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PLoS One. 2017 Feb 16;12(2):e0170791. doi: 10.1371/journal.pone.0170791. eCollection 2017.

Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium.

Author information

  • 1Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
  • 2Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
  • 3Tromsø Cardiovascular Research Group UNN, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
  • 4Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
  • 5Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
  • 6Synlab Academy, Mannheim, Germany.
  • 7Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
  • 8Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany.
  • 9Department of Cardiology, Medical University of Graz, Graz, Austria.
  • 10Specialist Clinic for Rehabilitation Bad Aussee, Bad Aussee, Austria.
  • 11Department of Internal Medicine - Cardiology, Charité University Hospital Berlin, Campus Virchow Klinikum, Berlin, Germany.
  • 12Swiss Cardiovascular Center Bern, Department of Cardiology, Bern University Hospital, Bern, Switzerland.
  • 13Icelandic Heart Association, Kopavogur, Iceland.
  • 14National Institute on Aging, Laboratory of Epidemiology, and Population Sciences, Bethesda, Maryland, United States of America.
  • 15Division of Epidemiology and Clinical Applications, National Eye Institute, Bethesda, Maryland, United States of America.
  • 16Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
  • 17Department of Epidemiology and Biostatistics and EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
  • 18Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
  • 19Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • 20Department of Epidemiology and Health Monitoring, Robert Koch Institute, Berlin, Germany.
  • 21Department of Health Sciences and the EMGO Institute for Health and Care Research, Faculty of Earth and Life Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
  • 22Department of Internal Medicine, Endocrine Section, VU University medical center, Amsterdam, the Netherlands.
  • 23National Institute of Health Office of Dietary Supplements, Bethesda, Maryland, United States of America.
  • 24Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, Illinois, United States of America.
  • 25Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
  • 26Department of Medicine, University College Cork, Cork, Ireland.
  • 27Irish Centre for Fetal and Neonatal Translational Research [INFANT], University College Cork, Cork, Ireland.

Abstract

BACKGROUND:

Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality.

METHODS:

In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488.

FINDINGS:

We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and <30 nmol/L were 1.15 (1.00-1.29), 1.33 (1.16-1.51), and 1.67 (1.44-1.89), respectively. We observed similar results for cardiovascular mortality, but there was no significant linear association between 25(OH)D and cancer mortality. There was also no significantly increased mortality risk at high 25(OH)D levels up to 125 nmol/L.

INTERPRETATION:

In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths.

PMID:
28207791
DOI:
10.1371/journal.pone.0170791
[PubMed - in process]
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