Abstract 11959: The Relationship of Matrix Gla Protein With Coronary and Extracoronary Calcification in the Multi-Ethnic Study of Atherosclerosis

Abstract

Introduction: Vascular calcification regulators are understudied. Matrix Gla protein (MGP) is a calcification inhibitor, and its inactive dephosphorylated-uncarboxylated (dp-ucMGP) form has been linked to calcification. The longitudinal relationship of dp-ucMGP with coronary and extracoronary artery calcification in large populations is unknown. Hypothesis: Higher levels of dp-ucMGP may be associated with greater coronary artery, ascending thoracic aortic, and descending thoracic aortic calcification (CAC, ATAC, DTAC). Aim: To determine the association of dp-ucMGP with CAC, ATAC, and DTAC. Methods: Calcification was measured on serial thoracic computed tomography (CT) scans in the Multi-Ethnic Study of Atherosclerosis (MESA, n=6814). Dp-ucMGP was measured at baseline in a random subset of available serum samples (n=2663), 2539 included in the fully adjusted models) in participants with a baseline (2000-02) and follow-up CTs at Exam 5 (2010-12) ( InaKtif MGP ELISA, Perkin Elmer, Waltham, MA). Linear mixed effect models were used to determine the association of baseline dp-uc MGP levels with long-term CAC, ATAC, and DTAC incidence and progression. Results: Participants were on average 61 + 9 years, 51.3% women, and 37.7% white. For each one standard deviation (178 pmol/L) increase in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p<0.001) Agatston units/year (AU/year), ATAC increased by 0.63 ([95% CI = 0.27, 0.98], p=0.001) AU/year, and DTAC increased by 8.61 ([95% CI = 4.55, 12.67], p<0.001) AU/year, in fully adjusted models. Conclusion: We found an association of the inactive form of matrix Gla protein, dp-ucMGP, with long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate MGP as a calcification regulator and possible therapeutic target.