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Observational Study
. 2020 Oct 29;15(10):e0241450.
doi: 10.1371/journal.pone.0241450. eCollection 2020.

Extent of arterial calcification by conventional vitamin K antagonist treatment

Selma Hasific  1 , Kristian Altern Øvrehus  1 , Oke Gerke  2 , Jesper Hallas  3 , Martin Busk  4 , Jess Lambrechtsen  5 , Grazina Urbonaviciene  6 , Niels Peter Rønnow Sand  7 , Jens Steen Nielsen  8   9 , Louise Diederichsen  10 , Kenneth Bruun Pedersen  1 , Rasmus Carter-Storch  5 , Nivethitha Ilangkovan  11 , Hans Mickley  1 , Lars Melholt Rasmussen  12 , Jes Sandal Lindholt  13 , Axel Diederichsen  1
Affiliations
Observational Study

Extent of arterial calcification by conventional vitamin K antagonist treatment

Selma Hasific et al. PLoS One. .

Abstract

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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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Selection of study population.
Fig 2
Fig 2. Treatment duration of VKA and NOAC.
AC, Anticoagulants.
Fig 3
Fig 3
Distribution of coronary artery calcium (CAC) score categories in participants with various durations of VKA treatment according to all subjects (A) and three age groups: (B) age <60 years, (C) age 60–69 years and (D) age ≥70 years. P-values for CAC score category distributions by VKA treatment duration were calculated by chi-square test: A) p<0.001, B) p<0.001, C) p = 0.047 and D) p = 0.064.
See this image and copyright information in PMC

References

    1. Medstat.dk. Sundhedsdatastyrelsen. www.medstat.dk Accessed 08 Dec 2018.
    1. Disease burden and mortality estimates. Cause-specific mortality, 2000–2016. World Health Organization. https://www.who.int/healthinfo/global_burden_disease/estimates/en/ Accessed 29 August 2020
    1. Rennenberg RJ, Schurgers LJ, Kroon AA, Stehouwer CD. Arterial calcifications. J Cell Mol Med 2010. September;14(9):2203–2210. 10.1111/j.1582-4934.2010.01139.x - DOI - PMC - PubMed
    1. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997. March 6;386(6620):78–81. 10.1038/386078a0 - DOI - PubMed
    1. Price PA, Faus SA, Williamson MK. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol 1998. September;18(9):1400–7. 10.1161/01.atv.18.9.1400 - DOI - PubMed

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