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(Circulation. 2007;115:846-854.)
© 2007 American Heart Association, Inc.

Cardiovascular Disease in Women

Calcium/Vitamin D Supplementation and Cardiovascular Events

Judith Hsia, MD; Gerardo Heiss, MD, PhD; Hong Ren, MS; Matthew Allison, MD, MPH; Nancy C. Dolan, MD; Philip Greenland, MD; Susan R. Heckbert, MD, PhD; Karen C. Johnson, MD, MPH; JoAnn E. Manson, MD, DrPH; Stephen Sidney, MD, MPH; Maurizio Trevisan, PhD, for the Women’s Health Initiative Investigators

From the Department of Medicine, George Washington University, Washington, DC (J.H.); Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill (G.H.); Fred Hutchinson Cancer Research Center, Seattle, Wash (H.R.); Department of Family and Preventive Medicine, University of California at San Diego, San Diego (M.A.); Departments of Medicine (N.C.D., P.G.) and Preventive Medicine (P.G.), Northwestern University, Chicago, Ill; Department of Epidemiology, University of Washington, Seattle (S.R.H.); Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis (K.C.J.); Division of Preventive Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (J.E.M.); Kaiser Permanente, Oakland, Calif (S.S.); and University at Buffalo School of Public Health and Health Professions, Buffalo, NY (M.T.).

Correspondence to Judith Hsia, MD, 2150 Pennsylvania Ave, NW No. 4–414, Washington, DC 20037. E-mail jhsia{at}mfa.gwu.edu

Received November 2, 2006; accepted December 14, 2006.

Background— Individuals with vascular or valvular calcification are at increased risk for coronary events, but the relationship between calcium consumption and cardiovascular events is uncertain. We evaluated the risk of coronary and cerebrovascular events in the Women’s Health Initiative randomized trial of calcium plus vitamin D supplementation.

Methods and Results— We randomized 36 282 postmenopausal women 50 to 79 years of age at 40 clinical sites to calcium carbonate 500 mg with vitamin D 200 IU twice daily or to placebo. Cardiovascular disease was a prespecified secondary efficacy outcome. During 7 years of follow-up, myocardial infarction or coronary heart disease death was confirmed for 499 women assigned to calcium/vitamin D and 475 women assigned to placebo (hazard ratio, 1.04; 95% confidence interval, 0.92 to 1.18). Stroke was confirmed among 362 women assigned to calcium/vitamin D and 377 assigned to placebo (hazard ratio, 0.95; 95% confidence interval, 0.82 to 1.10). In subgroup analyses, women with higher total calcium intake (diet plus supplements) at baseline were not at higher risk for coronary events (P=0.91 for interaction) or stroke (P=0.14 for interaction) if assigned to active calcium/vitamin D.

Conclusions— Calcium/vitamin D supplementation neither increased nor decreased coronary or cerebrovascular risk in generally healthy postmenopausal women over a 7-year use period.

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