Warfarin Treatment Is Associated to Increased Internal Carotid Artery Calcification.

Krista Nuotio,Petri T Kovanen,Heli Silvennoinen,Leena Valanne,Ilari Paakkari,Pia Sorto,Mikko I Mäyränpää,Suvi M Koskinen,Hanna M Heikkilä,Jani Saksi,Lauri Soinne,Jarno Tuimala,Sonja Kasari,Laura Mäkitie,Perttu J Lindsberg,Pirkka Vikatmaa,Petra Ijäs

doi:10.3389/fneur.2021.696244

Abstract

Background: Long-term treatment with the vitamin K antagonist warfarin is widely used for the prevention of venous thrombosis and thromboembolism. However, vitamin K antagonists may promote arterial calcification, a phenomenon that has been previously studied in coronary and peripheral arteries, but not in extracranial carotid arteries. In this observational cohort study, we investigated whether warfarin treatment is associated with calcification of atherosclerotic carotid arteries.Methods: Overall, 500 consecutive patients underwent carotid endarterectomy, 82 of whom had received long-term warfarin therapy. The extent of calcification was assessed with preoperative computed tomography angiography, and both macroscopic morphological grading and microscopic histological examination of each excised carotid plaque were performed after carotid endarterectomy.Results: Compared with non-users, warfarin users had significantly more computed tomography angiography-detectable vascular calcification in the common carotid arteries (odds ratio 2.64, 95% confidence interval 1.51–4.63, P < 0.001) and even more calcification in the internal carotid arteries near the bifurcation (odds ratio 18.27, 95% confidence interval 2.53–2323, P < 0.001). Histological analysis revealed that the intramural calcified area in plaques from warfarin users was significantly larger than in plaques from non-users (95% confidence interval 3.36–13.56, P = 0.0018).Conclusions: Long-lasting warfarin anticoagulation associated with increased calcification of carotid atherosclerotic plaques, particularly in locations known to be the predilection sites of stroke-causing plaques. The clinical significance of this novel finding warrants further investigations.

Highlights

An atherosclerotic lesion in the internal carotid artery is a major cause of cerebral ischemic stroke
We examined the preoperative computed tomography angiography (CTA) results, macroscopic calcification of the dissected carotid specimens, and histopathology of the plaques to determine the potential presence of calcification, and the extent of different types of calcification
Because the duration of warfarin therapy was not significantly associated with the degree of calcification, a dichotomous parameter describing warfarin therapy was used in the statistical analysis: 0 = the patient had never received warfarin therapy and 1 = the patient had received warfarin therapy for any period of time

Summary

Introduction

An atherosclerotic lesion in the internal carotid artery is a major cause of cerebral ischemic stroke. Atrial fibrillation (AF), the most common sustained arrhythmia [6] poses a significant risk for cerebral embolism, which is most effectively prevented by anticoagulants [7,8,9] Both warfarin and modern oral anticoagulants are available and neurologists are frequently deciding on anticoagulation on patients with AF, often with simultaneous large artery atherosclerosis. Vitamin K antagonists may promote arterial calcification, a phenomenon that has been previously studied in coronary and peripheral arteries, but not in extracranial carotid arteries. In this observational cohort study, we investigated whether warfarin treatment is associated with calcification of atherosclerotic carotid arteries

Methods

Results

Conclusion