title: Circulating vascular cell adhesion molecule-1 is associated with cerebral blood flow dysregulation, mobility impairment, and falls in older adults.
abstract: Soluble vascular cell adhesion molecule-1 (sVCAM-1) is associated with hypertension, vascular inflammation, and systemic endothelial dysfunction. We evaluated whether elevated plasma sVCAM-1 is associated with impaired cerebrovascular function and mobility impairments in elderly people. We studied the cross-sectional relationships between plasma sVCAM-1 level, gait speed, and cerebrovascular hemodynamics, and its longitudinal relationship with falls in 680 community-dwelling participants aged ≥65 years in the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston Study. Falls were recorded prospectively for 1 year on daily calendars. sVCAM-1 was measured by ELISA assay and beat-to-beat blood flow velocity in the middle cerebral artery during rest and in response to changes in end-tidal CO2 was measured by transcranial Doppler ultrasound. sVCAM-1 concentration was 1094±340 ng/mL in normotensives, 1195±438 ng/mL in controlled hypertensives, and 1250±445 ng/mL in uncontrolled hypertensives (P=0.008). The mean resting blood flow velocity and cerebral vasomotor range were, respectively, 41.0±10.3 cm/s and 1.3±0.4 cm/s per millimeter of mercury. Elevated sVCAM-1 levels indicative of endothelial dysfunction were associated with reduced resting blood flow velocity (P=0.017) and cerebral vasomotor range (P=0.0048). Elevated sVCAM-1 levels were associated with slower gait speed (<0.8 m/s; odds ratio, 3.01; 95% confidence interval, 1.56-5.83; P=0.0011) and an increased odds of injurious falls (odds ratio, 2.4; 95% confidence interval, 1.4-4.2; P=0.0028). An elevated sVCAM-1 level may be a marker of cerebral blood flow dysregulation because of endothelial damage from hypertension. It may also signal the presence of cerebral microvascular disease and its clinical consequences, including slow gait speed and falls.
authors.affiliation: From the Institute for Aging Research, Hebrew SeniorLife, Boston, MA (A.E.T., T.G.T., M.G., L.A.L); Beth Israel Deaconess Medical Center, Boston, MA (A.E.T., T.G.T., L.A.L.); Harvard Medical School, Boston, MA (A.E.T., T.G.T., L.A.L.); Limoges University, Limoges, France (A.E.T., T.D.); IFR 145 GEIST; EA 6310 HAVAE (Disability, Activity, Aging, Autonomy and Environment), Geriatric Medicine Department, CHU Limoges, Limoges, France (A.E.T., T.D.); Brown University School of Public Health, Providence, MA (G.A.W.); and Stroke Division, Department of Neurology, Brigham and Women's Hospital, Boston, MA (F.A.S.).
authors.forename: Achille E
authors.initials: AE
authors.lastname: Tchalla
authors.affiliation: From the Institute for Aging Research, Hebrew SeniorLife, Boston, MA (A.E.T., T.G.T., M.G., L.A.L); Beth Israel Deaconess Medical Center, Boston, MA (A.E.T., T.G.T., L.A.L.); Harvard Medical School, Boston, MA (A.E.T., T.G.T., L.A.L.); Limoges University, Limoges, France (A.E.T., T.D.); IFR 145 GEIST; EA 6310 HAVAE (Disability, Activity, Aging, Autonomy and Environment), Geriatric Medicine Department, CHU Limoges, Limoges, France (A.E.T., T.D.); Brown University School of Public Health, Providence, MA (G.A.W.); and Stroke Division, Department of Neurology, Brigham and Women's Hospital, Boston, MA (F.A.S.).
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wellenius
authors.affiliation: From the Institute for Aging Research, Hebrew SeniorLife, Boston, MA (A.E.T., T.G.T., M.G., L.A.L); Beth Israel Deaconess Medical Center, Boston, MA (A.E.T., T.G.T., L.A.L.); Harvard Medical School, Boston, MA (A.E.T., T.G.T., L.A.L.); Limoges University, Limoges, France (A.E.T., T.D.); IFR 145 GEIST; EA 6310 HAVAE (Disability, Activity, Aging, Autonomy and Environment), Geriatric Medicine Department, CHU Limoges, Limoges, France (A.E.T., T.D.); Brown University School of Public Health, Providence, MA (G.A.W.); and Stroke Division, Department of Neurology, Brigham and Women's Hospital, Boston, MA (F.A.S.).
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.affiliation: From the Institute for Aging Research, Hebrew SeniorLife, Boston, MA (A.E.T., T.G.T., M.G., L.A.L); Beth Israel Deaconess Medical Center, Boston, MA (A.E.T., T.G.T., L.A.L.); Harvard Medical School, Boston, MA (A.E.T., T.G.T., L.A.L.); Limoges University, Limoges, France (A.E.T., T.D.); IFR 145 GEIST; EA 6310 HAVAE (Disability, Activity, Aging, Autonomy and Environment), Geriatric Medicine Department, CHU Limoges, Limoges, France (A.E.T., T.D.); Brown University School of Public Health, Providence, MA (G.A.W.); and Stroke Division, Department of Neurology, Brigham and Women's Hospital, Boston, MA (F.A.S.).
authors.forename: Margaret
authors.initials: M
authors.lastname: Gagnon
authors.affiliation: From the Institute for Aging Research, Hebrew SeniorLife, Boston, MA (A.E.T., T.G.T., M.G., L.A.L); Beth Israel Deaconess Medical Center, Boston, MA (A.E.T., T.G.T., L.A.L.); Harvard Medical School, Boston, MA (A.E.T., T.G.T., L.A.L.); Limoges University, Limoges, France (A.E.T., T.D.); IFR 145 GEIST; EA 6310 HAVAE (Disability, Activity, Aging, Autonomy and Environment), Geriatric Medicine Department, CHU Limoges, Limoges, France (A.E.T., T.D.); Brown University School of Public Health, Providence, MA (G.A.W.); and Stroke Division, Department of Neurology, Brigham and Women's Hospital, Boston, MA (F.A.S.).
authors.forename: Ikechukwu
authors.initials: I
authors.lastname: Iloputaife
authors.affiliation: From the Institute for Aging Research, Hebrew SeniorLife, Boston, MA (A.E.T., T.G.T., M.G., L.A.L); Beth Israel Deaconess Medical Center, Boston, MA (A.E.T., T.G.T., L.A.L.); Harvard Medical School, Boston, MA (A.E.T., T.G.T., L.A.L.); Limoges University, Limoges, France (A.E.T., T.D.); IFR 145 GEIST; EA 6310 HAVAE (Disability, Activity, Aging, Autonomy and Environment), Geriatric Medicine Department, CHU Limoges, Limoges, France (A.E.T., T.D.); Brown University School of Public Health, Providence, MA (G.A.W.); and Stroke Division, Department of Neurology, Brigham and Women's Hospital, Boston, MA (F.A.S.).
authors.forename: Thierry
authors.initials: T
authors.lastname: Dantoine
authors.affiliation: From the Institute for Aging Research, Hebrew SeniorLife, Boston, MA (A.E.T., T.G.T., M.G., L.A.L); Beth Israel Deaconess Medical Center, Boston, MA (A.E.T., T.G.T., L.A.L.); Harvard Medical School, Boston, MA (A.E.T., T.G.T., L.A.L.); Limoges University, Limoges, France (A.E.T., T.D.); IFR 145 GEIST; EA 6310 HAVAE (Disability, Activity, Aging, Autonomy and Environment), Geriatric Medicine Department, CHU Limoges, Limoges, France (A.E.T., T.D.); Brown University School of Public Health, Providence, MA (G.A.W.); and Stroke Division, Department of Neurology, Brigham and Women's Hospital, Boston, MA (F.A.S.).
authors.forename: Farzaneh A
authors.initials: FA
authors.lastname: Sorond
authors.affiliation: From the Institute for Aging Research, Hebrew SeniorLife, Boston, MA (A.E.T., T.G.T., M.G., L.A.L); Beth Israel Deaconess Medical Center, Boston, MA (A.E.T., T.G.T., L.A.L.); Harvard Medical School, Boston, MA (A.E.T., T.G.T., L.A.L.); Limoges University, Limoges, France (A.E.T., T.D.); IFR 145 GEIST; EA 6310 HAVAE (Disability, Activity, Aging, Autonomy and Environment), Geriatric Medicine Department, CHU Limoges, Limoges, France (A.E.T., T.D.); Brown University School of Public Health, Providence, MA (G.A.W.); and Stroke Division, Department of Neurology, Brigham and Women's Hospital, Boston, MA (F.A.S.). Lipsitz@hsl.harvard.edu.
authors.forename: Lewis A
authors.initials: LA
authors.lastname: Lipsitz
mesh_terms: D000058:Accidental Falls / Q000706:statistics & numerical data*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005684:Gait / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D015994:Incidence; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology; D051346:Mobility Limitation; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000502:physiology*; D012307:Risk Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D019010:Vascular Cell Adhesion Molecule-1
keywords: brain infarction; endothelium; gait; hypertension