Combined low vitamin D and K status amplifies mortality risk: a prospective study

Adriana J. van Ballegooijen, Joline W.J. Beulens, Lyanne M. Kieneker, Martin H. de Borst, Ron T. Gansevoort, Ido P. Kema, Leon J. Schurgers, Marc G. Vervloet, Stephan J.L. Bakker

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9 Citations (Scopus)


Objective: To explore the association of both plasma vitamin D and K concentrations with all-cause mortality, cardiovascular mortality, and cardiovascular events in the general population. Methods: We studied 4742 participants of the Prevention of REnal and Vascular ENd-Stage Disease (PREVEND) Study. At baseline, vitamin D and K status was determined by measurement of 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), respectively. Patients were categorized into: 25(OH)D < 50 or ≥ 50 nmol/L and dp-ucMGP < 361 or ≥ 361 pmol/L with 25(OH)D > 75 nmol/L and dp-ucMGP < 361 pmol/L as reference. Cause of death was coded according to International Classification of Diseases 9&10 codes from the 2001-2003 examination until date of death/event or censoring date (January 1st, 2017). Results: Mean age was 52.6 ± 11.9 years and 2513 (53%) were female. During a median of 14.2 year follow-up, 620 participants died of which 142 were due to cardiovascular causes. Combined low vitamin D and K status was present in 970 participants (20%) and was associated with a greater risk of all-cause mortality compared to high vitamin D and high vitamin K status group (n = 1424) after adjusting for potential confounders: hazard ratio 1.46 (95% confidence intervals 1.12–1.90). We observed similar trends, albeit non-significant for cardiovascular mortality, and cardiovascular events: 1.42 (0.79–2.55), 1.28 (0.93–1.77), respectively. Conclusions: Combined low vitamin D and K status are associated with increased all-cause mortality risk and possibly with cardiovascular mortality and cardiovascular events compared with adequate vitamin D and K status. Future studies should investigate the effect of combined vitamin D and K supplementation on clinical outcomes.

Original languageEnglish
Pages (from-to)1645-1654
Number of pages10
JournalEuropean Journal of Nutrition
Issue number3
Publication statusPublished - Apr 2021


  • All-cause mortality
  • Cardiovascular mortality
  • Vitamin D
  • Vitamin K

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