Ellen G H M van den Heuvel1, Natasja M van Schoor2, Paul Lips3, Elke J P Magdeleyns4, Dorly J H Deeg5, Cees Vermeer6, Martin den Heijer7. 1. Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands; Royal FrieslandCampina, Amersfoort, The Netherlands. Electronic address: ellen.vandenheuvel@frieslandcampina.com. 2. Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands. Electronic address: Nm.vanschoor@vumc.nl. 3. Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands; Department of Internal Medicine and Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands. Electronic address: P.lips@vumc.nl. 4. VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. Electronic address: e.magdeleyns@vitak.com. 5. Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands. Electronic address: djh.deeg@vumc.nl. 6. VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. Electronic address: c.vermeer@vitak.com. 7. Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands; Department of Internal Medicine and Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands. Electronic address: M.denHeijer@vumc.nl.
Abstract
OBJECTIVES: Vitamin K plays a pivotal role in the synthesis of Matrix Gla protein (MGP), a calcification inhibitor in vascular tissue. Vascular calcification has become an important predictor of cardiovascular disease. The aim of the current study was to examine the potential association of circulating desphospho-carboxylated and -uncarboxylated MGP (dp-cMGP and dp-ucMGP), reflecting vitamin K status, with the incidence of cardiovascular events and disease (CVD) in older individuals. STUDY DESIGN: The study was conducted in 577 community-dwelling older men and women of the Longitudinal Aging Study Amsterdam (LASA), aged >55 year, who were free of cardiovascular disease at baseline. Multivariate Cox proportional hazards models were used to analyze the data. MAIN OUTCOME MEASURES: Incidence of CVD. RESULTS: After a mean follow-up of 5.6±1.2 year, we identified 40 incident cases of CVD. After adjustment for classical confounders and vitamin D status, we observed a more than 2-fold significantly higher risk of CVD for the highest tertile of dp-ucMGP with a HR of 2.69 (95% CI, 1.09-6.62) as compared with the lowest tertile. Plasma dp-cMGP was not associated with the risk of CVD. CONCLUSIONS: Vitamin K insufficiency, as assessed by high plasma dp-ucMGP concentrations is associated with an increased risk for cardiovascular disease independent of classical risk factors and vitamin D status. Larger epidemiological studies on dp-ucMGP and CVD incidence are needed followed by clinical trials to test whether vitamin K-rich diets will lead to a decreased risk for cardiovascular events.
OBJECTIVES:Vitamin K plays a pivotal role in the synthesis of Matrix Gla protein (MGP), a calcification inhibitor in vascular tissue. Vascular calcification has become an important predictor of cardiovascular disease. The aim of the current study was to examine the potential association of circulating desphospho-carboxylated and -uncarboxylated MGP (dp-cMGP and dp-ucMGP), reflecting vitamin K status, with the incidence of cardiovascular events and disease (CVD) in older individuals. STUDY DESIGN: The study was conducted in 577 community-dwelling older men and women of the Longitudinal Aging Study Amsterdam (LASA), aged >55 year, who were free of cardiovascular disease at baseline. Multivariate Cox proportional hazards models were used to analyze the data. MAIN OUTCOME MEASURES: Incidence of CVD. RESULTS: After a mean follow-up of 5.6±1.2 year, we identified 40 incident cases of CVD. After adjustment for classical confounders and vitamin D status, we observed a more than 2-fold significantly higher risk of CVD for the highest tertile of dp-ucMGP with a HR of 2.69 (95% CI, 1.09-6.62) as compared with the lowest tertile. Plasma dp-cMGP was not associated with the risk of CVD. CONCLUSIONS:Vitamin Kinsufficiency, as assessed by high plasma dp-ucMGP concentrations is associated with an increased risk for cardiovascular disease independent of classical risk factors and vitamin D status. Larger epidemiological studies on dp-ucMGP and CVD incidence are needed followed by clinical trials to test whether vitamin K-rich diets will lead to a decreased risk for cardiovascular events.
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