Is Matrix Gla Protein Associated with Vascular Calcification? A Systematic Review

Systematic review of observational studies and randomized trials examining circulating matrix Gla protein fractions and vascular calcification. Included populations were people with atherosclerosis, chronic kidney disease including dialysis and end-stage kidney disease, diabetes, healthy controls, and participants receiving vitamin K supplementation or vitamin K antagonists, with calcification assessed in coronary, aortic, carotid, peripheral, and valvular beds.

Included interventional studies evaluated vitamin K regimens across several populations: MK-7 360 µg once daily in hemodialysis patients; MK-7 90 µg plus cholecalciferol 10 µg in non-dialyzed CKD stages 3-5; MK-4 15 mg three times daily plus cholecalciferol 10 µg in cardiovascular disease; and phylloquinone 500 µg once daily in postmenopausal women. Across the review, vitamin K supplementation was assessed mainly for effects on non-functional MGP fractions and vascular calcification outcomes.

Overall, vitamin K supplementation reduced dp-ucMGP but did not reliably slow vascular calcification progression. In the included intervention studies, dp-ucMGP rose with increasing aortic calcification severity in hemodialysis patients, but the baseline calcification score did not correlate with the subsequent dp-ucMGP drop. In CKD stages 3-5, there was no difference in coronary CAC progression between MK-7 plus cholecalciferol and comparator treatment, and CAC still increased despite MK-4 treatment; in postmenopausal women, neither baseline nor change in MGP concentrations predicted CAC change. The review concluded that no single MGP fraction consistently predicted calcification across settings and that the evidence was too heterogeneous to support a universal biomarker role.

The evidence was highly heterogeneous in calcification territory, MGP fraction measured, populations, and study design. Several included studies were small, and the review notes limitations in study quality and inconsistency across outcomes, which weaken causal interpretation. Findings are also indirect across different disease states and vitamin K formulations, and calcification outcomes were not uniformly improved even when biochemical markers changed.