Inactive Matrix Gla Protein and Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis

BACKGROUND: MGP (matrix Gla protein) inhibits arterial calcification. Higher inactive MGP, in its dephosphorylated-uncarboxylated (dp-uc) form, is positively associated with vascular calcification, possibly portending adverse cardiovascular events. The objective of this study was to determine the association of dp-ucMGP with incident cardiovascular disease (CVD) events and mortality in MESA (Multi-Ethnic Study of Atherosclerosis). METHODS: MESA is a prospective cohort study of 45-to 84-year-old individuals enrolled between 2000 and 2002 with adjudicated outcomes through 2019. Dp-ucMGP was measured at baseline in n=2663 participants with cardiac computed tomography at Exams 1 (2000-2002) and 5 (2010-2012). Age-stratified Cox proportional hazard models were used to assess dp-ucMGP with risk of all CVD (mean follow-up 16±4 years), hard CVD (17±3 years), hard coronary heart disease (17±3 years), and all-cause mortality (18±2 years). RESULTS: The youngest age quartile (45-to 53-years-old) with higher dp-ucMGP levels (520-2934 pmol/L) had an increased risk of all CVD (hazard ratio [HR], 3.05 [95% CI, 1.58-5.90], P=0.001), hard CVD (HR, 2.85 [95% CI, 1.30-6.23], P=0.009), hard coronary heart disease (HR, 3.79 [95% CI, 1.31-10.95], P=0.014), and all-cause mortality (HR, 2.73 [95% CI, 1.19-6.30], P=0.018) compared with those with dp-ucMGP levels between 150 and 519 pmol/L in maximally adjusted models. CONCLUSIONS: Younger individuals 45 to 53 years old with elevated dp-ucMGP levels (≥520 pmol/L) had an increased risk of incident CVD, coronary heart disease, and all-cause mortality. No association was seen in older adults. Additional studies are needed to better delineate the relationship of inactive MGP with incident CVD, coronary heart disease, and all-cause mortality.