title: Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury: Framingham Heart Study.
abstract: OBJECTIVE
  Exhaled carbon monoxide (CO) is associated with cardiometabolic traits, subclinical atherosclerosis, and cardiovascular disease, but its specific relations with stroke are unexplored. We related exhaled CO to magnetic resonance imaging measures of subclinical cerebrovascular disease cross-sectionally and to incident stroke/transient ischemic attack prospectively in the Framingham Offspring study.
  
  
  METHODS
  We measured exhaled CO in 3313 participants (age 59±10 years; 53% women), and brain magnetic resonance imaging was available in 1982 individuals (age 58±10 years; 54% women). Participants were analyzed according to tertiles of exhaled CO concentration.
  
  
  RESULTS
  In age- and sex-adjusted models, the highest tertile of exhaled CO was associated with lower total cerebral brain volumes, higher white-matter hyperintensity volumes, and greater prevalence of silent cerebral infarcts (P<0.05 for all). The results for total cerebral brain volume and white-matter hyperintensity volume were consistent after removing smokers from the sample, and the association with white-matter hyperintensity volume persisted after multivariable adjustment (P=0.04). In prospective analyses (mean follow-up 12.9 years), higher exhaled CO was associated with 67% (second tertile) and 97% (top tertile) increased incidence of stroke/transient ischemic attack relative to the first tertile that served as referent (P<0.01 for both). These results were consistent in nonsmokers and were partially attenuated upon adjustment for vascular risk factors.
  
  
  CONCLUSIONS
  In this large, community-based sample of individuals without clinical stroke/transient ischemic attack at baseline, higher exhaled CO was associated with a greater burden of subclinical cerebrovascular disease cross-sectionally and with increased risk of stroke/transient ischemic attack prospectively. Further investigation is necessary to explore the biological mechanisms linking elevated CO with stroke.
authors.affiliation: From the Framingham Heart Study, MA (M.N., A.S.B., S.C., R.S.V., S.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (M.N., S.C.); Departments of Biostatistics (D.M.E., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (A.S.B., S.S) and Sections of Preventive Medicine & Epidemiology and Cardiology, Department of Medicine (R.S.V.), Boston University School of Medicine, MA; and Department of Neurology and Center for Neuroscience, University of California at Davis (C.D.).
authors.forename: Matthew
authors.initials: M
authors.lastname: Nayor
authors.affiliation: From the Framingham Heart Study, MA (M.N., A.S.B., S.C., R.S.V., S.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (M.N., S.C.); Departments of Biostatistics (D.M.E., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (A.S.B., S.S) and Sections of Preventive Medicine & Epidemiology and Cardiology, Department of Medicine (R.S.V.), Boston University School of Medicine, MA; and Department of Neurology and Center for Neuroscience, University of California at Davis (C.D.).
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Enserro
authors.affiliation: From the Framingham Heart Study, MA (M.N., A.S.B., S.C., R.S.V., S.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (M.N., S.C.); Departments of Biostatistics (D.M.E., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (A.S.B., S.S) and Sections of Preventive Medicine & Epidemiology and Cardiology, Department of Medicine (R.S.V.), Boston University School of Medicine, MA; and Department of Neurology and Center for Neuroscience, University of California at Davis (C.D.).
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.affiliation: From the Framingham Heart Study, MA (M.N., A.S.B., S.C., R.S.V., S.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (M.N., S.C.); Departments of Biostatistics (D.M.E., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (A.S.B., S.S) and Sections of Preventive Medicine & Epidemiology and Cardiology, Department of Medicine (R.S.V.), Boston University School of Medicine, MA; and Department of Neurology and Center for Neuroscience, University of California at Davis (C.D.).
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.affiliation: From the Framingham Heart Study, MA (M.N., A.S.B., S.C., R.S.V., S.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (M.N., S.C.); Departments of Biostatistics (D.M.E., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (A.S.B., S.S) and Sections of Preventive Medicine & Epidemiology and Cardiology, Department of Medicine (R.S.V.), Boston University School of Medicine, MA; and Department of Neurology and Center for Neuroscience, University of California at Davis (C.D.).
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: From the Framingham Heart Study, MA (M.N., A.S.B., S.C., R.S.V., S.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (M.N., S.C.); Departments of Biostatistics (D.M.E., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (A.S.B., S.S) and Sections of Preventive Medicine & Epidemiology and Cardiology, Department of Medicine (R.S.V.), Boston University School of Medicine, MA; and Department of Neurology and Center for Neuroscience, University of California at Davis (C.D.).
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: From the Framingham Heart Study, MA (M.N., A.S.B., S.C., R.S.V., S.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (M.N., S.C.); Departments of Biostatistics (D.M.E., A.S.B.) and Epidemiology (R.S.V.), Boston University School of Public Health, MA; Department of Neurology (A.S.B., S.S) and Sections of Preventive Medicine & Epidemiology and Cardiology, Department of Medicine (R.S.V.), Boston University School of Medicine, MA; and Department of Neurology and Center for Neuroscience, University of California at Davis (C.D.).
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases; D050197:Atherosclerosis / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000473:pathology*; D001944:Breath Tests; D002248:Carbon Monoxide / Q000032:analysis / Q000378:metabolism*; D002544:Cerebral Infarction / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology; D066127:White Matter / Q000473:pathology
chemical_list: D002248:Carbon Monoxide
keywords: biomarkers; carbon monoxide; heme oxygenase (decyclizing); ischemic attack, transient; stroke