Prevalence and Effects of Functional Vitamin K Insufficiency: The PREVEND Study

• Published in: Nutrients Vol. 9; no. 12; p. 1334
• Main Authors: Riphagen, Ineke, Keyzer, Charlotte, Drummen, Nadja, De Borst, Martin, Beulens, Joline, Gansevoort, Ron, Geleijnse, Johanna, Muskiet, Frits, Navis, Gerjan, Visser, Sipke, Vermeer, Cees, Kema, Ido, Bakker, Stephan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.12.2017; MDPI
• Subjects: Adult; Aged; All-cause mortality; Biomarkers - blood; calcification; Calcium-Binding Proteins - metabolism; Cardiovascular Diseases - blood; Cardiovascular Diseases - mortality; Cardiovascular mortality; Cohort Studies; comorbidity; confidence interval; elderly; Extracellular Matrix Proteins - metabolism; Female; Health risk assessment; Humans; hypertension; kidney diseases; Male; males; Matrix Gla Protein; Middle Aged; mortality; Netherlands - epidemiology; noninsulin-dependent diabetes mellitus; Risk Factors; tissues; Vitamin K; Vitamin K Deficiency - blood; Vitamin K Deficiency - epidemiology; cardiovascular mortality; matrix Gla protein; vitamin K; all-cause mortality
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu9121334

Matrix Gla Protein (MGP) is a strong vitamin K-dependent inhibitor of soft tissue calcification. We assessed the prevalence of functional vitamin K insufficiency, as derived from plasma desphospho-uncarboxylated MGP (dp-ucMGP), and investigated whether plasma dp-ucMGP is associated with all-cause and cardiovascular mortality in a large general population-based cohort. We included 4275 subjects (aged 53 ± 12 years, 46.0% male) participating in the prospective general population-based Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. The prevalence of functional vitamin K insufficiency (i.e., dp-ucMGP > 500 pmol/L) was 31% in the total study population. This prevalence was significantly higher among elderly and subjects with comorbidities like hypertension, type 2 diabetes, chronic kidney disease, and cardiovascular disease (~50%). After 10 years of follow-up, 279 subjects had died, with 74 deaths attributable to cardiovascular causes. We found significant J-shaped associations of plasma dp-ucMGP with all-cause (linear term: hazard ratio (HR) (95% confidence interval (CI)) = 0.20 (0.12–0.33), p < 0.001; squared term: 1.14 (1.10–1.17), p < 0.001) and cardiovascular mortality (linear term: 0.12 (0.05–0.27), p < 0.001; squared term: 1.17 (1.11–1.23), p < 0.001). These associations remained significant after adjustment for potential confounders. Whether the correction of vitamin K insufficiency improves health outcomes needs to be addressed in future prospective intervention studies.