Associations Between Inflammation and Physical Function in African Americans and European Americans with Prevalent Cardiovascular Risk Factors

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 (cm3) 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.