Prospective association of vitamin D concentrations with mortality in postmenopausal women: results from the Women's Health Initiative (WHI)

Background: Prospective epidemiologic data on the association between vitamin D and all-cause and cause-specific mortality are limited. Objective: This study aimed to determine whether 25-hydroxy-vitamin D [25(OH) D] concentrations were prospectively and independently associated with cardiovascular disease (CVD), cancer, and all-cause mortality in postmenopausal women. Design: A substudy in 2429 postmenopausal women within the Women's Health Initiative (WHI) with measured baseline 25(OH) D concentrations were followed for 10 y for death from CVD, cancer, and all-cause mortality. Proportional hazards models were performed to evaluate quartiles of month-adjusted 25(OH) D concentrations, with adjustment for potential confounders. Sequential model building and analysis for multiplicative interaction were performed to evaluate the effects of central adiposity on the association of low 25(OH) D with all-cause mortality. Results: Of the 2429 women, 224 deaths occurred, with 79 deaths from CVD and 62 deaths from cancer. Multivariate-adjusted HRs that compared quartiles 1 (lowest) to 4 (highest) of 25(OH) D for all-cause mortality (HR: 1.25; 95% CI: 0.80, 1.95), CVD mortality (HR: 1.27; 95% CI: 0.81, 1.99), and cancer mortality (HR: 1.39; 95% CI: 0.88, 2.19) were not significant. There was a potential interaction (P = 0.08) between abdominal obesity and low 25(OH) D concentrations that showed an increased risk of the lowest quartile of 25(OH) D concentrations (HR: 1.85; 95% CI: 1.00, 3.44) with increased mortality in women with a normal waist circumference but no increased risk in women with abdominal obesity (HR: 0.96; 95% CI: 0.52, 1.76). Conclusion: Body fat distribution may play an important role in the modulation of the effect of low vitamin D concentrations on health. This trial was registered at clinicaltrials. gov as NCT 00000611. Am J Clin Nutr 2011; 94: 1471-8.