Abstract 15006: Circulating Inactive Matrix Gla-Protein is Associated With High Aldosterone Levels and Arterial Stiffness in Hypertension
Background: large artery stiffness leads to systolic hypertension and increases pulsatile arterial load to the left ventricle. Large artery stiffening is partially dependent on vascular calcification. Matrix Gla-protein is a vitamin K-dependent protein that strongly inhibits arterial calcification. Vitamin K deficiency leads to production of inactive non-phosphorylated and uncarboxylated matrix Gla protein (dp-ucMGP). We assessed the relationship between levels of desphospho-uncarboxylated MGP (dp-ucMGP, indicating impaired MGP activation) and arterial stiffness in hypertension.
Methods: We studied 176 subjects with hypertension. dp-ucMGP MGP was measured with a proprietary ELISA assay (VitaK; The Netherlands). In a subgroup of subjects (n=105) we measured carotid-femoral pulse wave velocity (PWV), a measure of large artery stiffness, using arterial tonometry (Sphygmocor Device). dp-ucMGP was measured with a proprietary ELISA assay (VitaK; The Netherlands). Plasma aldosterone was measured by ELISA (Cayman Chemicals ; USA).
Results: dp-ucMGP was significantly associated with plasma aldosterone (R=0.42; P<0.0001). This association was independent of age, gender, ethnicity, ACE inhibitor, angiotensin receptor blocker or spironolactone use (standardized beta=0.41; P<0.00001). Other significant correlates of dp-ucMGP included older age (Standardized Beta=0.22; P=0.04) and warfarin use (Standardized Beta=0.33; P=0.003). dp-ucMGP predicted carotid-femoral pulse wave velocity (Beta=0.37; P<0.0001), even after adjustment for age, gender, mean arterial pressure and heart rate (Beta=0.22; P=0.01).
Conclusions: Inactive MGP is associated with large artery stiffness in hypertension. Our study also demonstrates a novel independent association between high aldosterone levels and dp-ucMGP, suggesting that aldosterone may influence the MGP pathway, which may be involved in its effect on vascular calcification. Whether targeting MGP activation with vitamin K supplementation and/or aldosterone antagonists remains to be tested in future trials.
Author Disclosures: J.A. Chirinos: Research Grant; Significant; NIH, American College of Radiology Network, Fukuda Denshi, Bristol Myers Squibb, Microsoft and CVRx Inc. Other Research Support; Modest; Fukuda Denshi, Withings, Atcor Medical. Consultant/Advisory Board; Modest; Fukuda Denshi, Microsoft Research, Merck and Vital Labs. Consultant/Advisory Board; Significant; Bristol Myers Squibb, OPKO Healthcare. I. Vassim: None. S. Varakantam: None. T.S. Phan: None. A. Syed: None. M. Beraun: None. S.R. Akers: None. A.Y. Bagrov: None. W. Wei: None. E.G. Lakatta: None. O. Fedorova: None.
- © 2016 by American Heart Association, Inc.