B Gwen Windham1, Steven R Wilkening2, Seth T Lirette3, Iftikhar J Kullo4, Stephen T Turner5, Michael E Griswold3, Thomas H Mosley1. 1. Division of Geriatrics, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi. 2. School of Medicine, University of Mississippi Medical Center, Jackson, Mississippi. 3. Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, Mississippi. 4. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. 5. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
Abstract
OBJECTIVES: To examine associations between inflammation and physical function and potential mediation by white matter hyperintensities (WMHs) in African Americans (AAs) and European Americans (EAs). DESIGN: Cross-sectional analysis using linear and logistic models with generalized estimating equations to account for family clustering, reporting results as regression coefficients (β) and odds ratios (ORs) adjusted for education, alcohol, exercise, body mass index, hypertension, diabetes mellitus, heart disease, cognition, ankle-brachial index, race (site), and supported interactions. SETTING: Genetic Epidemiology Network of Arteriopathy-Genetics of Microangiopathic Brain Injury Study cohort. PARTICIPANTS: AA and EA sibships with two or more siblings with hypertension before age 60 (N = 1,960; 65% female, 51% AA, aged 26-91, 50% obese, 72% hypertensive). MEASUREMENTS: Inflammation (C-reactive protein (CRP), interleukin-6 (IL6), soluble tumor necrosis factor receptors (sTNFRs) 1 and 2, WMH volume (cm(3) ) according to magnetic resonance imaging), walking speed (cm/s) over 25 feet, and mobility difficulty (any self-reported difficulty walking half a mile). RESULTS: In separate models, inflammatory markers were associated with walking speed (sTNFR1: β = -2.74, P < .001; sTNFR2: β = -1.23, P = .03; CRP: β = -1.95, P = .001; IL6: β = -1.24, P = .03) and mobility difficulty (sTNFR1: OR = 1.36, P = .001; sTNFR2: OR = 1.25, P = .005; CRP: OR = 1.22, P = .005; IL6: OR = 1.18, P = .02); the association between WMH volume and sTNFR1 in AA (β = 0.07, P = .06) did not reach typical statistical thresholds. WMH volume was associated with walking speed in AA (β = -3.17, P = .02) but not with mobility difficulty (OR = 1.10, P = .54). Adjusting for WMH did not change associations. CONCLUSION: In young, middle-aged, and older adults with prevalent cardiovascular risk factors, multiple inflammatory biomarkers were associated with slower walking speed independent of microvascular disease in the brain. There was little evidence of mediation by brain WMH volume. Inflammation may contribute to physical function impairments through pathways other than brain microvascular disease, particularly in AAs.
OBJECTIVES: To examine associations between inflammation and physical function and potential mediation by white matter hyperintensities (WMHs) in African Americans (AAs) and European Americans (EAs). DESIGN: Cross-sectional analysis using linear and logistic models with generalized estimating equations to account for family clustering, reporting results as regression coefficients (β) and odds ratios (ORs) adjusted for education, alcohol, exercise, body mass index, hypertension, diabetes mellitus, heart disease, cognition, ankle-brachial index, race (site), and supported interactions. SETTING: Genetic Epidemiology Network of Arteriopathy-Genetics of Microangiopathic Brain Injury Study cohort. PARTICIPANTS: AA and EA sibships with two or more siblings with hypertension before age 60 (N = 1,960; 65% female, 51% AA, aged 26-91, 50% obese, 72% hypertensive). MEASUREMENTS: Inflammation (C-reactive protein (CRP), interleukin-6 (IL6), soluble tumor necrosis factor receptors (sTNFRs) 1 and 2, WMH volume (cm(3) ) according to magnetic resonance imaging), walking speed (cm/s) over 25 feet, and mobility difficulty (any self-reported difficulty walking half a mile). RESULTS: In separate models, inflammatory markers were associated with walking speed (sTNFR1: β = -2.74, P < .001; sTNFR2: β = -1.23, P = .03; CRP: β = -1.95, P = .001; IL6: β = -1.24, P = .03) and mobility difficulty (sTNFR1: OR = 1.36, P = .001; sTNFR2: OR = 1.25, P = .005; CRP: OR = 1.22, P = .005; IL6: OR = 1.18, P = .02); the association between WMH volume and sTNFR1 in AA (β = 0.07, P = .06) did not reach typical statistical thresholds. WMH volume was associated with walking speed in AA (β = -3.17, P = .02) but not with mobility difficulty (OR = 1.10, P = .54). Adjusting for WMH did not change associations. CONCLUSION: In young, middle-aged, and older adults with prevalent cardiovascular risk factors, multiple inflammatory biomarkers were associated with slower walking speed independent of microvascular disease in the brain. There was little evidence of mediation by brain WMH volume. Inflammation may contribute to physical function impairments through pathways other than brain microvascular disease, particularly in AAs.
Authors: Linda P Fried; Luigi Ferrucci; Jonathan Darer; Jeff D Williamson; Gerard Anderson Journal: J Gerontol A Biol Sci Med Sci Date: 2004-03 Impact factor: 6.053
Authors: H Baezner; C Blahak; A Poggesi; L Pantoni; D Inzitari; H Chabriat; T Erkinjuntti; F Fazekas; J M Ferro; P Langhorne; J O'Brien; P Scheltens; M C Visser; L O Wahlund; G Waldemar; A Wallin; M G Hennerici Journal: Neurology Date: 2008-03-18 Impact factor: 9.910
Authors: D Aderka; P Sorkine; S Abu-Abid; D Lev; A Setton; A P Cope; D Wallach; J Klausner Journal: J Clin Invest Date: 1998-02-01 Impact factor: 14.808
Authors: Stefano Volpato; Caroline Blaum; Helaine Resnick; Luigi Ferrucci; Linda P Fried; Jack M Guralnik Journal: Diabetes Care Date: 2002-04 Impact factor: 19.112
Authors: Karlijn F de Laat; Anouk G W van Norden; Rob A R Gons; Lucas J B van Oudheusden; Inge W M van Uden; Bastiaan R Bloem; Marcel P Zwiers; Frank-Erik de Leeuw Journal: Stroke Date: 2010-06-24 Impact factor: 7.914
Authors: Esther M Brooks-Asplund; Carrie E Tupper; Jane M Daun; W Larry Kenney; Joseph G Cannon Journal: Cytokine Date: 2002-08-21 Impact factor: 3.861
Authors: Muhammad S Ali; Robert M Starke; Pascal M Jabbour; Stavropoula I Tjoumakaris; L Fernando Gonzalez; Robert H Rosenwasser; Gary K Owens; Walter J Koch; Nigel H Greig; Aaron S Dumont Journal: J Cereb Blood Flow Metab Date: 2013-07-17 Impact factor: 6.200
Authors: Kyoung Shin Park; Alexis B Ganesh; Nathaniel T Berry; Yashonda P Mobley; William B Karper; Jeffrey D Labban; Christopher N Wahlheim; Tomika M Williams; Laurie Wideman; Jennifer L Etnier Journal: BMC Neurol Date: 2020-06-06 Impact factor: 2.474