins, DrPH, MPH, RD,12 Yiqing Song, MD, ScD,13 Stephen Kritchevsky, PhD,14 and JoAnn E. Manson, MD, DrPH, NCMP13 Abstract Objective: The objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women. Methods: The parent trial was a double-blind, randomized, placebo-controlled, parallel-group trial designed to test the effects of CaD supplementation (1,000 mg of elemental calcium + 400 IU of vitamin D3 daily) versus placebo in postmenopausal women. Women from the general community, including multiple sites in the United States, were enrolled between 1993 and 1998. This cohort included 300 white, 200 African-American, and 100 Hispanic participants who were randomly selected from the Women’s Health Initiative CaD trial. Serum 25OHD3 and lipid (fasting plasma triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], and calculated lowdensity lipoprotein cholesterol [LDL-C]) levels were assessed before and after CaD randomization. Results: There was a 38% increase in mean serum 25OHD3 concentrations after 2 years (95% CI, 1.29-1.47, P G 0.001) for women randomized to CaD (24.3 ng/mL postrandomization mean) compared with placebo (18.2 ng/mL). Women randomized to CaD had a 4.46Ymg/dL mean decrease in LDL-C (P = 0.03). Higher concentrations of 25OHD3 were associated with higher HDL-C levels (P = 0.003), along with lower LDL-C and TG levels (P = 0.02 and P G 0.001, respectively). Conclusions: Supplemental CaD significantly increases 25OHD3 concentrations and decreases LDL-C. Women with higher 25OHD3 concentrations have more favorable lipid profiles, including increased HDL-C, lower LDL-C, and lower TG. These results support the hypothesis that higher concentrations of 25OHD3, in response to CaD supplementation, are associated with improved LDL-C. Key Words: Vitamin D Y Cholesterol Y Coronary artery disease Y Menopause Y Low-density lipoprotein cholesterol.

Received August 16, 2013; revised and accepted November 11, 2013. From the Departments of 1ObGyn and 2Internal Medicine, The Reading Hospital, Reading, PA; Departments of 3ObGyn and 4Internal Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA; 5Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; 6Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH; 7Center for Health Research NW, Kaiser Permanente, Portland, OR; 8Departments of Epidemiology and Medicine, University of Iowa, Iowa City, IA; 9Division of Preventive Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL; 10Department of Preventive Medicine, University of Tennessee, Memphis, TN; 11Division of Cardiology, Department of Internal Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC; 12Department of Epidemiology and Prevention, Wake Forest University, Winston-Salem, NC; 13 Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA; and 14Sticht Center on Aging, Wake Forest University, Winston-Salem, NC.

Funding/support: The research on which this publication was based was supported by grant R01 HL083326 from the National Heart, Lung, and Blood Institute. The WHI program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The research reported in this article was supported by the research budget of the Reading Health System. Clinical trial registration: identifier NCT00000611 (http://clinicaltrials. gov/ct2/show/NCT00000611?term=women%27s+health+initiative& rank=5). Financial disclosure/conflicts of interest: None reported. Address correspondence to: Peter F. Schnatz, DO, FACP, FACOG, NCMP, Department of ObGyn R1, The Reading Hospital, PO Box 16052, Reading, PA 19612-6052. E-mail: [email protected] Menopause, Vol. 21, No. 8, 2014

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ince the association between dyslipidemia and cardiovascular disease in women has been established,1 there have been an increasing number of studies investigating calcium/vitamin D (CaD) and their effects on lipid concentrations.2

vitamin D randomized trial.

The objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (Ca...
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