1.2 VASCULAR CALCIFICATIONS AFTER CHRONIC USE OF VITAMIN-K ANTAGONISTS

Abstract

Background: Arterial calcification is commonly observed in cardiovascular disease and is associated with increased arterial stiffness, systolic hypertension and adverse cardiovascular outcome. Arterial calcification is an actively regulated process with several stimulating and inhibiting factors. An important inhibitor of arterial calcification is the Vitamin K-dependent Matrix Gla Protein (MGP). In animal studies, inhibition of Vitamin K by warfarin-treatment was associated with increased arterial calcification. We investigated in this pilot-study whether this effect of Vitamin-K antagonists could also be observed in humans. Methods: From five different thrombosis services in the Netherlands, we recruited 19 patients that have used oral vitamin-K antagonists for more than 10 years due to an history of cardiac valve replacement or venous thrombo-embolic event. We also recruited 17 control-subjects. We excluded subjects older than 55 years or subjects with a history of diabetes, hyperhomocysteinemia, hyperlipidemia and previous cardiovascular events. To detect arterial calcification, anterior soft-tissue radiographs from the femoral arteries were obtained in all subjects. In addition, the carotid Intima Media Thickness (cIMT) and carotid-femoral Pulse-wave Velocity (PWV) were measured. Results and conclusion: Femoral radiographs of sufficient quality were obtained for 18 patients and 16 controls. Fourteen (77.8%) patients on vitamin-K antagonists versus 4 (25%) control subjects had femoral artery calcifications (Odds-ratio 10.5; 95%–CI 2.15 – 51.28). Patients had a slightly higher mean cIMT (0.61±0.09mm) than control subjects (0.56±0.07mm; p=0.04).There was no difference in carotid-femoral PWV between the groups. Chronic use of Vitamin-K antagonists is associated with increased arterial calcification.