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Hypertension. 2015 Jul;66(1):85-92. doi: 10.1161/HYPERTENSIONAHA.115.05177. Epub 2015 May 18.

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population-Based Study.

Author information

1
From the Division of Chronic Disease, University Institute of Social and Preventive Medicine (IUMSP) (E.P., F.P., M. Bochud, I.G.), and Department of Medicine, Service of Nephrology and Hypertension, (M.P., M. Burnier), University Hospital of Lausanne (CHUV), Lausanne, Switzerland; Service of Nephrology, Department of Specialties (B.P., P.-Y.M.), and Unit of Population Epidemiology, Department of Community Medicine and Primary Care and Emergency Medicine (I.G.), University Hospital of Geneva, Geneva, Switzerland; University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland (D.A., M.M., B.V.); Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospitals, Geneva, Switzerland and Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD (G.E.); Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium (Y.-P.L., J.A.S.); R&D Group VitaK, Maastricht University, Maastricht, The Netherlands (N.E.A.D., M.H.J.K., C.V.); and Hypertension Unit, Department of Specialties, University Hospitals of Geneva, Geneva, Switzerland (A.P.-B.).
2
From the Division of Chronic Disease, University Institute of Social and Preventive Medicine (IUMSP) (E.P., F.P., M. Bochud, I.G.), and Department of Medicine, Service of Nephrology and Hypertension, (M.P., M. Burnier), University Hospital of Lausanne (CHUV), Lausanne, Switzerland; Service of Nephrology, Department of Specialties (B.P., P.-Y.M.), and Unit of Population Epidemiology, Department of Community Medicine and Primary Care and Emergency Medicine (I.G.), University Hospital of Geneva, Geneva, Switzerland; University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland (D.A., M.M., B.V.); Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospitals, Geneva, Switzerland and Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD (G.E.); Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium (Y.-P.L., J.A.S.); R&D Group VitaK, Maastricht University, Maastricht, The Netherlands (N.E.A.D., M.H.J.K., C.V.); and Hypertension Unit, Department of Specialties, University Hospitals of Geneva, Geneva, Switzerland (A.P.-B.). Murielle.Bochud@chuv.ch.

Abstract

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.

KEYWORDS:

calcium-binding protein; matrix Gla-protein; pulse wave velocity; vascular stiffness; vitamin K

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