Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study.
Am J Clin Nutr. 2013 Feb 27.
Schöttker B, Haug U, Schomburg L, Köhrle J, Perna L, Müller H, Holleczek B, Brenner H.
Divisions of Clinical Epidemiology and Aging Research and Preventive Oncology, German Cancer Research Center, Heidelberg, Germany.
BACKGROUND: Serum 25-hydroxyvitamin D [25(OH)D] concentration has been linked to mortality in several studies, but appropriate cutoffs to define risk categories are under debate.
OBJECTIVE: We aimed to conduct a repeated-measurements analysis on the association of serum 25(OH)D concentrations with all-cause and cause-specific mortality, with particular attention given to the shape of dose-response relations.
DESIGN: Concentrations of 25(OH)D were measured in n = 9578 baseline and n = 5469 5-y follow-up participants of the ESTHER study, which is a German population-based cohort aged 50-74 y at baseline. Deaths were recorded during 9.5 y of follow-up (median). Restricted cubic splines were used to assess dose-response relations and Cox regression with time-dependent variables to estimate hazard ratios.
RESULTS: During follow-up, 1083 study participants died, of whom 350 individuals died of cardiovascular diseases, 433 individuals died of cancer, and 55 individuals died of respiratory diseases. The overall mortality [HR (95% CI)] of subjects with vitamin D deficiency [25(OH)D concentrations <30 nmol/L] or vitamin D insufficiency [25(OH)D concentrations from 30 to 50 nmol/L) was significantly increased [[1.71 (1.43, 2.03) and 1.17 (1.02, 1.35), respectively] compared with that of subjects with sufficient 25(OH)D concentrations (>50 nmol/L)].
Vitamin D deficiency was also associated with increased
- cardiovascular mortality [1.39 (95% CI: 1.02, 1.89)],
- cancer mortality [1.42 (95% CI: 1.08, 1.88)] and
- respiratory disease mortality [2.50 (95% CI: 1.12, 5.56)].
The association of 25(OH)D concentrations with all-cause mortality proved to be a nonlinear inverse association with risk that started to increase at 25(OH)D concentrations <75 nmol/L.
CONCLUSIONS: In this large cohort study, serum 25(OH)D concentrations were inversely associated with all-cause and cause-specific mortality. In particular, vitamin D deficiency [25(OH)D concentration <30 nmol/L] was strongly associated with mortality from all causes, cardiovascular diseases, cancer, and respiratory diseases.
of increased risk of death a decade later if < 8 ng.
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