title: Plasma d-Dimer and Incident Ischemic Stroke and Coronary Heart Disease: The Atherosclerosis Risk in Communities Study.
abstract: OBJECTIVE
  Epidemiological studies have documented that plasma d-dimer, a fibrin degradation product, is a risk marker for coronary heart disease, but there is limited prospective evidence for stroke. Given that thrombosis is a key mechanism for many strokes, we studied whether d-dimer is a risk marker for ischemic stroke incidence in the Atherosclerosis Risk in Communities (ARIC) Study.
  
  
  METHODS
  We measured d-dimer in 11 415 ARIC participants free of stroke and coronary heart disease in 1992 to 1995. We followed them for stroke, stroke subtype, and coronary heart disease events through 2012.
  
  
  RESULTS
  Over a median of 18 years of follow-up, 719 participants had incident strokes (628 ischemic and 91 hemorrhagic). d-dimer was associated positively with risk of total, ischemic, and cardioembolic strokes, with risk elevated primarily for the highest quintile of d-dimer. After adjustment for other cardiovascular risk factors, the hazard ratio for the highest versus lowest quintile of d-dimer was 1.30 (95% confidence interval, 1.02-1.67) for total stroke, 1.33 (95% confidence interval, 1.02-1.73) for ischemic stroke, and 1.79 (95% confidence interval, 1.08-2.95) for cardioembolic stroke. There was no association with hemorrhagic, lacunar, or nonlacunar stroke categories. d-dimer was positively but weakly associated with coronary heart disease incidence.
  
  
  CONCLUSIONS
  A higher basal plasma d-dimer concentration in the general population is a risk marker for ischemic stroke, especially cardioembolic stroke.
authors.affiliation: From the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F., D.A.); Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD (R.F.G.); Department of Epidemiology and Biostatistics, Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson (E.S.); and Department of Neurology and Geriatrics/Gerontology, University of Mississippi Medical Center, Jackson (T.H.M.). folso001@umn.edu.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.affiliation: From the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F., D.A.); Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD (R.F.G.); Department of Epidemiology and Biostatistics, Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson (E.S.); and Department of Neurology and Geriatrics/Gerontology, University of Mississippi Medical Center, Jackson (T.H.M.).
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Gottesman
authors.affiliation: From the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F., D.A.); Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD (R.F.G.); Department of Epidemiology and Biostatistics, Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson (E.S.); and Department of Neurology and Geriatrics/Gerontology, University of Mississippi Medical Center, Jackson (T.H.M.).
authors.forename: Duke
authors.initials: D
authors.lastname: Appiah
authors.affiliation: From the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F., D.A.); Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD (R.F.G.); Department of Epidemiology and Biostatistics, Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson (E.S.); and Department of Neurology and Geriatrics/Gerontology, University of Mississippi Medical Center, Jackson (T.H.M.).
authors.forename: Eyal
authors.initials: E
authors.lastname: Shahar
authors.affiliation: From the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F., D.A.); Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD (R.F.G.); Department of Epidemiology and Biostatistics, Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson (E.S.); and Department of Neurology and Geriatrics/Gerontology, University of Mississippi Medical Center, Jackson (T.H.M.).
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
mesh_terms: D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012111:Residence Characteristics; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D
keywords: coronary disease; epidemiological studies; fibrin fragment D; prospective studies; stroke