Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium - PubMed (original) (raw)

Meta-Analysis

. 2017 Feb 16;12(2):e0170791.

doi: 10.1371/journal.pone.0170791. eCollection 2017.

Rolf Jorde 2, Guri Grimnes 2, Ragnar Joakimsen 2, Henrik Schirmer 3, Tom Wilsgaard 4, Ellisiv B Mathiesen 2, Inger Njølstad 4, Maja-Lisa Løchen 4, Winfried März 5 6 7, Marcus E Kleber 5 8, Andreas Tomaschitz 9 10 11, Martin Grübler 1 9 12, Gudny Eiriksdottir 13, Elias F Gudmundsson 13, Tamara B Harris 14, Mary F Cotch 15, Thor Aspelund 13 16, Vilmundur Gudnason 13 16, Femke Rutters 17, Joline W J Beulens 17 18, Esther van 't Riet 17, Giel Nijpels 17, Jacqueline M Dekker 17, Diana Grove-Laugesen 19, Lars Rejnmark 19, Markus A Busch 20, Gert B M Mensink 20, Christa Scheidt-Nave 20, Michael Thamm 20, Karin M A Swart 17, Ingeborg A Brouwer 21, Paul Lips 22, Natasja M van Schoor 17, Christopher T Sempos 23, Ramón A Durazo-Arvizu 24, Zuzana Škrabáková 25, Kirsten G Dowling 25, Kevin D Cashman 25 26, Mairead Kiely 25 27, Stefan Pilz 1 17

Affiliations

Meta-Analysis

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

Martin Gaksch et al. PLoS One. 2017.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1

Fig 1. Dose-response trend of hazard ratios of death from all causes by standardized 25-hydroxyvitamin D.

Dose-response trend of hazard ratios of all-cause mortality by standardized 25-hydroxyvitamin D were adjusted for age, sex, body mass index and season of blood drawing concentrations. Hazard ratios [blue line with 95% confidence interval as the dotted blue lines] are referring to the 25-hydroxyvitamin D concentration of 83.4 nmol/L (i.e. the median 25-hydroxyvitamin D concentration for the group with 25-hydroxyvitamin D concentrations from 75 to 99.99 nmol/L).

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