title: Use of coumarin anticoagulants and cerebral microbleeds in the general population.
abstract: OBJECTIVE
  It remains undetermined whether the use of coumarin anticoagulants associates with cerebral microbleeds in the general population. We investigated whether (1) coumarin use relates to higher prevalence and incidence of microbleeds, (2) microbleeds are more frequent in people with higher maximum international normalized ratios (INRs), and (3) among coumarin users, variability in INR associates with microbleed presence.
  
  
  METHODS
  From the population-based Rotterdam Study, 4945 participants aged ≥45 years were included in the cross-sectional analysis, and 3069 participants had follow-up brain MRI. Information on coumarin use was obtained from automated pharmacy records. Coumarin users were monitored, and INR values were measured in consecutive visits. Presence and location of microbleeds were rated on brain MRI. We investigated the association of coumarin use with microbleeds using multivariable logistic regression.
  
  
  RESULTS
  Overall, 8.6% had used coumarin anticoagulants before the first MRI and 5.9% before follow-up MRI. The prevalence of microbleeds was 19.4%, and the incidence was 6.9% during a mean follow-up of 3.9 years (SD, 0.5). Compared with never users, coumarin users had a higher prevalence of deep or infratentorial microbleeds and a higher incidence of any microbleeds, although statistical significance was not reached in the latter. A higher maximum INR was associated with deep or infratentorial microbleeds. Among coumarin users, a greater variability in INR was associated with a higher prevalence of microbleeds.
  
  
  CONCLUSIONS
  Coumarin use is associated with microbleeds. Associations were strongest for people with greater variability in INR.
authors.affiliation: From the Departments of Epidemiology (S.A., S.K.L.D., M.J.G.L., A.H., B.H.S., M.A.I., M.W.V.), Radiology (S.A., A.v.d.L., M.A.I., M.W.V.), Neurology (S.A., P.J.K., M.A.I.), and Cardiology (M.J.G.L.), Erasmus MC, Rotterdam, the Netherlands; and Inspectorate of Health Care, The Hague, the Netherlands (B.H.S.).
authors.forename: Saloua
authors.initials: S
authors.lastname: Akoudad
authors.affiliation: From the Departments of Epidemiology (S.A., S.K.L.D., M.J.G.L., A.H., B.H.S., M.A.I., M.W.V.), Radiology (S.A., A.v.d.L., M.A.I., M.W.V.), Neurology (S.A., P.J.K., M.A.I.), and Cardiology (M.J.G.L.), Erasmus MC, Rotterdam, the Netherlands; and Inspectorate of Health Care, The Hague, the Netherlands (B.H.S.).
authors.forename: Sirwan K L
authors.initials: SK
authors.lastname: Darweesh
authors.affiliation: From the Departments of Epidemiology (S.A., S.K.L.D., M.J.G.L., A.H., B.H.S., M.A.I., M.W.V.), Radiology (S.A., A.v.d.L., M.A.I., M.W.V.), Neurology (S.A., P.J.K., M.A.I.), and Cardiology (M.J.G.L.), Erasmus MC, Rotterdam, the Netherlands; and Inspectorate of Health Care, The Hague, the Netherlands (B.H.S.).
authors.forename: Maarten J G
authors.initials: MJ
authors.lastname: Leening
authors.affiliation: From the Departments of Epidemiology (S.A., S.K.L.D., M.J.G.L., A.H., B.H.S., M.A.I., M.W.V.), Radiology (S.A., A.v.d.L., M.A.I., M.W.V.), Neurology (S.A., P.J.K., M.A.I.), and Cardiology (M.J.G.L.), Erasmus MC, Rotterdam, the Netherlands; and Inspectorate of Health Care, The Hague, the Netherlands (B.H.S.).
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koudstaal
authors.affiliation: From the Departments of Epidemiology (S.A., S.K.L.D., M.J.G.L., A.H., B.H.S., M.A.I., M.W.V.), Radiology (S.A., A.v.d.L., M.A.I., M.W.V.), Neurology (S.A., P.J.K., M.A.I.), and Cardiology (M.J.G.L.), Erasmus MC, Rotterdam, the Netherlands; and Inspectorate of Health Care, The Hague, the Netherlands (B.H.S.).
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From the Departments of Epidemiology (S.A., S.K.L.D., M.J.G.L., A.H., B.H.S., M.A.I., M.W.V.), Radiology (S.A., A.v.d.L., M.A.I., M.W.V.), Neurology (S.A., P.J.K., M.A.I.), and Cardiology (M.J.G.L.), Erasmus MC, Rotterdam, the Netherlands; and Inspectorate of Health Care, The Hague, the Netherlands (B.H.S.).
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: From the Departments of Epidemiology (S.A., S.K.L.D., M.J.G.L., A.H., B.H.S., M.A.I., M.W.V.), Radiology (S.A., A.v.d.L., M.A.I., M.W.V.), Neurology (S.A., P.J.K., M.A.I.), and Cardiology (M.J.G.L.), Erasmus MC, Rotterdam, the Netherlands; and Inspectorate of Health Care, The Hague, the Netherlands (B.H.S.).
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: From the Departments of Epidemiology (S.A., S.K.L.D., M.J.G.L., A.H., B.H.S., M.A.I., M.W.V.), Radiology (S.A., A.v.d.L., M.A.I., M.W.V.), Neurology (S.A., P.J.K., M.A.I.), and Cardiology (M.J.G.L.), Erasmus MC, Rotterdam, the Netherlands; and Inspectorate of Health Care, The Hague, the Netherlands (B.H.S.).
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: From the Departments of Epidemiology (S.A., S.K.L.D., M.J.G.L., A.H., B.H.S., M.A.I., M.W.V.), Radiology (S.A., A.v.d.L., M.A.I., M.W.V.), Neurology (S.A., P.J.K., M.A.I.), and Cardiology (M.J.G.L.), Erasmus MC, Rotterdam, the Netherlands; and Inspectorate of Health Care, The Hague, the Netherlands (B.H.S.). m.vernooij@erasmusmc.nl.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects*; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D003374:Coumarins / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011159:Population Surveillance / Q000379:methods
chemical_list: D000925:Anticoagulants; D003374:Coumarins; C030123:coumarin
keywords: anticoagulants; cerebral small vessel disease; epidemiology; magnetic resonance imaging