Abstract 19353: Decrease in Matrix Gla Protein Level is Associated with Faster Progression of Aortic Valve Stenosis in a Substudy of ASTRONOMER: Relationship with Age
Background: Matrix Gla protein (MGP) is an inhibitor of cardiovascular calcification. The objective of this substudy was to examine, in a large prospective multicenter study, the relationship between change in MGP levels and progression of aortic stenosis (AS).
Methods and results: In ASTRONOMER study, 257 patients had an echocardiographic follow-up (mean follow-up: 3.4 ±1.2 yrs) and progression of AS was assessed by the measurement of the annualized increase in mean gradient. Serum levels of MGP were measured by ELISA method at baseline and at last follow-up and annualized change was calculated. Progression rate of gradient was directly related to baseline degree of valve calcification evaluated by echocardiography (r=0.28, p<0.0001) and inversely related to the change in MGP level during follow-up (r=−0.29, p<0.0001). Clinical diagnosis of metabolic syndrome (MetS) was also associated (p=0.03) with faster progression of mean gradient. In a linear multivariate model adjusted for age, smoking history, valve morphology, status of randomization (statin vs. placebo) and MetS, a higher degree of valve calcification (β = 0.88, p=0.04), male gender (β=0.61, p=0.04) and a decrease in MGP serum level (β=−0.52, p=0.01) were independent predictors of faster progression of gradient (R2= 0.3, p<0.0001). The significant association between reduction in MGP and gradient progression rate was observed only in the elderly patients (≥70 years old) and not in the younger patients. In a multivariate model adjusted for age, gender, smoking history, status of randomization, MetS, and baseline valvular calcification, a reduction in MGP level (β=−1.44, p=0.004) was a powerful independent predictor of faster progression of mean gradient (R2= 0.44, p=0.03) in patients ≥70 years old.
Conclusion: This is the first prospective study to demonstrate an inverse relationship between change in circulating MGP level and progression rate of AS. Future studies are needed to determine if a reduction in MGP over time is a surrogate marker of disease progression or a factor contributing to disease process. These findings also suggest that the determinants and mechanisms of stenosis progression may be different in old versus young patients.
- © 2010 by American Heart Association, Inc.