Prevalence and Effects of Functional Vitamin K Insufficiency: The PREVEND Study (Riphage et al.)

Matrix Gla Protein (MGP) is a strong vitamin K-dependent inhibitor of soft tissue calcification. Researchers 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 in a study recently published in Nutrients.

The prospective general population-based Prevention of Renal and Vascular End-Stage Disease (PREVEND) study included 4275 subjects (aged 53 ± 12 years, 46.0% male). 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. The researchers 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.

The researchers concluded that this study provides insights into the prevalence of functional vitamin K insufficiency and its clinical implications in a large general population-based cohort. It was demonstrated that functional vitamin K insufficiency is common in the general population and occurs even more frequently among the elderly and subjects with hypertension, type 2 diabetes, CKD, and CVD.

Furthermore, the researchers wrote that they “found that plasma dp-ucMGP was curvilinearly associated with an increased risk for all-cause and cardiovascular mortality. Importantly, a low vitamin K status is not only a clinically relevant risk factor for adverse health outcomes, but may also be a modifiable risk factor. Given the availability of vitamin K supplements, vitamin K insufficiency seems an attractive target for preventive intervention. Future prospective clinical trials are needed to investigate whether the correction of low vitamin K status can indeed improve health outcomes.”


Riphagen J et al. Prevalence and Effects of Functional Vitamin K Insufficiency: The PREVEND Study. Nutrients 2017, 9, 1334; doi:10.3390/nu9121334.




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