Warfarin Treatment Is Associated to Increased Internal Carotid Artery Calcification

You'll need your doctor to monitor this. In my case I was only on it for 2 months, later on they say the median duration was 1.6 years, so I guess I was ok.

Warfarin Treatment Is Associated to Increased Internal Carotid Artery Calcification

 

Krista Nuotio^1,2*, Suvi M. Koskinen^2,3, Laura Mäkitie^1,2, Jarno Tuimala⁴, Petra Ijäs^1,2, Hanna M. Heikkilä², Jani Saksi², Pirkka Vikatmaa⁵, Pia Sorto², Sonja Kasari², Ilari Paakkari⁶, Heli Silvennoinen³, Leena Valanne³, Mikko I. Mäyränpää⁷, Lauri Soinne^1,2, Petri T. Kovanen⁸ and Perttu J. Lindsberg^1,2

• ¹Neurology, Neurocenter, Helsinki University Hospital, Helsinki, Finland
• ²Clinical Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland
• ³Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
• ⁴Independent Researcher, Helsinki, Finland
• ⁵Abdominal Center, Vascular Surgery, Helsinki University Hospital, Helsinki, Finland
• ⁶Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
• ⁷Pathology, Helsinki University and Helsinki University Hospital, Helsinki, Finland
• ⁸Wihuri Research Institute, Biomedicum Helsinki 1, Helsinki, Finland

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.

Introduction

An atherosclerotic lesion in the internal carotid artery is a major cause of cerebral ischemic stroke. Although many elements of the underlying pathological processes of atherosclerosis, e.g., lipid accumulation and the inflammatory component, have been well-characterized in developing atherosclerotic lesions (1), the multifaceted roles of calcification in atherosclerotic lesions are still debated and under investigation (2–5).

Atrial fibrillation (AF), the most common sustained arrhythmia (6) poses a significant risk for cerebral embolism, which is most effectively prevented by anticoagulants (7–9). 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.

Warfarin has been claimed to have harmful effects on the arterial wall. Evidence from experimental animals has demonstrated that treatment with warfarin is linked to vascular calcification (10, 11), with similar findings from preliminary human studies (12–14). Human studies have suggested that exposure to warfarin may increase calcification in coronary arteries (15, 16), peripheral arteries (17), aorta (18), and aortic valve leaflets (19).

However, there are only a few studies that have investigated the association of warfarin and vascular calcification in carotid arteries (20, 21), and none of them has studied vascular calcification in extracranial carotid arteries. Hence, the present clinical investigation was undertaken to evaluate the hypothesis that chronic warfarin use is associated with vascular calcification in atherosclerotic carotid artery disease. 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. The results obtained in users and non-users of warfarin therapy were compared.