Extent of arterial calcification by conventional vitamin K antagonist treatment

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

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.