Matrix Gla protein and the long-term incidence and progression of coronary artery and aortic calcification in the Multi-Ethnic Study of Atherosclerosis

Authors: BERLOT, ASHLEY - Albert Einstein College Of Medicine; FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; TRACY, RUSSELL - University Of Vermont; BUDOFF, MATTHEW - Ucla Medical Center; KIM, RYUNG - Albert Einstein College Of Medicine; NAVEED, MAHIM - San Francisco Veteran Affairs Medical Center; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; KIZER, JORGE - University Of California San Francisco (UCSF); BORTNICK, ANNA - Albert Einstein College Of Medicine

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/5/2024
Publication Date: 5/1/2024
Citation: Berlot, A.A., Fu, X., Shea, K., Tracy, R., Budoff, M., Kim, R.S., Naveed, M., Booth, S.L., Kizer, J.R., Bortnick, A.E. 2024. Matrix Gla protein and the long-term incidence and progression of coronary artery and aortic calcification in the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. https://doi.org/10.1016/j.atherosclerosis.2024.117505.
DOI: https://doi.org/10.1016/j.atherosclerosis.2024.117505

Interpretive Summary: Coronary artery calcification is an indicator of heart disease. Low amounts of vitamin K have been implicated in an increased risk of coronary artery calcification in older adults; however, this has not been studied in a diverse population with an extended follow-up. To address this gap, a vitamin K biomarker was measured in 2663 older adults participating in the Multi-Ethnic Study of Atherosclerosis who were followed for 10 years. Higher vitamin K status was associated with less progression of coronary artery calcification. These data provide justification for future clinical studies focused on vitamin K intake and heart disease risk.

Technical Abstract: Background and aims: Matrix Gla protein (MGP) is an inhibitor of calcification that requires carboxylation by vitamin K for activity. The inactive form of MGP, dephosphorylated-uncarboxylated matrix Gla protein (dpucMGP), has been associated with increased calcification. However, it is not known whether there is a longitudinal relationship between dephosphorylated-uncarboxylated matrix Gla protein levels and coronary and aortic calcification in large population cohorts. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) followed participants with serial cardiac computed tomography (CT) measures of vascular calcification. Dp-ucMGP was measured at baseline in a subset of participants who completed baseline and follow-up CTs approximately 10 years later and had available plasma specimens (n = 2663). Linear mixed effects models (LMMs) were used to determine the association of dp-ucMGP with the simultaneous incidence and progression of coronary artery, ascending thoracic aortic, or descending thoracic aortic calcification (CAC, ATAC, DTAC)]. Results: For every one standard deviation (SD, 178 pmol/L) increment 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. The association was stronger for DTAC in those 65 years and older, and with diabetes. Conclusions: We found a positive association of the inactive form of matrix Gla protein, dp-ucMGP, and long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate dp-ucMGP as a calcification regulator and MGP as a possible therapeutic target to slow progression of calcification in the vasculature.