Extent of arterial calcification by conventional vitamin K antagonist treatment.

Selma Hasific,Grazina Urbonaviciene,Nivethitha Ilangkovan,Kristian Altern Øvrehus,Jesper Hallas,Axel Diederichsen,Kenneth Bruun Pedersen,Lars Melholt Rasmussen,Rasmus Carter-Storch,Jes Sandal Lindholt,Oke Gerke,Hans Mickley,Louise Diederichsen,Martin Busk,Jens Steen Nielsen,Niels Peter Rønnow Sand,Jess Lambrechtsen

doi:10.1371/journal.pone.0241450

Abstract

Background and aimsVitamin 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).MethodsWe 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.ResultsThe 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.ConclusionsAdjusted for cardiovascular risk factors, VKA treatment–contrary to NOAC—was associated to higher CAC category.

Highlights

Vitamin K antagonists (VKA) have been the most widely prescribed anticoagulants since their introduction in 1954
The final study population consisted of 17,254 participants with no prior cardiovascular disease (CVD), of whom 1,748 and 1,144 had been treated with VKA or non-vitamin K antagonist oral anticoagulants (NOAC), respectively
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Summary

Introduction

Vitamin K antagonists (VKA) have been the most widely prescribed anticoagulants since their introduction in 1954. VKA inhibit the recycling of vitamin K, including phylloquinone (vitamin K1) and menaquinone (vitamin K2) They are essential for activation of functional clotting factors II, VII, IX and X, and γ-carboxylation of proteins involved in inhibition of arterial calcification, i.e. matrix-Gla proteins (MGP), respectively. MGP is a potent local inhibitor produced in the vascular smooth muscle cells in the vessel wall It acts by inhibiting calcium crystal formation and regulating bone morphogenetic protein 2, which is a growth factor responsible for osteogenic differentiation [3]. 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)

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