title: Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study.
abstract: 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.
  
  
  METHODS
  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 was used to estimate hazard ratios.
  
  
  RESULTS
  During follow-up, 1083 study participants died; of those, 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.
authors: Divisions of Clinical Epidemiology and Aging Research and Preventive Oncology, German Cancer Research Center, Heidelberg, Germany. b.schoettker@dkfz.de
authors: Ben
authors: B
authors: Schöttker
authors: Ulrike
authors: U
authors: Haug
authors: Lutz
authors: L
authors: Schomburg
authors: Joseph
authors: J
authors: Köhrle
authors: Laura
authors: L
authors: Perna
authors: Heiko
authors: H
authors: Müller
authors: Bernd
authors: B
authors: Holleczek
authors: Hermann
authors: H
authors: Brenner
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality*; D002423:Cause of Death; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality*; D016016:Proportional Hazards Models; D012140:Respiratory Tract Diseases / Q000401:mortality*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000401:mortality*
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D