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Warfarin and vascular calcification

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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
#1
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
#2
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
#3
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...
June 28, 2017: British Journal of Biomedical Science
https://www.readbyqxmd.com/read/28639365/vascular-calcification-vitamin-k-and-warfarin-therapy-possible-or-plausible-connection
#4
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...
June 21, 2017: 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
#5
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
#6
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
#7
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
#8
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 CHA2DS2-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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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...
2016: BMC Nephrology
https://www.readbyqxmd.com/read/27203170/-vascular-calcifications-the-hidden-side-effects-of-vitamin-k-antagonists
#16
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
https://www.readbyqxmd.com/read/27079417/atrial-fibrillation-in-dialysis-patients-time-to-abandon-warfarin
#17
REVIEW
Diego Brancaccio, Luca Neri, Francesco Bellocchio, Carlo Barbieri, Claudia Amato, Flavio Mari, Bernard Canaud, Stefano Stuard
Atrial fibrillation (AF) is a frequent clinical complication in dialysis patients, and warfarin therapy represents the most common approach for reducing the risk of stroke in this population. However, current evidence based on observational studies, offer conflicting results, whereas no randomized controlled trials have been carried out so far. Additionally, many clinicians are wary of the possible role of warfarin as vascular calcification inducer and its potential to increase the high risk of bleeding among patients on dialysis...
May 16, 2016: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/26985380/the-effects-of-vitamin-k-supplementation-and-vitamin-k-antagonists-on-progression-of-vascular-calcification-ongoing-randomized-controlled-trials
#18
Rogier Caluwé, Lotte Pyfferoen, Koen De Boeck, An S De Vriese
BACKGROUND: The extent and the progression of vascular calcification (VC) are independent predictors of cardiovascular risk in the haemodialysis population. Vitamin K is essential for the activation of matrix gla protein (MGP), a powerful inhibitor of tissue calcification. Functional vitamin K deficiency may contribute to the high VC burden in haemodialysis patients. In addition, haemodialysis patients are frequently treated with vitamin K antagonists, mainly to prevent stroke in atrial fibrillation, potentially compounding the cardiovascular risk in these already vulnerable patients...
April 2016: Clinical Kidney Journal
https://www.readbyqxmd.com/read/26890570/high-serum-sclerostin-levels-are-associated-with-a-better-outcome-in-haemodialysis-patients
#19
Guillaume Jean, Charles Chazot, Eric Bresson, Eric Zaoui, Etienne Cavalier
BACKGROUND: Sclerostin is an osteocyte hormone that decreases osteoblastogenesis. Sclerostin may play a key role in osteoporosis and also in vascular calcification (VC). In chronic kidney disease and haemodialysis (HD) patients, serum sclerostin levels are high. AIM: To assess the correlation of serum sclerostin levels with VC, bone mineral density (BMD), and survival rate in HD patients. METHODS: A cross-sectional study was conducted in prevalent HD patients to correlate serum sclerostin tertiles with the Kauppila aortic calcification score, BMD scores and survival rate...
2016: Nephron
https://www.readbyqxmd.com/read/26811161/increased-peripheral-arterial-calcification-in-patients-receiving-warfarin
#20
Kum Hyun Han, W Charles O'Neill
BACKGROUND: Matrix Gla protein is a vitamin K-dependent inhibitor of vascular calcification. Warfarin use is associated with increased breast arterial calcification, but whether this is reflective of other arteries or occurs in men is unclear. In this study, the prevalence of calcification in peripheral arteries was compared in patients with and without warfarin therapy. METHODS AND RESULTS: This retrospective matched cohort study assessed 430 patients with radiographs performed during or after warfarin therapy who were identified by a computerized search of medical records...
January 25, 2016: Journal of the American Heart Association
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