title: Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans.
abstract: Vascular calcification is a marker of increased cardiovascular risk. Vitamin K-dependent matrix Gla protein (MGP) is important in inhibiting calcification. Because MGP activation is vitamin K dependent, we performed a cross-sectional study investigating the relationship between the use of vitamin K antagonists and extracoronary vascular calcification. From the Dutch thrombosis services we selected 19 patients younger than 55 years who had no other cardiovascular risk factors and who had used coumarins for more than 10 years, and compared these to 18 matched healthy controls. MGP was measured, and a plain x-ray of the thighs was taken to assess femoral arterial calcifications. The odds ratio for calcification in patients versus controls was 8.5 (95% confidence interval [CI] 2.01-35.95). Coumarin use and MGP were associated with calcification, even after adjusting for other risk factors. We conclude that long-term use of coumarins is associated with enhanced extracoronary vascular calcification, possibly through the inhibition of MGP carboxylation.
authors.affiliation: Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands. rennen007@gmail.com
authors.forename: Roger J M W
authors.initials: RJ
authors.lastname: Rennenberg
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: van Varik
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Schurgers
authors.forename: Karly
authors.initials: K
authors.lastname: Hamulyak
authors.forename: Hugo
authors.initials: H
authors.lastname: Ten Cate
authors.forename: Tim
authors.initials: T
authors.lastname: Leiner
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Kroon
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D002114:Calcinosis / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology; D003374:Coumarins / Q000008:administration & dosage / Q000009:adverse effects*; D016208:Databases, Factual; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011859:Radiography; D012044:Regression Analysis; D012307:Risk Factors; D013927:Thrombosis / Q000188:drug therapy* / Q000453:epidemiology; D000097568:Matrix Gla Protein
chemical_list: D000925:Anticoagulants; D002135:Calcium-Binding Proteins; D003374:Coumarins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein; C030123:coumarin