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Warfarin and vascular calcification

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https://www.readbyqxmd.com/read/29716795/metformin-prevents-the-development-of-severe-chronic-kidney-disease-and-its-associated-mineral-and-bone-disorder
#1
Ellen Neven, Benjamin Vervaet, Kerstin Brand, Ulrike Gottwald-Hostalek, Britt Opdebeeck, Annelies De Maré, Anja Verhulst, Jean-Daniel Lalau, Said Kamel, Marc E De Broe, Patrick C D'Haese
Chronic kidney disease (CKD) causes dysregulation of mineral metabolism, vascular calcification and renal osteodystrophy, an entity called 'CKD-Mineral and Bone Disorder' (CKD-MBD). Here we determine whether metformin, an anti-diabetic drug, exerts favorable effects on progressive, severe CKD and concomitant mineral metabolism disturbances. Rats with CKD-MBD, induced by a 0.25% adenine diet for eight weeks, were treated with 200 mg/kg/day metformin or vehicle from one week after CKD induction onward. Severe, stable CKD along with marked hyperphosphatemia and hypocalcemia developed in these rats which led to arterial calcification and high bone turnover disease...
April 28, 2018: Kidney International
https://www.readbyqxmd.com/read/29395943/warfarin-accelerated-vascular-calcification-and-worsened-cardiac-dysfunction-in-remnant-kidney-mice
#2
Ming-Tsun Tsai, Ying-Ying Chen, Wei-Jeng Chang, Szu-Yuan Li
BACKGROUND: Vascular calcification is highly prevalent in end-stage renal disease (ESRD) and is a significant risk factor for future cardiovascular events and death. Warfarin use results in dysfunction of matrix Gla protein, an inhibitor of vascular calcification. However, the effect of warfarin on vascular calcification in patients with ESRD is still not well characterized. Thus we investigated whether arterial calcification can be accelerated by warfarin treatment both in vitro and in vivo using a mouse remnant kidney model...
April 2018: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/29353071/effects-of-warfarin-on-biological-processes-other-than-haemostasis-a-review
#3
REVIEW
Aleksandra Popov Aleksandrov, Ivana Mirkov, Marina Ninkov, Dina Mileusnic, Jelena Demenesku, Vesna Subota, Dragan Kataranovski, Milena Kataranovski
Warfarin is the world's most widely used anticoagulant drug. Its anticoagulant activity is based on the inhibition of the vitamin K-dependent (VKD) step in the complete synthesis of a number of blood coagulation factors that are required for normal blood coagulation. Warfarin also affects synthesis of VKD proteins not related to haemostasis including those involved in bone growth and vascular calcification. Antithrombotic activity of warfarin is considered responsible for some aspects of its anti-tumour activity of warfarin...
March 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29147170/clinical-assessment-of-warfarin-therapy-in-patients-with-maintenance-dialysis-clinical-efficacy-risks-and-development-of-calciphylaxis
#4
Hajime Hasegawa
Recent years, multiple studies regarding clinical efficacy and risks of Warfarin therapy in dialysis patients have been reported, and not a few reports conclude that clinical advantage of Warfarin is questionable in dialysis patients. Conversely, its hemorrhagic risk might be a little more serious in dialysis patients comparing to non-dialysis patients. Basically, it is assumed that long-term administration of Warfarin accelerates the development of vascular athelosclerosis because of the abolished anti-calcification effect of Gla-protein activation by decreased vitamin K activity...
September 25, 2017: Annals of Vascular Diseases
https://www.readbyqxmd.com/read/28703931/rationale-and-design-of-a-randomized-trial-of-apixaban-vs-warfarin-to-evaluate-atherosclerotic-calcification-and-vulnerable-plaque-progression
#5
Kazuhiro Osawa, Rine Nakanishi, Theingi Tiffany Win, Dong Li, Sina Rahmani, Negin Nezarat, Nasim Sheidaee, Matthew J Budoff
Vitamin K antagonists (VKAs) are known to increase vascular calcification, suggesting increased cardiovascular disease events. Apixaban is an oral direct factor Xa inhibitor superior to warfarin at preventing stroke or systemic embolism and may stabilize coronary atherosclerosis. The potential benefits of avoiding VKA therapy and the favorable effects of factor Xa inhibitors could contribute to cardiovascular disease event reduction. We hypothesized that apixaban inhibits vascular calcification and coronary atherosclerosis progression compared with warfarin in patients with atrial fibrillation (AF)...
July 13, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28698808/vitamins-k1-and-k2-the-emerging-group-of-vitamins-required-for-human-health
#6
REVIEW
Gerry Kurt Schwalfenberg
OBJECTIVE: To review the evidence for the use of vitamin K supplementation in clinical conditions such as osteoporosis, vascular calcification, arthritis, cancer, renal calculi, diabetes, and warfarin therapy. QUALITY OF EVIDENCE: PubMed was searched for articles on vitamin K (K1 and K2) along with books and conference proceedings and health conditions listed above. Level I and II evidence supports the use of vitamins K1 and K2 in osteoporosis and Level II evidence supports vitamin K2 in prevention of coronary calcification and cardiovascular disease...
2017: Journal of Nutrition and Metabolism
https://www.readbyqxmd.com/read/28657840/therapeutic-warfarin-use-and-the-extrahepatic-functions-of-vitamin-k-dependent-proteins
#7
C J Donaldson, D J Harrington
The impact of warfarin therapy on the functions of extrahepatic vitamin K-dependent proteins (VKDP) is less clearly understood and less widely recognised in clinical practice than that on the hepatic counterparts (clotting factors II, VII, IX and X). Warfarin inhibits osteocalcin, an abundant extrahepatic VKDP involved in the mineralisation and maturation of bone and thus, primarily by this mechanism, may have an adverse effect on bone health. Whilst some studies do link warfarin use to an increase in osteoporosis and fracture risk others have not...
October 2017: British Journal of Biomedical Science
https://www.readbyqxmd.com/read/28639365/vascular-calcification-vitamin-k-and-warfarin-therapy-possible-or-plausible-connection
#8
REVIEW
Aino Siltari, Heikki Vapaatalo
Atherosclerosis is a pathological process underpinning many cardiovascular diseases; it is the main cause of global mortality. Atherosclerosis is characterized by an invasion of inflammatory cells, accumulation of lipids and the formation of fatty streaks (plaques) which subsequently allow accumulation of calcium and other minerals leading to a disturbance in the vascular endothelium and its regulatory role in arterial function. Vascular calcification is a different process, stringently regulated mainly by local factors, in which osteoblast-like cells accumulate in the muscular layer of arteries ultimately taking on the physiological appearance of bone...
January 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28553032/stroke-in-patients-with-chronic-kidney-disease%C3%A2-how-do-we-approach-and-manage-it
#9
REVIEW
S Nayak-Rao, M P Shenoy
Renal failure is a potent risk factor for stroke, which is a leading cause of morbidity and mortality worldwide. The risk of stroke is 5-30 times higher in patients with chronic kidney disease (CKD), especially on dialysis. Case fatality rates are also higher reaching almost 90%. It is therefore important to understand the factors that predispose to stroke in this vulnerable population to better apply preventive strategies. The heightened risk of stroke in CKD represents the interplay of the vascular co-morbidities that occur with renal impairment and factors specific to renal failure such as malnutrition-inflammation-atherosclerosis complex, the effect of uremic toxins, dialysis techniques, vascular access, and the use of anticoagulants to maintain flow in the extracorporeal circuit...
May 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28290837/-the-choice-of-anticoagulant-therapy-in-patients-with-non-valvular-atrial-fibrillation-and-chronic-kidney-disease
#10
N A Koziolova, E A Polyanskaya, I I Kolegova
The review shows the prevalence of atrial fibrillation (AF) in patients with chronic kidney disease (CKD), depending on the severity of the disease. Patients with non-valvular AF and CKD have a significantly increased risk of both bleeding and thromboembolic complications, and death from all causes. Evaluation of the results of randomized clinical trials (RCTs), meta-analyzes of RCTs demonstrated the advantages of the new oral anticoagulants (NOAC), such as dabigatran, rivaroxaban, apixaban, compared with warfarin in reducing the risk of bleeding in patients with AF and CKD in predialysis stage...
January 2017: Kardiologiia
https://www.readbyqxmd.com/read/28276631/antithrombotic-medications-in-dialysis-patients-a-double-edged-sword
#11
REVIEW
Georgios Vlachopanos, Farid Girgis Ghalli
In the clinical context of end-stage renal disease (ESRD), thrombosis and bleeding risks are simultaneously increased and may have devastating consequences. While anticoagulant and antiplatelet drugs are indispensable for the prevention of thromboembolic events, the significantly higher bleeding risk makes their handling extremely complicated. In ESRD, they are frequently administered for a wide array of conditions. For example, atrial fibrillation is quite common in ESRD and warrants the use of anticoagulants like warfarin...
February 2017: Journal of Evidence-based Medicine
https://www.readbyqxmd.com/read/28214287/association-of-warfarin-with-congestive-heart-failure-and-peripheral-artery-occlusive-disease-in-hemodialysis-patients-with-atrial-fibrillation
#12
Kuo-Hua Lee, Szu-Yuan Li, Jin-Sin Liu, Chi-Ting Huang, Ying-Ying Chen, Yao-Ping Lin, Chih-Cheng Hsu, Der-Cherng Tarng
BACKGROUND: The effect of warfarin on the risk of cardiovascular (CV) disease is unknown among chronic hemodialysis patients with atrial fibrillation (HD-AF). METHODS: Population-based propensity score and prescription time-distribution matched cohort study including 6719 HD-AF patients with CHA 2 DS 2 -VASc score ≥ 2 were divided into warfarin users and nonusers and followed-up for CV events and death. RESULTS: Warfarin treatment in HD-AF patients with AF preceding HD was associated with higher risks of developing congestive heart failure [hazard ratio (HR)=1...
May 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28104608/prothrombin-loading-of-vascular-smooth-muscle-cell-derived-exosomes-regulates-coagulation-and-calcification
#13
Alexander N Kapustin, Michael Schoppet, Leon J Schurgers, Joanne L Reynolds, Rosamund McNair, Alexander Heiss, Willi Jahnen-Dechent, Tilman M Hackeng, Georg Schlieper, Paul Harrison, Catherine M Shanahan
OBJECTIVE: The drug warfarin blocks carboxylation of vitamin K-dependent proteins and acts as an anticoagulant and an accelerant of vascular calcification. The calcification inhibitor MGP (matrix Gla [carboxyglutamic acid] protein), produced by vascular smooth muscle cells (VSMCs), is a key target of warfarin action in promoting calcification; however, it remains unclear whether proteins in the coagulation cascade also play a role in calcification. APPROACH AND RESULTS: Vascular calcification is initiated by exosomes, and proteomic analysis revealed that VSMC exosomes are loaded with Gla-containing coagulation factors: IX and X, PT (prothrombin), and proteins C and S...
March 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28049648/vitamin-k-dependent-carboxylation-of-matrix-gla-protein-influences-the-risk-of-calciphylaxis
#14
Sagar U Nigwekar, Donald B Bloch, Rosalynn M Nazarian, Cees Vermeer, Sarah L Booth, Dihua Xu, Ravi I Thadhani, Rajeev Malhotra
Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vitamin K deficiency on MGP carboxylation. Our study included 20 patients receiving hemodialysis with calciphylaxis (cases) and 20 patients receiving hemodialysis without calciphylaxis (controls) matched for age, sex, race, and warfarin use...
June 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27927630/inactive-matrix-gla-protein-and-arterial-stiffness-in-type-2-diabetes-mellitus
#15
MULTICENTER STUDY
Mayank Sardana, Izzah Vasim, Swapna Varakantam, Uzma Kewan, Ali Tariq, Maheshwara R Koppula, Amer Ahmed Syed, Melissa Beraun, Nadja E A Drummen, Cees Vermeer, Scott R Akers, Julio A Chirinos
BACKGROUND: Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes...
February 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/27673645/can-vascular-calcification-be-associated-with-warfarin-treatment
#16
A Siltari, T Helin, N Wickholm, R Lassila, R Korpela, H Kautiainen, H Vapaatalo
No abstract text is available yet for this article.
October 6, 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27412937/-mechanism-of-losartan-suppressing-vascular-calcification-in-rat-aortic-artery
#17
Juan Shao, Panfeng Wu, Jiliang Wu, Mincai Li
Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week...
August 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27254816/the-role-of-vitamin-k-in-vascular-calcification-of-patients-with-chronic-kidney-disease
#18
REVIEW
Julie Wuyts, Annemieke Dhondt
Patients with chronic kidney disease (CKD) are prone to vascular calcification. Pathogenetic mechanisms of vascular calcifications have been broadly studied and discussed such as the role of hyperphosphatemia, hypercalcemia, parathormone, and vitamin D. In recent years, new insights have been gained pointing to vitamin K as a main actor. It has been discovered that vitamin K is an essential cofactor for the activation of matrix Gla protein (MGP), a calcification inhibitor in the vessel wall. Patients with CKD often suffer from vitamin K deficiency, resulting in low active MGP and eventually a lack of inhibition of vascular calcification...
December 2016: Acta Clinica Belgica
https://www.readbyqxmd.com/read/27230889/gas6-protein-its-role-in-cardiovascular-calcification
#19
Nadine Kaesler, Svenja Immendorf, Chun Ouyang, Marjolein Herfs, Nadja Drummen, Peter Carmeliet, Cees Vermeer, Jürgen Floege, Thilo Krüger, Georg Schlieper
BACKGROUND: Cardiovascular calcifications can be prevented by vitamin K and are accelerated by vitamin K antagonists. These effects are believed to be mainly mediated by the vitamin K-dependent matrix Gla protein. Another vitamin K-dependent protein, Gas6, is also expressed in vascular smooth muscle cells (VSMC). In vitro Gas6 expression was shown to be regulated in VSMC calcification and apoptotic processes. METHODS: We investigated the role of Gas6 in vitro using VSMC cultures and in vivo in young and old Gas6-deficient (Gas6(-/-)) and wildtype (WT) mice...
May 26, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27203170/-vascular-calcifications-the-hidden-side-effects-of-vitamin-k-antagonists
#20
REVIEW
Youssef Bennis, Subashini Vengadessane, Sandra Bodeau, Valérie Gras, Giampiero Bricca, Saïd Kamel, Sophie Liabeuf
Despite the availability of new oral anticoagulants, vitamin K antagonists (VKA, such as fluindione, acenocoumarol or warfarin) remain currently the goal standard medicines for oral prevention or treatment of thromboembolic disorders. They inhibit the cycle of the vitamin K and its participation in the enzymatic gamma-carboxylation of many proteins. The VKA prevent the activation of the vitamin K-dependent blood clotting factors limiting thus the initiation of the coagulation cascade. But other proteins are vitamin K-dependent and also remain inactive in the presence of VKA...
September 2016: Thérapie
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