Warfarin, but not rivaroxaban, promotes the calcification of the aortic valve in ApoE−/− mice

Rattazzi, Marcello; Faggin, Elisabetta; Bertacco, Elisa; Nardin, Chiara; Pagliani, Leopoldo; Plebani, Mario; Cinetto, Francesco; Guidolin, Diego; Puato, Massimo; Pauletto, Paolo

doi:10.1111/1755-5922.12438

“…According to cross-sectional studies, the amount of ingested phylloquinone or menaquinones was predictive of coronary artery calcification [56,57]. Rattazzi et al provided evidence that warfarin, a vitamin K antagonist, worsened aortic valve calcification in a mouse model of atherosclerosis [58]. Vitamin K supplements attenuated vascular calcification by suppressing Toll-like receptors in an atherosclerosis animal model [59].…”

Section: Introductionmentioning

confidence: 99%

Emerging Role of Vitamins D and K in Modulating Uremic Vascular Calcification: The Aspect of Passive Calcification

Hou

¹

,

Lu

²

,

Zheng

³

et al. 2019

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Vascular calcification is a critical complication in patients with chronic kidney disease (CKD) because it is predictive of cardiovascular events and mortality. In addition to the traditional mechanisms associated with endothelial dysfunction and the osteoblastic transformation of vascular smooth muscle cells (VSMCs), the regulation of calcification inhibitors, such as calciprotein particles (CPPs) and matrix vesicles plays a vital role in uremic vascular calcification in CKD patients because of the high prevalence of vitamin K deficiency. Vitamin K governs the gamma-carboxylation of matrix Gla protein (MGP) for inhibiting vascular calcification, and the vitamin D binding protein receptor is related to vitamin K gene expression. For patients with chronic kidney disease, adequate use of vitamin D supplements may play a role in vascular calcification through modulation of the calciprotein particles and matrix vesicles (MVs).

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“…16 Recent studies have shown a high association of Warfarin therapy and the occurrence of aortic valvular calcification. 17,18 Warfarin leads to calcification influencing the synthesis and function of the matrix Gla-protein, which is otherwise an inhibitor of the calcification process. 16,18 Taking everything mentioned together, it might be that the haemodynamic and mechanical forces along with oxidized lipids and exogenous substances (e.g., bacterial lipopolysaccharides) transform calm VICs into activated VICs.…”

Section: Presence Of Metaplasiamentioning

confidence: 99%

Bone and cartilage metaplasia in calcific aortic stenosis

Zorić

¹

,

Vuković

²

,

Lovrenski

³

et al. 2021

VOJNOSANIT PREGL

1

0

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Background/ Aim. Recent studies have shown that process of aortic calcification is often active and closely related to the formation of bone tissue in calcific aortic stenosis. The aim was to analyze the demographic characteristics of patients with calcified aortic stenosis, the most common symptoms, comorbidities and risk factors, incidence of bone and cartilage metaplasia and its possible association with the present comorbidities, as well as its clinical importance. Methods. We retrospectively analyzed the medical records of 115 patients reffered to the University Hospital from January 2013 to December 2015. Results. Calcific aortic stenosis occured more frequently in males. The average age of patients was 67.3 years. The majority of patients were non-smokers, overweight. The most common clinical symptoms were fatigue, shortness of breath and chest pain. Eighteen patients (15.6%) had no symptoms. Seventeen patients (14.8%) had cartilaginous and osseous metaplasia. Gender, age, smoking and BMI (Body Mass Index) had the same distribution among patients with and without metaplasia. Metaplasia was equally prevalent among patients with moderate, severe and critical aortic stenosis. Conclusions. Age, sex, smoking, BMI and blood pressure values are not risk factors neither for osseous nor for cartilaginous metaplasia.

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“…Our study was motivated by previous reports which have implicated VKA treatment in increased atherosclerotic calcification, plaque formation, and renal microvasculature damage . Although robust clinical data on this “renovascular calcification hypothesis” are limited, its implications are considerable because millions of patients globally are treated with VKA for prevention of stroke/systemic embolism in atrial fibrillation .…”

Section: Discussionmentioning

confidence: 99%

“…In this retrospective analysis of prospectively collected routine healthcare data in the primary care setting, we examined the im- Our study was motivated by previous reports which have implicated VKA treatment in increased atherosclerotic calcification, plaque formation, and renal microvasculature damage. 6,8,16 Although robust clinical data on this "renovascular calcification hypothesis" are limited, its implications are considerable because millions of patients globally are treated with VKA for prevention of stroke/systemic embolism in atrial fibrillation. 2,17 Our clinical data support this hypothesis by showing a statistically significant excess in kidney function loss in VKA patients, although the absolute impact was only small.…”

Section: Discussionmentioning

confidence: 99%

Exposure to vitamin k antagonists and kidney function decline in patients with atrial fibrillation and chronic kidney disease

Posch

¹

,

Ay

²

,

Stöger

³

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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Background Exposure to vitamin K antagonists ( VKA ) has been suggested to accelerate progression of chronic kidney disease ( CKD ) but robust clinical data are currently lacking. Methods We retrospectively evaluated the impact of VKA exposure on kidney function in patients with atrial fibrillation ( AF ) and CKD stage 3/4. Patients were prospectively followed within a primary care electronic database (median follow‐up of 1.45 years). The kidney function trajectory over time, defined as the annualized change in estimated glomerular filtration rate ( eGFR ), was analyzed with linear mixed‐effects regression including propensity score adjustment. Results 14 432 patients (median age 78 years, median CHA 2 DS 2 ‐ VAS c score 4 points) contributed 97 792 eGFR measurements (mean 6.8 measurements/patient; range: 1‐197). Mean baseline eGFR was 50.3 mL/min/1.73 m 2 ; and declined by 1.10 mL/min/1.73 m 2 /year (95% CI : 0.91‐1.28, P < 0.0001). In 7409 patients with VKA exposure, CKD progression was significantly faster compared to patients without VKA exposure (5‐year absolute eGFR loss from baseline: 6.0 mL/min/1.73 m 2 vs 4.5 mL/min/1.73 m 2 , for an absolute 5‐year excess eGFR decline with VKA exposure of 1.5 mL/min/1.73 m 2 (95% CI : 0.4‐2.7, P = 0.002). These results prevailed upon adjusting for CHA 2 DS 2 ‐ VAS c score and other potential imbalances in prognostic variables, and in several sensitivity analyses. In the group without documented VKA exposure, 1775 VKA patients (24%) and 1012 patients (14%) developed a 30% decline in eGFR during follow‐up ( P < 0.0001). Conclusions In patients with AF and CKD , VKA use is associated with accelerated eGFR decline. Within the limitations of a retrospective analysis, this finding supports the “ VKA ‐renal‐calcification hypothesis.” However, although statistically significant, the exces...

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Warfarin, but not rivaroxaban, promotes the calcification of the aortic valve in ApoE−/− mice

Cited by 33 publications

References 26 publications

Emerging Role of Vitamins D and K in Modulating Uremic Vascular Calcification: The Aspect of Passive Calcification

Emerging Role of Vitamins D and K in Modulating Uremic Vascular Calcification: The Aspect of Passive Calcification

Bone and cartilage metaplasia in calcific aortic stenosis

Exposure to vitamin k antagonists and kidney function decline in patients with atrial fibrillation and chronic kidney disease

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