Elevated IL-6 and CRP levels are associated with incident self-reported major mobility disability: A pooled analysis of older adults with slow gait speed

Authors: BEAVERS, DANIEL - WAKE FOREST SCHOOL OF MEDICINE; KRITCHEVSKY, STEPHEN - WAKE FOREST SCHOOL OF MEDICINE; GILL, THOMAS - YALE SCHOOL OF MEDICINE; AMBROSIUS, WALTER - WAKE FOREST SCHOOL OF MEDICINE; ANTON, STEPHEN - UNIVERSITY OF FLORIDA; FIELDING, ROGER - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; KING, ABBY - STANFORD UNIVERSITY SCHOOL OF MEDICINE; REJESKI, W. JACK - WAKE FOREST UNIVERSITY; LOVATO, LAURA - WAKE FOREST SCHOOL OF MEDICINE; MCDERMOTT, MARY - NORTHWESTERN UNIVERSITY; NEWMAN, ANNE - UNIVERSITY OF PITTSBURGH; PAHOR, MARCO - UNIVERSITY OF FLORIDA; WALKUP, MICHAEL - WAKE FOREST SCHOOL OF MEDICINE; TRACY, RUSSELL - UNIVERSITY OF VERMONT; MANINI, TODD - UNIVERSITY OF FLORIDA

Submitted to: Journals of Gerontology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2021
Publication Date: 4/5/2021
Citation: Beavers, D.P., Kritchevsky, S.B., Gill, T.M., Ambrosius, W.T., Anton, S.D., Fielding, R.A., King, A.C., Rejeski, W., Lovato, L., McDermott, M.M., Newman, A.B., Pahor, M., Walkup, M.P., Tracy, R.P., Manini, T.M. 2021. Elevated IL-6 and CRP levels are associated with incident self-reported major mobility disability: A pooled analysis of older adults with slow gait speed. Journals of Gerontology. https://doi.org/10.1093/gerona/glab093.
DOI: https://doi.org/10.1093/gerona/glab093

Interpretive Summary: Interleukine-6 (IL-6) and C-reactive protein (CRP) are proteins in the blood that are markers of inflammation. IL-6 and CRP are associated with aging-related reductions in physical function. In this study we examined whether looking at IL-6 and CRP in combination was associated with major mobility disability (MMD), defined as the self-reported inability to walk a quarter mile. We examined this in older adults (68 years; 59% female) with slow gait speed (<1.0 m/s). The study combined data from a cohort of community-dwelling high-functioning older adults (Health ABC) with 2 clinical trials of low-functioning adults at risk of MMD (LIFE-P, LIFE). We found higher MMD risk with increasing IL-6 concentration. Elevated CRP was also associated with increased MMD risk. The CRP effect was more pronounced among participants who also had elevated IL-6. These results confirm that high baseline IL-6 and CRP were associated with an increased risk of MMD among older adults with slow gait speed. In people with elevated IL-6, the association between CRP and MMD was stronger.

Technical Abstract: Background: Elevated interleukine-6 (IL-6) and C-reactive protein (CRP) are associated with aging-related reductions in physical function, but little is known about their independent and combined relationships with major mobility disability (MMD), defined as the self-reported inability to walk a quarter mile. Methods: We estimated the absolute and relative effect of elevated baseline IL-6, CRP, and their combination on self-reported MMD risk among older adults (>=68 years; 59% female) with slow gait speed (<1.0 m/s). Participants were MMD-free at baseline. IL-6 and CRP were assessed using a central laboratory. The study combined a cohort of community-dwelling high-functioning older adults (Health ABC) with 2 trials of low-functioning adults at risk of MMD (LIFE-P, LIFE). Analyses utilized Poisson regression for absolute MMD incidence and proportional hazards models for relative risk. Results: We found higher MMD risk per unit increase in log IL-6 (hazard ratio [HR] = 1.26; 95% confidence interval [95% CI] 1.13-1.41). IL-6 meeting predetermined threshold considered to be high (>2.5 pg/mL) was similarly associated with higher risk of MMD (HR = 1.31; 95% CI 1.12-1.54). Elevated CRP (CRP >3.0 mg/L) was also associated with increased MMD risk (HR = 1.38; 95% CI 1.10-1.74). The CRP effect was more pronounced among participants with elevated IL-6 (HR = 1.62; 95% CI 1.12-2.33) compared to lower IL-6 levels (HR = 1.19; 95% CI 0.85-1.66). Conclusions: High baseline IL-6 and CRP were associated with an increased risk of MMD among older adults with slow gait speed. A combined biomarker model suggests CRP was associated with MMD when IL-6 was elevated.