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J Nutr Sci. 2016 Dec 29;5:e48. doi: 10.1017/jns.2016.20. eCollection 2016.

Plasma phylloquinone, menaquinone-4 and menaquinone-7 levels and coronary artery calcification.

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Department of Cardiovascular Medicine, Tokai University School of Medicine, Isehara, Japan.
Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan.
Division of Nephrology, Endocrinology, and Metabolism, Tokai University School of Medicine, Isehara, Japan.
Department of Cardiology, Ibaraki Seinan Medical Center Hospital, Ibaraki, Japan.
Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan.


Vitamin K is considered to be involved in the pathological mechanisms of coronary artery calcification (CAC). Correlation between CAC and plasma vitamin K levels was studied. A total of 103 patients, with at least one coronary risk factor, were studied. CAC was measured using 64-slice multislice computed tomography (MSCT) and divided into three groups: none (CAC score = 0; n 25), mild to moderate (0 < CAC score < 400; n 52) and severe (CAC score > 400; n 26). Phylloquinone (PK) and menaquinone (MK)-4 and MK-7 were measured by HPLC-tandem MS. Mean age of patients was 64 (sd 13) years, of which 57 % were male. Median CAC score was 57·2. Median levels of PK, MK-4 and MK-7 were 1·33, 0 and 6·99 ng/ml, showing that MK-7 was the dominant vitamin K in this population. MK-7 showed a significant inverse correlation with uncarboxylated osteocalcin (ucOC, P = 0·014), protein induced by vitamin K absence of antagonist-2 (PIVKA-2, P = 0·013), intact parathyroid hormone (P = 0·007) and bone-specific alkaline phosphatase (P = 0·018). CAC showed an inverse correlation with total circulating uncarboxylated matrix Gla protein (t-ucMGP, P = 0·018) and Hb (P = 0·05), and a positive correlation with age (P < 0·001), creatinine, collagen type 1 cross-linked N-terminal telopeptide (NTX, P = 0·03), pulse wave velocity (P < 0·001) and osteoprotegerin (P < 0·001). However, CAC did not have a significant correlation with plasma levels of PK, MK-4 or MK-7. In conclusion, plasma MK-7, MK-4 or PK level did not show significant correlation with CAC despite the association between plasma vitamin K levels and vitamin K-dependent proteins such as ucOC or PIVKA-2.


BAP, bone-specific alkaline phosphatase; CAC, coronary artery calcification; Coronary artery calcification; MGP, matrix Gla protein; MK, menaquinone; Matrix Gla protein; NTX, N-terminal telopeptide; OC, osteocalcin; OPG, osteoprotegerin; Osteocalcin; PIVKA-2, protein induced by vitamin K absence of antagonist-2; PK, phylloquinone; PTH, parathyroid hormone; PWV, pulse wave velocity; Vitamin K; t-ucMGP, total circulating uncarboxylated matrix Gla protein; ucOC, uncarboxylated osteocalcin

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