Abstract 17551: Association between Circulating Matrix Gla Protein and Progression of Aortic Stenosis: A Substudy of the ASTRONOMER Trial

Abstract

Background: In a previous substudy of the ASTRONOMER trial, we reported that metabolic syndrome (MetS) is associated with faster progression of aortic stenosis (AS). Recent studies suggested that dysregulation of mineral metabolism could play a role in the pathogenesis of AS. The carboxylated form of the Matrix Gla Protein (MGP) is an inhibitor of ectopic calcification. The aim of this study was to determine the association between levels of the total (i.e. carboxylated and non carboxylated) MGP and AS progression rate.

Methods: Among the 269 patients randomized in ASTRONOMER, mean follow-up time 3.4 ±1.3yrs, 217 had measurement of circulating level of total MGP. None of them had hypercholesterolemia, diabetes or CAD. However, 29% had hypertension and 28% MetS. AS progression rate was measured with the annualized increase in peak aortic jet velocity (V_peak).

Results: In the whole cohort, MGP level was associated with AS progression rate in univariate analysis (r=0.15; p=0.03) but not in multivariate analysis. There was an interaction (p=0.03) between MGP level and age with respect to its relationship with AS progression rate. In patients with age<57yrs (median value), higher MGP level was significantly associated with faster AS progression rate (r=0.22; p=0.02) but not in older patients. After adjustment for gender, hypertension, LDL-chol, creatinine, degree of AV calcification, V_peak, and status of randomization, higher MGP level (p=0.008) and MetS (p=0.001) were independent predictors of faster AS progression in younger patients. MGP level was positively related to age (p=0.03), LDL-chol (p=0.02), oxidized-LDL (p=0.005), glycaemia (p=0.001), and HOMA index (p=0.05). In multivariate analysis, oxidized-LDL (p=0.03) and glycaemia (p=0.01) were the only two factors independently associated with MGP level.

Conclusion: This study reports an association between total circulating MGP levels and faster AS progression in younger patients. These findings suggest that valvular calcification may lead to increased MGP expression, perhaps in a feedback attempt to physiologically reduce bone-like formation of calcium deposits in the valve. Further studies with measures of both forms of MGP are needed to clarify the exact role of the MGP system in AS.