Impact of menaquinone-4 supplementation on coronary artery calcification and arterial stiffness: an open label single arm study

摘要

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.