Abstract 594: Matrix Gla Protein Associates With Coronary Artery Calcification and Increases in Subacute Myocardial Infarction Together With Inflammatory Activation by Tumor Growth Factor-β1

Abstract

Osteogenic Proteins (OP) and atherosclerotic inflammation modulate vascular calcification. Patients with acute myocardial infarction (MI) demonstrate higher inflammation and develop accelerated coronary artery calcification (CAC), compared to stable coronary artery disease patients. We aimed to: (a) test the association of OP and inflammatory proteins with CAC in individuals assessed for primary cardiovascular prevention; (b) evaluate these biomarkers in acute and subacute phases post-MI. We prospectively enrolled 170 patients, divided in 3 groups: (1) primary prevention patients who underwent ambulatory coronary computed tomography with a CAC score ≥ 100, n=100; (2) primary prevention patients with a CAC score=zero, n=30; (3) post-MI patients, n=40, during acute (3±1 days post-MI) and subacute (46±17 days post-MI) phases. Serum OP (osteoprotegerin, RANKL, fetuin-A and Matrix Gla protein [MGP]) and serum inflammatory proteins (C-reactive protein, oxidized LDL, tumoral necrosis factor-α and tumor growth factor [TGF]-β1) were measured by ELISA. Associations of plasma OP and inflammatory proteins levels with CAC were adjusted by age, sex and use of statins. In the post-MI group, all biomarkers were compared both in acute vs. subacute phases and in acute phase vs. CAC zero group. Compared to CAC zero, patients with CAC score ≥ 100 were older, predominantly men and had higher rates of hypertension and diabetes. After adjusted analysis, only MGP was associated with a CAC score ≥ 100 (OR 1.48 [95% CI 1.01-2.16; per 100ng/ml increase; p=0.047). Serum MGP and TGF-β1 were higher in subacute phase compared to acute phase post-MI (median [25-75 percentile], 342 vs. 279ng/ml respectively; p=0.01 and 711 vs. 492pg/ml; p=0.03). All biomarkers were similar in acute phase post-MI vs. CAC zero. In conclusion, serum MGP was associated with higher CAC in primary cardiovascular prevention patients. After MI, both serum MGP and TGF-β1 levels increased in the subacute phase. Our findings unveiled a potential role for MGP as a biomarker of CAC in primary cardiovascular prevention. Additionally, this clinical study unfolds further mechanistic hypothesis of how increased TGF-β1 and MGP may modulate vascular inflammation and CAC progression in subacute MI patients.