title: The effect of calcium plus vitamin D supplementation on the risk of venous thromboembolism. From the Women's Health Initiative Randomized Controlled Trial.
abstract: 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.
authors: Marc Blondon, Division of Angiology and Haemostasis, Geneva University Hospitals, Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland, Tel.: +41 22 372 29 752, Fax: +41 22 372 98 91, E-mail: marc.blondon@hcuge.ch.
authors: Marc
authors: M
authors: Blondon
authors: Rebecca J
authors: RJ
authors: Rodabough
authors: Nicole
authors: N
authors: Budrys
authors: Karen C
authors: KC
authors: Johnson
authors: Jeffrey S
authors: JS
authors: Berger
authors: James M
authors: JM
authors: Shikany
authors: Azad
authors: A
authors: Raiesdana
authors: Susan R
authors: SR
authors: Heckbert
authors: JoAnn E
authors: JE
authors: Manson
authors: Andrea Z
authors: AZ
authors: LaCroix
authors: David
authors: D
authors: Siscovick
authors: Bryan
authors: B
authors: Kestenbaum
authors: Nicholas L
authors: NL
authors: Smith
authors: Ian H
authors: IH
authors: de Boer
mesh_terms: D000284:Administration, Oral; D000368:Aged; D002119:Calcium Carbonate / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000150:complications; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006620:Hip Fractures / Q000150:complications; D006801:Humans; D008875:Middle Aged; D016016:Proportional Hazards Models; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000150:complications / Q000517:prevention & control*; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D014807:Vitamin D; D002119:Calcium Carbonate
keywords: Venous thrombosis; clinical studies; risk factors