Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial

Lindholt, Jes Sanddal; Frandsen, Niels Erik; Fredgart, Maise Høigaard; Øvrehus, Kristian Altern; Dahl, Jordi S.; Møller, Jacob Eifer; Folkestad, Lars; Urbonavičienė, Gražina; Becker, S; Lambrechtsen, Jess; Auscher, Søren; Hosbond, Susanne; Alan, Dilek Hunerel; Rasmussen, Lars Melholt; Gerke, Oke; Mickley, Hans; Diederichsen, Axel Cosmus Pyndt

doi:10.1136/bmjopen-2018-022019

Cited by 19 publications

(19 citation statements)

References 37 publications

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“…Now an on-going double-blinded, randomized, placebo-controlled trial investigates the difference in progression of CAC score in patients with CAD randomized to either vitamin K2 supplementation or placebo [ 32 ]. A similar on-going study seeks to examine if vitamin K2 supplementation can slow down the calcification of aortic valves in patients with substantial aortic valve calcification [ 33 ]. These studies will hopefully add knowledge on the importance of vitamin K in tissue calcification.…”

Section: Discussionmentioning

confidence: 99%

Extent of arterial calcification by conventional vitamin K antagonist treatment

et al. 2020

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Background and aims Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD). Methods We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007–2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1–99, 100–399, ≥400) was investigated by ordered logistic regression adjusting for covariates. Results The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009–1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935–1.074). There was no significant interaction between VKA treatment duration and age on CAC category. Conclusions Adjusted for cardiovascular risk factors, VKA treatment–contrary to NOAC—was associated to higher CAC category.

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Section: Discussionmentioning

confidence: 99%

Extent of arterial calcification by conventional vitamin K antagonist treatment

et al. 2020

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“…The protective effect of vitamin K 1 supplementation is particularly evident in dialysis patients. In such patients, both a reduction of dp-ucMGP plasma levels and reduced arterial stiffness could be achieved [114][115][116][117][118] .…”

Section: Discussionmentioning

confidence: 99%

Matrix-GLA-Protein and Vascular Calcification: Can Diet Influence the Consequences of Matrix GLA Protein Inactivation? A Review

Mirzaie

Kusnirova

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et al. 2021

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In vascular calcification, as a physiological process, intimal arterial calcification (IAC) associated with increased cardiovascular risk is distinguished from medial arterial calcification (MAC) localized mainly in the lamina elatica interna, which are not only based on different pathophysiological mechanisms. They also lead to different cardiovascular diseases. While intimal arterial calcification involves inflammation and lipid accumulation, a calcification process similar to desmal ossification plays the main role in medial arterial calcification. In this context, the phenotype change of smooth muscle cells from muscular type to synthesizing form in the tunica media is considered to be of great importance, which puts the matrix GLA protein, mainly involved in bone metabolism, in the center of interest. The present review work elucidates the molecular biological basis of interaction of matrix GLA protein subunits in the pathogenesis of vascular calcifications and the influence of diet on the consequences of underactivation of matrix GLA protein.

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“…Clinical trials are currently ongoing to evaluate the potential efficacy of vitamin K in preventing vascular calcification in hemodialysis patients (iPACK-HD, TReVasc-HDK) [ 118 , 119 ] and in subjects with coronary heart disease (VitaK-CAC) [ 120 ]. Moreover, the AVADEC and BASIK2 randomized trials are investigating the effects of vitamin K2 on the progression of AV calcification [ 121 , 122 ]. These trials are described in detail in Table 2 .…”

Section: Nutraceuticals For Cardiovascular Calcificationmentioning

confidence: 99%

The Emerging Role of Nutraceuticals in Cardiovascular Calcification: Evidence from Preclinical and Clinical Studies

et al. 2021

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Cardiovascular calcification is the ectopic deposition of calcium-phosphate crystals within the arterial wall and the aortic valve leaflets. This pathological process leads to increased vascular stiffness, reduced arterial elasticity, and aortic valve stenosis, increasing the risk of cardiovascular diseases. Although cardiovascular calcification is an increasing health care burden, to date no medical therapies have been approved for treating or preventing it. Considering the current lack of therapeutic strategies and the increasing prevalence of cardiovascular calcification, the investigation of some nutraceuticals to prevent this pathological condition has become prevalent in recent years. Recent preclinical and clinical studies evaluated the potential anti-calcific role of nutraceuticals (including magnesium, zinc, iron, vitamin K, and phytate) in the progression of vascular calcification, providing evidence for their dietary supplementation, especially in high-risk populations. The present review summarizes the current knowledge and latest advances for nutraceuticals with the most relevant preclinical and clinical data, including magnesium, zinc, iron, vitamin K, and phytate. Their supplementation might be recommended as a cost-effective strategy to avoid nutritional deficiency and to prevent or treat cardiovascular calcification. However, the optimal dose of nutraceuticals has not been identified and large interventional trials are warranted to support their protective effects on cardiovascular disease.

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Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial

Cited by 19 publications

References 37 publications

Extent of arterial calcification by conventional vitamin K antagonist treatment

Extent of arterial calcification by conventional vitamin K antagonist treatment

Matrix-GLA-Protein and Vascular Calcification: Can Diet Influence the Consequences of Matrix GLA Protein Inactivation? A Review

The Emerging Role of Nutraceuticals in Cardiovascular Calcification: Evidence from Preclinical and Clinical Studies

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