Abstract P397: Circulating Species of Matrix Gla Protein and the Risk of Vascular Calcification in Healthy Women

Background: Matrix Gla protein (MGP) is an inhibitor of vascular calcification that requires vitamin K for its carboxylation. Circulating MGP occurs as various species with different conformations depending on carboxylation and phosphorylation. Total uncarboxylated MGP (t-ucMGP) is the sum of non-phosphorylated and phosphorylated uncarboxylated MGP (dp-ucMGP and p[[Unable to Display Character: ‑]]ucMGP) and mainly consists of p-ucMGP. Due to its phosphorylated group p-ucMGP has a strong calcium-binding capacity irrespective of the Gla content. In high risk populations, high levels of t[[Unable to Display Character: ‑]]ucMGP were associated with decreased calcification, while high levels dp-ucMGP were associated with low vitamin K status and increased vascular calcification. These relations have never been investigated in a healthy population. Objective: This prospective study investigates the association between circulating matrix Gla protein species and vascular calcifications among postmenopausal women. Design: In a prospective cohort of 571 healthy women, MGP levels were measured by ELISA techniques at baseline. Vitamin K intake was estimated from a validated food frequency questionnaire. Calcification was measured in the coronary arteries, aortic valve, mitral valve, and aortic arch by multi-detector computed tomography after 8.5 years follow-up. Coronary artery calcification (CAC) was defined present if Agatston score was ≥10 and the calcification score was calculated as the sum of the calcified areas. Multivariate adjusted relative risks (RR) and odds ratios (OR) were estimated using modified Poisson regression and multinomial logistic regression per standard deviation of MGP species and the no calcification group was used as reference. Results: Of the women, 24% had no calcification while 5% had calcification in all areas. High dp-ucMGP levels, reflecting poor vitamin K status, were (p=0.08) associated with more CAC (RR SD 1.07;95%CI 0.99-1.15) and calcification areas (OR (4 areas vs no calcification) 1.49; 95%CI 0.95-2.35, p=0.09). High t-ucMGP levels were associated with less calcification (OR (4 areas vs no calcification) 0.63; 95%CI 0.36-1.10, p=0.10). Desphospho-carboxylated MGP was not associated with calcification. High phylloquinone intake was not associated with the number of calcified areas OR (4 areas vs no calcification) 1.14 (95%CI: 0.72-1.81, p=0.57). In contrast, higher menaquinones intake was associated with less calcification areas (OR (4 areas vs no calcification) 0.39; 95%CI: 0.21-0.74, p=0.004). Conclusion: High dp-ucMGP levels, reflecting a poor vitamin K status, may be associated with more calcification, also in a healthy population. High menaquinones intake was associated with less calcification. Consistent with high-risk populations, high t-ucMGP levels seem to associated with fewer calcification areas.