Warfarin Treatment Is Associated to Increased Internal Carotid Artery Calcification

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.

Regulatory effects of nutritional and metabolic disorders on vascular calcification in chronic kidney disease: a narrative review

“…Warfarin increases calcium deposition in the thoracic and abdominal aortas of uremic rats, which can be ameliorated by high doses of vitamin K2 ( 40 ) ( Table 2 ). Consistent with in vivo studies, clinical studies have shown that warfarin significantly increases the occurrence and progression of VC ( 92 , 93 ). Although a post hoc analysis of the ViKCoVaC (effect of Vitamin-K1 and Colchicine on Vascular Calcification activity in subjects with Diabetes Mellitus) double-blind randomized controlled trial showed that vitamin K1 supplements (10 mg/day) delay the progression of CAC in diabetic patients ( 94 ), clinical evidence for VC delay in CKD patients is scarce.…”

Vitamin K antagonists and cardiovascular calcification: A systematic review and meta-analysis

“…Nine study cohorts were cross-sectional with an unspecified duration of treatment (28,33,43,44,46,47,53,56,58). The medical history of the patients included coronary artery disease (CAD) (27,32,39), chronic kidney disease CKD (including patients with ESRD) (29, 40-43, 46, 47, 53, 55), calcific aortic valve disease or aortic stenosis (CAVD/AS) (28,56,57,60), atrial fibrillation (AF/NVAF) (28,29,32,34,38,39,49,54,55,58,61), metallic prosthetic valves (36), lower limb amputation (44), carotid atherectomy (48), non-traumatic cerebral hemorrhage (50) or underwent cardiac CT (33, 35) or mammography (40, 52) tests for diagnostic or screening purposes. Two studies included the general population from health registries (30,59).…”

Cardiac Calcifications: Phenotypes, Mechanisms, Clinical and Prognostic Implications

“…Several studies have shown that anticoagulant therapy warfarin is associated with increased calcification in various districts, including coronary arteries [89], carotids [90], lower-extremity arteries [91], abdominal aorta, and heart valves [92]. Warfarin is a competitor of vitamin K, and there is evidence that it accelerates calcification by affecting vitamin K-dependent MGP activation, hence, reducing the physiological anti-calcific properties of this protein [93].…”