title: Impact of menaquinone-4 supplementation on coronary artery calcification and arterial stiffness: an open label single arm study.
abstract: Dietary intake of vitamin K has been reported to reduce coronary artery calcification (CAC) and cardiovascular events. However, it is unknown whether supplemental menaquinone (MK)-4 can reduce CAC or arterial stiffness. To study the effect of MK-4 supplementation on CAC and brachial ankle pulse wave velocity (baPWV).
  
  
  
  This study is a single arm design to take 45 mg/day MK-4 daily as a therapeutic drug for 1 year. Primary endpoint was CAC score determined using 64-slice multislice CT (Siemens), and the secondary endpoint was baPWV measured before and 1 year after MK-4 therapy.
  
  
  
  A total of 26 patients were enrolled. The average age was 69 ± 8 years and 65 % were female. Plasma levels of phylloquinone (PK), MK-7, and MK4 were 1.94 ± 1.38 ng/ml, 14.2 ± 11.9 ng/ml and 0.4 ± 2.0 ng/ml, respectively, suggesting that MK-7 was the dominant vitamin K in the studied population. Baseline CAC and baPWV were 513 ± 773 and 1834 ± 289 cm/s, respectively. At 1 year following MK-4 supplementation, the values were 588 ± 872 (+14 %) and 1821 ± 378 cm/s (-0.7 %), respectively. In patients with high PIVKA-2, -18 % annual reduction of baPWV was observed.
  
  
  
  Despite high dose MK-4 supplementation, CAC increased +14 % annually, but baPWV did not change (-0.7 %). The benefits of MK-4 supplementation were only observed in patients with vitamin K insufficiencies correlated with high PIVKA-2 baseline levels, reducing baPWV but not CAC.
  
  
  
  This study was registered as UMIN 000002760.
authors.affiliation: Department of Cardiovascular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan. ikari@is.icc.u-tokai.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikari
authors.affiliation: Department of Cardiovascular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Torii
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, 1-5-7 Asahimachi, Abenoku, Osaka, 545-0051, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shioi
authors.affiliation: Department of Hygienic Sciences, Kobe Pharmaceutical University, 4-9-1 Motoyamakitamachi, Higashinadaku, Kobe, 658-0003, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Okano
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D015992:Body Mass Index; D009202:Cardiomyopathies / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D019587:Dietary Supplements; D023381:Endpoint Determination; D005260:Female; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D012307:Risk Factors; D059289:Vascular Stiffness / Q000187:drug effects*; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000097:blood; D024482:Vitamin K 2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D006490:Hemostatics; D024482:Vitamin K 2; C030814:menatetrenone; D010837:Vitamin K 1; C062629:menaquinone 7
keywords: Coronary artery calcification; Pulse wave velocity; Vitamin K