Abstract 4127990: Inactive Matrix Gla Protein and Cardiovascular Outcomes: the Multi-Ethnic Study of Atherosclerosis

Background: Matrix Gla protein (MGP) inhibits arterial calcification. Higher inactive MGP, dephosphorylated-uncarboxylated (dp-ucMGP), is positively associated with vascular calcification, possibly portending cardiovascular events. The objective was to determine the association of dp-ucMGP with incident cardiovascular disease (CVD) events and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: MESA is a cohort study of 45-84 year-old individuals enrolled between 2000-02 with adjudicated outcomes through 2019. Dp-ucMGP was measured at baseline in n=2663 participants with cardiac computed tomography at Exams 1 (2000-02) and 5 (2010-12). Using age-stratified Cox proportional hazard models, adjusted for sex, race-ethnicity, body mass index, systolic blood pressure, statin use, anti-hypertensive medication use, smoking status, physical activity, alcohol use, diabetes, high density lipoprotein, low density lipoprotein, triglycerides, phosphate, and estimated glomerular filtration rate, we determined the association of dp-ucMGP with risk of all CVD (mean follow-up 16 + 4 years), hard CVD (17 + 3 years), hard CHD (17 + 3 years), and all-cause mortality (18 + 2 years). Results: The youngest age quartile (45-53-years-old) with higher dp-ucMGP levels (520-2934 pmol/L) had an increased risk of all CVD (HR 3.01 [95% CI 1.56, 5.80], p=0.001), hard CVD (HR 2.78 [95% CI 1.29, 6.02], p=0.009), hard CHD (HR 3.37 [95% CI 1.29, 8.81], p=0.013) and all-cause mortality (HR 2.69 [95% CI 1.06, 6.79], p=0.037) compared to dp-ucMGP levels between 150-519 pmol/L in maximally adjusted models. There was no relationship with any outcomes for the other age quartiles (Table). Conclusions: Middle aged individuals with elevated dp-ucMGP levels ( > 520 pmol/L) had an increased risk of incident CVD, CHD, and all-cause mortality.