Research Progress of Warfarin-associated Vascular Calcification and Its Possible Therapy

Zhang, Yutao; Tang, Ze-Yao

doi:10.1097/fjc.0000000000000008

Cited by 18 publications

(17 citation statements)

References 61 publications

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“…Vitamin K antagonists such as warfarin are effectively used in risk reduction of venous and arterial thrombosis. They inhibit not only post-translational activation of vitamin K dependent coagulation factors but also synthesis or activation of many extrahepatic proteins and thus cause poorly known adverse effects seen both in animal experiments and human materials [5] [6].…”

Section: Discussionmentioning

confidence: 99%

“…An inverse correlation between the intake of vitamin K-2 (menaquinone) and vascular calcification has been reported in humans [1]- [3]. Warfarin, an antagonist of the vitamin K has been shown to induce arterial and cardiac valvular calcification presumably by inhibiting carboxylation and thus activation of two vitamin K-dependent proteins, Matrix Gla (MGP) and Growth Arrest Specific Gene 6 (Gas-6) proteins [4]- [6]. In murine models, warfarin treatment for a few weeks induces calcification of the artery wall and heart valves [7]- [9].…”

Section: Introductionmentioning

confidence: 99%

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Possible Correlation between INR and Serum Calcium

Helin¹,

Wickholm²,

Kautiainen³

et al. 2014

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Experimental and clinical studies have shown that long term anticoagulation therapy with warfarin can induce vascular calcification which is preventable by vitamin K. Osteoporosis has been shown to be associated with vascular calcification. In the present study, we wanted to see, whether INR (International Normalized Ratio), a measure of prothrombin time, and serum calcium (corrected by albumin) correlate in laboratory data of 94 anticoagulation patients on warfarin therapy. When adjusted on age and sex, there was an inverse correlation between the two variables. Clinical relevance of this observation and explanation of lowered calcium levels in blood parallel to increase in INR-values remain to be studied further.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Possible Correlation between INR and Serum Calcium

Helin¹,

Wickholm²,

Kautiainen³

et al. 2014

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“…Еще одной причиной негативного влияния варфарина на прогноз у больных с ФП и ХБП является его способность вызывать кальцификацию артерий, в том числе почечных [75,76].…”

Section: выбор антикоагулянтов у больных C неклапанной фп и хбпunclassified

Nonvalvular Atrial Fibrillation and Diabetic Nephropathy: Epidemiology, Prognosis, and Choice of Anticoagulant Therapy

Козиолова¹,

Polyanskaya²,

Суровцева³

et al. 2018

CARDIO

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Эпидемиология фибрилляции предсердий (ФП) и сахарного диабета (СД) 2-го типа Согласно эпидемиологическим исследованиям, СД 2-го типа в структуре коморбидной патологии является одним из наиболее частых сопутствующих заболеваний у больных неклапанной ФП [1]. Так, по данным регистра PREFER in AF, в Европе частота развития СД 2-го типа у пациентов с ФП дости-гает 23 % [2]. Результаты европейского пилотного регистра EORP-AF показали, что у больных с ФП распространенность СД 2-го типа составила 20,6 % [3]. При этом постоянная форма ФП встречалась достоверно чаще, чем пароксизмальная (21,5 % против 16 %; p=0,0022). Наибольшая распространенность СД 2-го типа среди больных с ФП представлена в регистре ORBIT AF, которая составила 29,5 % [4]. Согласно одной из европейских

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“…Vitamin K antagonists are frequently used in chronic haemodialysis patients, mainly for the prevention of stroke and systemic embolism in atrial fibrillation, a condition that is highly prevalent in this population [ 13 ]. Vitamin K antagonists are increasingly implicated in the development of VC [ 14 – 16 ], precisely because they block not only the gamma-carboxylation of coagulation factors, but also prevent the activation of MGP. The use of anticoagulants alternative to warfarin has been problematic in the dialysis population for lack of data, given their substantial renal clearance.…”

Section: Background and Objectivesmentioning

confidence: 99%

The effects of vitamin K supplementation and vitamin K antagonists on progression of vascular calcification: ongoing randomized controlled trials

et al. 2015

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BackgroundThe 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. New oral anticoagulants (NOACs) are valuable alternatives to vitamin K antagonists in the general population, but their use in dialysis has been encumbered by substantial renal clearance. However, a recent pharmacokinetic study provided information on how to use rivaroxaban in haemodialysis patients.MethodsWe conduct a randomized, prospective, multicentre, open-label interventional clinical trial that will include 117 chronic haemodialysis patients with non-valvular atrial fibrillation, treated with or candidates for treatment with vitamin K antagonists. Patients will be randomized to a vitamin K antagonist titrated weekly to an international normalized ratio between 2 and 3, a daily dose of rivaroxaban of 10 mg, or a daily dose of rivaroxaban 10 mg with a thrice weekly supplement of 2000 µg vitamin K2. Cardiac computed tomography, pulse wave velocity (PWV) measurements and MGP sampling will be performed at baseline, 6 months, 12 months and 18 months. Primary endpoints include progression of coronary artery and thoracic aorta calcification and changes in PWV. Secondary endpoints are progression of aortic and mitral valve calcification, all-cause mortality, major adverse cardiovascular events, stroke and bleeding. The ClinicalTrials.gov database was searched to retrieve related trials.ResultsSeven trials, three of which are performed in the haemodialysis population, evaluate whether pharmacological doses of vitamin K1 or K2 retard progression of VC. Five studies compare the effect of warfarin and NOACs on progression of VC, the present study being the only conducted in the dialysis population.ConclusionVitamin K deficiency may be a modifiable cardiovascular risk factor in the haemodialysis population. Conversely, vitamin K antagonists may aggravate VC burden in haemodialysis patients. Several ongoing trials may provide an answer to these questions in the near future.

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Research Progress of Warfarin-associated Vascular Calcification and Its Possible Therapy

Cited by 18 publications

References 61 publications

Possible Correlation between INR and Serum Calcium

Possible Correlation between INR and Serum Calcium

Nonvalvular Atrial Fibrillation and Diabetic Nephropathy: Epidemiology, Prognosis, and Choice of Anticoagulant Therapy

The effects of vitamin K supplementation and vitamin K antagonists on progression of vascular calcification: ongoing randomized controlled trials

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