Prevalence and effects of functional vitamin K insufficiency : The PREVEND study

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

Vitamin K Dependent Protection of Renal Function in Multi-ethnic Population Studies

Background: Following activation by vitamin K (VK), matrix Gla protein (MGP) inhibits arterial calcification, but its role in preserving renal function remains unknown. Methods: In 1166 white Flemish (mean age, 38.2 years) and 714 South Africans (49.2% black; 40.6 years), we correlated estimated glomerular filtration (eGFR [CKD-EPI formula]) and stage of chronic kidney disease (CKD [KDOQI stages 2–3]) with inactive desphospho-uncarboxylated MGP (dp-ucMGP), using multivariable linear and logistic regression. Results: Among Flemish and white and black Africans, between-group differences in eGFR (90, 100 and 122 mL/min/1.73 m2), dp-ucMGP (3.7, 6.5 and 3.2 μg/L), and CKD prevalence (53.5, 28.7 and 10.5%) were significant, but associations of eGFR with dp-ucMGP did not differ among ethnicities (P ≥ 0.075). For a doubling of dp-ucMGP, eGFR decreased by 1.5 (P = 0.023), 1.0 (P = 0.56), 2.8 (P = 0.0012) and 2.1 (P < 0.0001) mL/min/1.73 m2 in Flemish, white Africans, black Africans and all participants combined; the odds ratios for moving up one CKD stage were 1.17 (P = 0.033), 1.03 (P = 0.87), 1.29 (P = 0.12) and 1.17 (P = 0.011), respectively. Interpretation: In the general population, eGFR decreases and CKD risk increases with higher dp-ucMGP, a marker of VK deficiency. These findings highlight the possibility that VK supplementation might promote renal health