title: Association of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone with mortality among middle-aged and older European men.
abstract: BACKGROUND
  vitamin D deficiency has been associated with an increased risk of mortality, but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain. Our objective was to determine whether endogenous 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels predicted all-cause, cardiovascular and cancer mortality independently of health and lifestyle factors.
  
  
  METHODS
  : prospective cohort analysis within the European Male Ageing Study.
  
  
  METHODS
  : 2,816 community-dwelling men aged 40-79 years at baseline.
  
  
  METHODS
  : Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)2D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models.
  
  
  RESULTS
  : a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)2D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D <25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04).
  
  
  CONCLUSIONS
  : lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here.
authors.affiliation: Cathie Marsh Centre for Census and Survey Research, School of Social Sciences, The University of Manchester, Manchester, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Lee
authors.affiliation: Andrology and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.affiliation: Geriatric Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: Terence W
authors.initials: TW
authors.lastname: O'Neill
authors.affiliation: Clinical & Cognitive Neurosciences, Institute of Brain, Behaviour and Mental Health, The University of Manchester, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Pendleton
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Pye
authors.affiliation: Andrology Research Unit, Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester, UK.
authors.forename: Rathi
authors.initials: R
authors.lastname: Ravindrarajah
authors.affiliation: Geriatric Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Gielen
authors.affiliation: Molecular Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Claessens
authors.affiliation: Department of Obstetrics, Gynecology and Andrology, Albert Szent-György Medical University, Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Bartfai
authors.affiliation: Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago, CIBER de Fisiopatología Obesidad y Nutricion, Instituto Salud Carlos III, Santiago de Compostela, Spain.
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.affiliation: Andrology Research Unit, Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester, UK.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Finn
authors.affiliation: Endocrinology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Forti
authors.affiliation: Reproductive Medicine Centre, Malmö University Hospital, University of Lund, Malmö, Sweden.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.affiliation: Department of Endocrinology, Royal Free and University College Hospital Medical School, Royal Free Hospital, London, UK.
authors.forename: Thang S
authors.initials: TS
authors.lastname: Han
authors.affiliation: Department of Reproductive Biology, Imperial College London, London, UK.
authors.forename: Ilpo T
authors.initials: IT
authors.lastname: Huhtaniemi
authors.affiliation: Department of Andrology and Reproductive Endocrinology, Medical University of Łódź, Łódź, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kula
authors.affiliation: Division of Developmental Medicine, Human Nutrition Section, University of Glasgow, Glasgow, UK.
authors.forename: Michael E J
authors.initials: ME
authors.lastname: Lean
authors.affiliation: Andrology Unit, United Laboratories of Tartu University Clinics, Tartu, Estonia.
authors.forename: Margus
authors.initials: M
authors.lastname: Punab
authors.affiliation: Andrology Research Unit, Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester, UK.
authors.forename: Frederick C W
authors.initials: FC
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000401:mortality*; D015331:Cohort Studies; D005060:Europe; D005500:Follow-Up Studies; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality*; D010281:Parathyroid Hormone / Q000097:blood*; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D011795:Surveys and Questionnaires; D015996:Survival Rate; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C104450:25-hydroxyvitamin D
keywords: 1,25-dihydroxyvitamin D; 25-hydroxyvitamin D; mortality; older people; parathyroid hormone; population based