5.4 MATRIX GLA PROTEIN IN RELATION TO LEFT VENTRICULAR DIASTOLIC FUNCTION

Abstract

Introduction: Matrix Gla Protein (MGP) is highly expressed in cardiomyocytes and is upregulated after acute and chronic pressure overload and in myocardial hypertrophy in mice and humans. However, no study addressed the relation between cardiac function and MGP in humans. Methods and results: In 767 participants randomly recruited from the Flemish population (51.5% women, mean age 50.6 years), we measured circulating levels of nonphosphorylated and uncarboxylated MGP (dp-ucMGP) and recorded early and late diastolic peak velocities of mitral inflow (E and A) by conventional Doppler and the mitral annular velocities (e′ and a′) by tissue Doppler imaging. Using principal component analysis, we summarized 7 Doppler indexes - namely, E, A, e′ and a′ velocities, and their ratios (E/A, e′/a′, and E/e′) - into a single diastolic score. According to published definitions, 73 (9.5%) participants had impaired relaxation and 114 (14.9%) had elevated LV filling pressure. In the continuous analysis, a doubling of dp-ucMGP is associated with a 6.9% increase in the diastolic score (95% CI 2.7–10.6, P < 0.001). No association was seen between systolic function and dp_ucMGP. Multivariable-adjusted odds ratio for a doubling of dp-ucMGP was 0.70 (95% CI 0.50–0.98; P = 0.038) for having elevated LV filling pressure. No significant association was seen between impaired relaxation and dp-ucMGP. Conclusion: Higher circulating levels of dp-ucMGP are associated with better LV diastolic function. Pending confirmation in other cohorts and further experimental studies are required to translate our epidemiological findings into underlying molecular mechanisms.