Vitamin K Status and Vascular Calcification: Evidence from Observational and Clinical Studies

Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem NC, USA.
Advances in Nutrition (Impact Factor: 4.71). 03/2012; 3(2):158-65. DOI: 10.3945/an.111.001644
Source: PubMed


Vascular calcification occurs when calcium accumulates in the intima (associated with atherosclerosis) and/or media layers of the vessel wall. Coronary artery calcification (CAC) reflects the calcium burden within the intima and media of the coronary arteries. In population-based studies, CAC independently predicts cardiovascular disease (CVD) and mortality. A preventive role for vitamin K in vascular calcification has been proposed based on its role in activating matrix Gla protein (MGP), a calcification inhibitor that is expressed in vascular tissue. Although animal and in vitro data support this role of vitamin K, overall data from human studies are inconsistent. The majority of population-based studies have relied on vitamin K intake to measure status. Phylloquinone is the primary dietary form of vitamin K and available supplementation trials, albeit limited, suggest phylloquinone supplementation is relevant to CAC. Yet observational studies have found higher dietary menaquinone, but not phylloquinone, to be associated with less calcification. Vascular calcification is highly prevalent in certain patient populations, especially in those with chronic kidney disease (CKD), and it is plausible vitamin K may contribute to reducing vascular calcification in patients at higher risk. Subclinical vitamin K deficiency has been reported in CKD patients, but studies linking vitamin K status to calcification outcomes in CKD are needed to clarify whether or not improving vitamin K status is associated with improved vascular health in CKD. This review summarizes the available evidence of vitamin K and vascular calcification in population-based studies and clinic-based studies, with a specific focus on CKD patients.

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    • "Oral anticoagulants inhibit vitamin K epoxide reductase, thereby preventing vitamin K from recycling back to its active form resulting in a hypocoaguable state. Aside from the impact on clotting, vitamin K has also been shown to both impair the physiological effect of osteocalcin, which regulates bone mineralization, and activate the Matrix G1A protein (MGP) which inhibits calcification in vascular tissue [3] [4] [5] [6]. A deficiency in active vitamin K through long-term utilization of warfarin may result in increased vascular calcification [7]. "
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    ABSTRACT: Introduction. A deficiency in vitamin K through the utilization of warfarin may result in increased vascular calcification and complications. This study aimed to determine the impact of warfarin administration on patients with end stage renal disease (ESRD) in a large, national sample. Methods. A retrospective analysis using the 2005–2010 National Inpatient Sample (NIS), a part of the Health Care Utilization Project (HCUP), was completed using ICD-9 diagnosis codes to capture patients with ESRD prescribed and not prescribed warfarin. Statistical analysis was through ANOVA and chi-squared testing. Results. From 2005–2010, 927,814 patients with ESRD were identified nationally. 3.5% (32,737) were prescribed warfarin. Patients prescribed warfarin had an average age of 64 years and 51% were male. For every comorbid condition (amputation, congestive heart failure, chronic obstructive pulmonary disorder, cerebrovascular accident, diabetes, hypertension, myocardial infarction, peripheral vascular diasese, and valvular disease) patients prescribed Warfarin had significantly higher rates of disease as compared to their nonwarfarin ESRD counterparts. ESRD patients prescribed warfarin had significantly shorter length of stay but increased hospital charges. They were more likely to be discharged to home and had significantly decreased in-hospital mortality. Conclusion. Patients with ESRD taking warfarin are more likely to have comorbidities and/or complications but have a decreased LOS and in-hospital mortality compared to their ESRD counterparts not administered warfarin.
    Full-text · Article · Sep 2014 · Vascular Medicine
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    • "Menaquinone-7, also known as vitamin K2, is a lipid-soluble molecule that, in humans, plays a crucial role in blood coagulation, bone metabolism, and calcification of arteries [1] [2] [3] [4] [5] [6]. Bacteria of the large intestine synthesize menaquinone-7 (hereafter simplified to ''menaquinone'') for use as an electron transporter in anaerobic respiration [7] [8]. "
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    ABSTRACT: The function of a Bacteroidetes menaquinone biosynthetic pathway fusion protein comprised of an N-terminal haloacid dehalogenase (HAD) family domain and a C-terminal hotdog-fold family domain is described. Whereas the thioesterase domain efficiently catalyzes 1,4-dihydroxynapthoyl-CoA hydrolysis, an intermediate step in the menaquinone pathway, the HAD domain is devoid of catalytic activity. In some Bacteroidetes a homologous, catalytically active 1,4-dihydroxynapthoyl-CoA thioesterase replaces the fusion protein. Following the gene fusion event, sequence divergence resulted in a HAD domain that functions solely as the oligomerization domain of an otherwise inactive thioesterase domain.
    Full-text · Article · Jul 2013 · FEBS letters
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    ABSTRACT: Background: Vitamin K antagonists not only influence the synthesis of coagulation factors but also the activation of other vitamin K dependent proteins. Among other possible side effects, arterial calcification has been focused on in recent years. History and findings: Four patients under long-term anticoagulation for more than 10 years developed medial calcific sclerosis. In case 1 we identified an unexplained medial calcific sclerosis on x-ray after a trauma by chance. After that we examined the ankle-brachial index of blood pressure in all patients who had received long-term anticoagulation for more than 10 years. Where the index exceeded 1,3 we performed a x-ray-examination of the forefoot. Of the four described patients no one suffered from diabetes mellitus, renal failure or hyperparathyreoidism. Serum calcium was normal in all patients. The severity of the medial calcific sclerosis could not be explained by the initial vascular risk factors. Conclusion: In certain patients, even at low vascular risk, a medial calcific sclerosis can appear under long-term anticoagulation with vitamin K antagonists. We conclude that vitamin K antagonists inhibit several proteins which protect the vessels from calcification leading to medial calcific sclerosis.
    No preview · Article · May 2013 · DMW - Deutsche Medizinische Wochenschrift
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