Jie Ding1, Gary F Mitchell1, Michiel L Bots1, Sigurdur Sigurdsson1, Tamara B Harris1, Melissa Garcia1, Gudny Eiriksdottir1, Mark A van Buchem1, Vilmundur Gudnason1, Lenore J Launer2. 1. 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.). 2. 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.
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. APPROACH AND 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.
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. APPROACH AND 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: Mariëlle M F Poels; Kèren Zaccai; Germaine C Verwoert; Meike W Vernooij; Albert Hofman; Aad van der Lugt; Jacqueline C M Witteman; Monique M B Breteler; Francesco U S Mattace-Raso; M Arfan Ikram Journal: Stroke Date: 2012-08-09 Impact factor: 7.914
Authors: Thomas T van Sloten; Miranda T Schram; Katja van den Hurk; Jacqueline M Dekker; Giel Nijpels; Ronald M A Henry; Coen D A Stehouwer Journal: J Am Coll Cardiol Date: 2014-02-26 Impact factor: 24.094
Authors: Gary F Mitchell; Helen Parise; Emelia J Benjamin; Martin G Larson; Michelle J Keyes; Joseph A Vita; Ramachandran S Vasan; Daniel Levy Journal: Hypertension Date: 2004-05-03 Impact factor: 10.190
Authors: Alastair J S Webb; Michela Simoni; Sara Mazzucco; Wilhelm Kuker; Ursula Schulz; Peter M Rothwell Journal: Stroke Date: 2012-08-23 Impact factor: 7.914
Authors: Benjamin S Aribisala; Zoe Morris; Elizabeth Eadie; Avril Thomas; Alan Gow; Maria C Valdés Hernández; Natalie A Royle; Mark E Bastin; John Starr; Ian J Deary; Joanna M Wardlaw Journal: Hypertension Date: 2014-01-27 Impact factor: 10.190
Authors: Jessica L Fry; Leona Al Sayah; Robert M Weisbrod; Isabelle Van Roy; Xiang Weng; Richard A Cohen; Markus M Bachschmid; Francesca Seta Journal: Hypertension Date: 2016-07-18 Impact factor: 10.190
Authors: Tatjana Rundek; David Della-Morte; Hannah Gardener; Chuanhui Dong; Matthew S Markert; Jose Gutierrez; Eugene Roberts; Mitchell S V Elkind; Charles DeCarli; Ralph L Sacco; Clinton B Wright Journal: Neurology Date: 2017-04-26 Impact factor: 9.910