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Thromb Haemost 2015; 113(05): 999-1009
DOI: 10.1160/TH14-05-0478
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The effect of calcium plus vitamin D supplementation on the risk of venous thromboembolism

From the Women’s Health Initiative Randomized Controlled Trial
Marc Blondon
1   Department of Epidemiology, University of Washington, Seattle, Washington, USA
2   Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA
15   Division of Angiology and Haemostasis, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland
,
Rebecca J. Rodabough
5   Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
,
Nicole Budrys
6   Henry Ford Health System, Detroit, Michigan, USA
,
Karen C. Johnson
7   Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA
,
Jeffrey S. Berger
8   Department of Medicine, Marc and Ruti Bell Program in Vascular Biology, New York University School of Medicine, New York, New York, USA
,
James M. Shikany
9   Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
,
Azad Raiesdana
10   Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA
,
Susan R Heckbert
1   Department of Epidemiology, University of Washington, Seattle, Washington, USA
2   Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA
13   Group Health Research Institute, Group Health Cooperative, Seattle, USA
,
JoAnn E. Manson
11   Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
,
Andrea Z. LaCroix
12   Division of Epidemiology, Family and Preventive Medicine, University of California at San Diego, California, USA
,
David Siscovick
16   The New York Academy of Medicine, New York, New York, USA
,
Bryan Kestenbaum
1   Department of Epidemiology, University of Washington, Seattle, Washington, USA
3   Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington, USA
4   Department of Medicine, University of Washington, Seattle, Washington, USA
,
Nicholas L. Smith
1   Department of Epidemiology, University of Washington, Seattle, Washington, USA
2   Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA
13   Group Health Research Institute, Group Health Cooperative, Seattle, USA
14   Seattle Epidemiologic Research and information Center, Department of Veterans Affairs Office of Research and Development, Seattle, Washington, USA
,
Ian H. de Boer
1   Department of Epidemiology, University of Washington, Seattle, Washington, USA
3   Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington, USA
› Author Affiliations
Further Information

Publication History

Received: 30 May 2014

Accepted after major revision: 18 February 2014

Publication Date:
24 November 2017 (online)

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Summary

Experimental and epidemiological studies suggest that vitamin D may be implicated in haemostatic regulations and influence the risk of venous thromboembolism (VTE). The aim of this study was to investigate whether oral supplementation of vitamin D3 combined with calcium reduces the risk of VTE. In the randomised, double-blind, placebo-controlled Women’s Health Initiative Calcium Plus Vitamin D trial, 36,282 postmenopausal women aged 50-79 years were randomised to receive 1,000 mg of calcium carbonate and 400 IU of vitamin D3 per day (n=18,176) or a matching placebo (n=18,106) during an average of seven years. This secondary analysis of the trial compared the incidence of VTE by treatment group using an intention-to-treat Cox regression analysis. The incidence of VTE did not differ between women randomised to calcium plus vitamin D and women randomised to placebo (320 vs 348 VTE events, respectively; hazard ratio (HR) 0.92, 95 % confidence interval (CI) 0.79-1.07). Results were not modified in an analysis using inverse-probability weights to take non-adherence into account (HR 0.94, 95 %CI 0.73-1.22) or in multiple subgroups. Whereas the risk of a non-idiopathic VTE was similar between groups, the risk of idiopathic VTE was lower in women randomised to calcium plus vitamin D (40 vs 65 events; HR 0.62, 95 %CI 0.42-0.92). In conclusion, daily supplementation with 1,000 mg of calcium and 400 IU of vitamin D did not reduce the overall incidence of VTE in generally healthy postmenopausal women. However, the observed reduced risk of idiopathic VTE in women randomised to calcium and vitamin D warrants further investigations.

Trial Registration: NCT00000611 (www.clinicaltrials.gov).

Keywords

Venous thrombosis - risk factors - clinical studies