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Background and Aims: A high dietary intake of vitamin K1 (phylloquinone) and vitamin K2 (menaquinones) is thought to decrease cardiovascular disease risk by reducing vascular calcification. The objective of this study is to explore if there is a relationship between phylloquinone and menaquinones intake and risk of PAD., Methods: We investigated the association between intake of phylloquinone and menaquinones with PAD in a prospective cohort with 36,629 participants. Occurrence of PAD was obtained by linkage to national registries. Baseline intake of phylloquinone and menaquinones was estimated using a validated food-frequency questionnaire. Multivariate Cox regression was used to estimate adjusted hazard ratio's for the association., Results: During 12.1 years (standard deviation 2.1 years) of follow-up, 489 incident cases of PAD were documented. Menaquinones intake was associated with a reduced risk of PAD with a hazard ratio (HR) of 0.71, 95% CI; 0.53-0.95 for the highest versus lowest quartile. A stronger association was observed (p interaction 0.0001) in participants with hypertension (HRQ4 versus Q1 0.59; 95% CI 0.39-0.87) or diabetes (HRQ4 versus Q1 0.56; 95% CI 0.18-1.91), though confidence intervals were wide in the small (n = 530) diabetes stratum. Phylloquinone intake was not associated with PAD risk., Conclusions: High intake of menaquinones was associated with a reduced risk of PAD, at least in hypertensive participants. High intake of phylloquinone was not associated with a reduced risk of PAD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Context: The Metabolic Syndrome (MetS) is a cluster of metabolic abnormalities and is associated with increased risk of diabetes and cardiovascular diseases. Phylloquinone, menaquinones, and vitamin K status are associated with several components of MetS, but the association with MetS has hardly been studied to date., Objective: This study aimed to examine whether the intake and/or status of vitamin K is associated with MetS and its components., Design: This study comprised two cohorts, one of 402 women and one of 400 men (age 40-80 y). At followup 625 participants were still alive and willing to participate. Data were analyzed both cross sectionally and longitudinally with Poisson and linear regression adjusted for multiple confounders. Baseline phylloquinone/menaquinone intakes were measured with a validated food frequency questionnaire and vitamin K status with serum desphospho-uncarborxylated matrix-Gla protein level., Results: At baseline 270 (34.5%) participants had MetS and 171 (35.7%) at followup. Cross sectionally, high menaquinones intakes were associated (P(trend) = .08) with a lower prevalence of MetS with a prevalence ratio (PR) of 0.74 (95% confidence interval [CI], 0.54-1.03) for the highest vs the lowest tertile. At followup, the highest tertiles of menaquinones intake (PR = 0.62; 95% CI, 0.40-0.95) and vitamin K status (PR = 0.57; 95% CI, 0.38-0.87) were associated (P(trend) = .01) with a lower occurrence of MetS. These associations were mainly driven by relations with lower triacylglycerol concentrations for menaquinones and lower waist circumference for vitamin K status. Phylloquinone intake was not associated with MetS prevalence., Conclusions: This study shows that a high intake of menaquinones and high vitamin K status are associated with a lower occurrence of MetS.

Matrix Gla protein (MGP) is a vitamin K-dependent protein and an inhibitor of vascular calcification. Vitamin K is required for the carboxylation of MGP and can thereby reduce calcification. Circulating MGP species with different conformations have been investigated as markers for coronary artery calcification (CAC). In high-risk populations, high total uncarboxylated MGP (t-ucMGP) was associated with decreased CAC, while high non-phosphorylated uncarboxylated MGP (dp-ucMGP) was associated with a poor vitamin K status. This cross-sectional study investigated the association of MGP species with CAC, vitamin K status among 200 healthy women. Circulating dp-ucMGP, t-ucMGP and, non-phosphorylated carboxylated MGP (dp-cMGP) levels were measured by ELISA techniques and Agatston score by multi-detector computed tomography. The ratio of uncarboxylated to carboxylated osteocalcin was used as proxy of vitamin K status. A borderline significant (P=.06) association between higher circulating dp-ucMGP levels and high CAC was observed (β=0.091, 95% CI-0.01; 0.19). In the entire study population, high t-ucMGP levels tended to be associated (P=.09) with lower CAC (β=-0.36, 95% CI:-0.78; 0.06). This association strengthened amongst women with CAC to a significant relation between high t-ucMGP levels and lower CAC (β=-0.55, 95% CI-1.01;-0.10). Dp-cMGP was not associated with CAC. Low vitamin K-status was associated with high dp-ucMGP concentrations (β=0.138, 95% CI 0.09; 0.19) but not with other MGP species. These results show that dp-ucMGP may serve as a biomarker of vitamin K status. Circulating dp-ucMGP and t-ucMGP may serve as markers for the extent of CAC, but these findings need to be confirmed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

OBJECTIVE-To investigate the relationship of circulating matrix Gla protein (MGP) species with incident cardiovascular disease (CVD) or coronary heart disease (CHD) in type 2 diabetic patients. RESEARCH DESIGN ANDMETHODS-EPIC-NL is a prospective cohort study among 40,011 Dutch men and women. At baseline (1993-1997), 518 participants were known to have type 2 diabetes. MGP levels weremeasured by ELISA techniques in baseline plasma samples. The incidence of fatal and nonfatal CVD and CVD subtypesdCHD, peripheral arterial disease (PAD), heart failure, and strokedwere obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs), adjusted for sex, waist-to-hip ratio, physical activity, and history of CVD. RESULTS-During a median 11.2 years of follow-up, 160 cases of CVD were documented. Higher circulating desphospho-uncarboxylated MGP (dp-ucMGP) levels were significantly associated with higher risk of CVD, with an HR per SD (HRSD) of 1.21 (95%CI 1.06-1.38), PAD (HRSD 1.32 [95% CI 1.07-1.65]), and heart failure (HRSD 1.75 [95% CI 1.42-2.17]) after adjustment. Higher circulating dp-ucMGP levels were not related to risk of CHD (HRSD 1.12 [95% CI 0.94-1.34]) or stroke (HRSD 1.05 [95% CI 0.73-1.49]). Circulating desphosphocarboxylated MGP and circulating total-uncarboxylated MGP levels were not associated with CVD or CVD subtypes. CONCLUSIONS-High dp-ucMGP levels were associated with increased CVD risk among type 2 diabetic patients, especially with the subtypes PAD and heart failure, while other MGP species were not related to CVD risk. These results suggest that a poor vitamin K status is associated with increased CVD risk. [ABSTRACT FROM AUTHOR]