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

ABSTRACT: 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.

SUBMITTER: Riphagen IJ

PROVIDER: S-EPMC5748784 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Riphagen Ineke J IJ Keyzer Charlotte A CA Drummen Nadja E A NEA de Borst Martin H MH Beulens Joline W J JWJ Gansevoort Ron T RT Geleijnse Johanna M JM Muskiet Frits A J FAJ Navis Gerjan G Visser Sipke T ST Vermeer Cees C Kema Ido P IP Bakker Stephan J L SJL

Nutrients 20171208 12

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 o ...[more]

PMID: 29292751

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Project description:Background and purposeVitamin D insufficiency may be common among elite athletes, but prevalence is unclear, and some potentially important risk factors are uncertain. The present study aimed to (a) estimate the prevalence of vitamin D insufficiency in elite athletes, and (b) examine differences in prevalence between the sexes, and between adults and adolescents, from recent studies which used a contemporary definition of insufficiency.MethodsFour databases (Web of Science, SPORTDiscus, PubMed, and Sports Medicine and Education Index) were searched for studies in elite athletes. Literature selection, data extraction, and risk of bias assessment were conducted independently by two researchers. Vitamin D insufficiency was defined as 25(OH)D < 50 nmol/L. Meta-analysis was conducted, using R software x64 4.0.2, to provide estimates of prevalence of insufficiency for adults and adolescents, and to examine between-sex differences in risk of insufficiency.ResultsFrom the initial 943 literature search hits, 51 studies were eligible with 5456 participants, 33 studies in adults (12/33 in winter and spring), 15 studies in adolescents (6/15 in winter and spring) and 3 studies with age of study participants not given. Prevalence of vitamin D insufficiency from meta-analysis was 30% (95% CI 22-39%) in adults and prevalence was higher, though not significantly so, at 39% (95% CI 25-55%) in adolescents. Differences in the prevalence of insufficiency between the sexes for the eight studies which provided within-study comparisons was not significant (RR = 1.0; 95% CI 0.79-1.26). Evidence quality was moderate.ConclusionsPrevalence of vitamin D insufficiency (≤ 50 nmol/L) in elite athletes is high, suggesting a need for greater attention to prevention and treatment. Prevalence estimates in the present study are conservative due to a relative lack of studies in winter. While there was no evidence of higher risk among women than men in the present study, there was less evidence on women.

Project description:BackgroundVitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency.MethodsWe undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants.FindingsVariants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile.InterpretationVariants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency.FundingFull funding sources listed at end of paper (see Acknowledgments).

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

Publications

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

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