title: Carotid arterial stiffness and risk of incident cerebral microbleeds in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study.
abstract: OBJECTIVE
  Age and high blood pressure are major risk factors for cerebral microbleeds (CMBs). However, the underlying mechanisms remain unclear and arterial stiffness may be important. We investigated whether carotid arterial stiffness is associated with incidence and location of CMBs.
  
  
  RESULTS
  In the prospective, population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik study, 2512 participants aged 66 to 93 years underwent a baseline brain MRI examination and carotid ultrasound in 2002 to 2006 and returned for a repeat brain MRI in 2007 to 2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain, distensibility coefficient, and Young elastic modulus. Modified Poisson regression was applied to relate carotid arterial stiffness parameters to CMB incidence. During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex, and follow-up interval, arterial stiffness measures were associated with incident CMBs (risk ratio per SD decrease in carotid arterial strain, 1.11 [95% confidence interval, 1.01-1.21]; per SD decrease in natural log-transformed distensibility coefficient, 1.14 [1.05-1.24]; and per SD increase in natural log-transformed Young elastic modulus, 1.13 [1.04-1.23]). These measures were also significantly associated with incident deep CMBs (1.18 [1.02-1.37]; 1.24 [1.08-1.42]; and 1.23 [1.07-1.42]) but not with lobar CMBs. When further adjusted for blood pressure and other baseline vascular risk factors, carotid plaque, prevalent CMBs, subcortical infarcts, and white matter hyperintensities, the associations persisted.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially in a deep location attributable to hypertension.
authors.affiliation: From the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD (J.D., T.B.H., M.G., L.J.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Icelandic Heart Association, Kopavogur, Iceland (S.S., G.E., V.G.); Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands (M.A.v.B.); and Faculty of Medicine, University of Iceland, Reykjavik, Iceland (V.G.).
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: From the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD (J.D., T.B.H., M.G., L.J.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Icelandic Heart Association, Kopavogur, Iceland (S.S., G.E., V.G.); Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands (M.A.v.B.); and Faculty of Medicine, University of Iceland, Reykjavik, Iceland (V.G.).
authors.forename: Gary F
authors.initials: GF
authors.lastname: Mitchell
authors.affiliation: From the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD (J.D., T.B.H., M.G., L.J.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Icelandic Heart Association, Kopavogur, Iceland (S.S., G.E., V.G.); Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands (M.A.v.B.); and Faculty of Medicine, University of Iceland, Reykjavik, Iceland (V.G.).
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.affiliation: From the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD (J.D., T.B.H., M.G., L.J.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Icelandic Heart Association, Kopavogur, Iceland (S.S., G.E., V.G.); Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands (M.A.v.B.); and Faculty of Medicine, University of Iceland, Reykjavik, Iceland (V.G.).
authors.forename: Sigurdur
authors.initials: S
authors.lastname: Sigurdsson
authors.affiliation: From the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD (J.D., T.B.H., M.G., L.J.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Icelandic Heart Association, Kopavogur, Iceland (S.S., G.E., V.G.); Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands (M.A.v.B.); and Faculty of Medicine, University of Iceland, Reykjavik, Iceland (V.G.).
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.affiliation: From the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD (J.D., T.B.H., M.G., L.J.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Icelandic Heart Association, Kopavogur, Iceland (S.S., G.E., V.G.); Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands (M.A.v.B.); and Faculty of Medicine, University of Iceland, Reykjavik, Iceland (V.G.).
authors.forename: Melissa
authors.initials: M
authors.lastname: Garcia
authors.affiliation: From the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD (J.D., T.B.H., M.G., L.J.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Icelandic Heart Association, Kopavogur, Iceland (S.S., G.E., V.G.); Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands (M.A.v.B.); and Faculty of Medicine, University of Iceland, Reykjavik, Iceland (V.G.).
authors.forename: Gudny
authors.initials: G
authors.lastname: Eiriksdottir
authors.affiliation: From the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD (J.D., T.B.H., M.G., L.J.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Icelandic Heart Association, Kopavogur, Iceland (S.S., G.E., V.G.); Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands (M.A.v.B.); and Faculty of Medicine, University of Iceland, Reykjavik, Iceland (V.G.).
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: From the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD (J.D., T.B.H., M.G., L.J.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Icelandic Heart Association, Kopavogur, Iceland (S.S., G.E., V.G.); Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands (M.A.v.B.); and Faculty of Medicine, University of Iceland, Reykjavik, Iceland (V.G.).
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.affiliation: From the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD (J.D., T.B.H., M.G., L.J.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Icelandic Heart Association, Kopavogur, Iceland (S.S., G.E., V.G.); Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands (M.A.v.B.); and Faculty of Medicine, University of Iceland, Reykjavik, Iceland (V.G.). LaunerL@nia.nih.gov.
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000473:pathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D055119:Elastic Modulus; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007055:Iceland / Q000453:epidemiology; D015994:Incidence; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D059289:Vascular Stiffness
keywords: carotid arteries; cerebral small vessel diseases; incidence; vascular stiffness