Associations of Mid-to-late-life Inflammation with Late-life Mobility and the Influences of Chronic Comorbidities, Race, and Social Determinants of Health: The Atherosclerosis Risk in Communities Study

Overview

Journal J Am Geriatr Soc

Specialty Geriatrics

Date 2024 Jun 12

PMID 38863338

Authors

Kirby G Parker

B Gwen Windham

Chad Blackshear

Keenan A Walker

Sara B Parker

Ron C Hoogeveen

Christie M Ballantyne

Anna Kucharska-Newton

Priya Palta

Elizabeth Selvin

Maria Vassilaki

Thomas H Mosley

Michael E Griswold

Affiliations

Soon will be listed here.

Abstract

Background: Relationships of midlife inflammation with late-life mobility and influences of chronic health conditions, race, and social determinants of health (SDoH) on these relationships are poorly understood.

Methods: Among 4758 community-dwelling participants (41% men, 20% Black), high-sensitivity C-reactive protein (hsCRP) was measured over 20+ years: in midlife at study visit 2 (V2: 1990-1992, 47-68 years); at V4 (1996-1998, 53-74 years); and with concurrent late-life 4-m gait speed at V5 (2011-2013, 67-88 years, mean 75 years). SDoH measures included race, the national-rank area deprivation index, education, and income. We examined associations of late-life gait speed with midlife hsCRP (V2 continuous and clinically high ≥3 mg/L), with 20-year hsCRP history from midlife (V2-V5 average continuous hsCRP and clinically high ≥3 mg/L) and with inflammation accumulation (visits and years with high hsCRP). Regression models adjusted for demographic, cardiovascular, and SDoH measures; effect modification by the presence of other common chronic conditions (obesity, diabetes, hypertension) and race were examined, with and without accounting for SDoH.

Results: High midlife hsCRP was associated with slower late-life gait speed, even among those without chronic conditions in midlife: -4.6 cm/s (95% CI: -6.4, -2.8). Importantly, sustained high hsCRP was associated with a 20-year slowing of -10.0 cm/s (-14.9, -5.1) among those who never experienced obesity, diabetes, or hypertension over the 20-year period. Associations were similar between Black participants, -3.8 cm/s (-6.9, -0.7) and White participants -3.3 (-4.5, -2.2) per interquartile range of midlife hsCRP; effect modifications by chronic conditions and race were unsupported throughout. Results were robust to accounting for SDoH or otherwise; however, worse SDoH was associated with higher inflammation and slower gait speed in both Black and White participants.

Conclusions: Inflammation in midlife may contribute to clinically meaningful late-life slowing of gait speed, even among otherwise healthy-appearing adults and regardless of race and socioeconomic disadvantage. Regular monitoring and interventions for inflammation may be warranted from midlife.

References

Dupont J, Antonio L, Dedeyne L, ONeill T, Vanderschueren D, Rastrelli G . Inflammatory markers are associated with quality of life, physical activity, and gait speed but not sarcopenia in aged men (40-79 years). J Cachexia Sarcopenia Muscle. 2021; 12(6):1818-1831. PMC: 8718046. DOI: 10.1002/jcsm.12785. View

Rohm T, Meier D, Olefsky J, Donath M . Inflammation in obesity, diabetes, and related disorders. Immunity. 2022; 55(1):31-55. PMC: 8773457. DOI: 10.1016/j.immuni.2021.12.013. View

Bao H, Cao J, Chen M, Chen M, Chen W, Chen X . Biomarkers of aging. Sci China Life Sci. 2023; 66(5):893-1066. PMC: 10115486. DOI: 10.1007/s11427-023-2305-0. View

Nazmi A, Victora C . Socioeconomic and racial/ethnic differentials of C-reactive protein levels: a systematic review of population-based studies. BMC Public Health. 2007; 7:212. PMC: 2018719. DOI: 10.1186/1471-2458-7-212. View

Brinkley T, Leng X, Miller M, Kitzman D, Pahor M, Berry M . Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. J Gerontol A Biol Sci Med Sci. 2009; 64(4):455-61. PMC: 2657165. DOI: 10.1093/gerona/gln038. View

Verghese J, Holtzer R, Oh-Park M, Derby C, Lipton R, Wang C . Inflammatory markers and gait speed decline in older adults. J Gerontol A Biol Sci Med Sci. 2011; 66(10):1083-9. PMC: 3202897. DOI: 10.1093/gerona/glr099. View

Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M . Gait speed and survival in older adults. JAMA. 2011; 305(1):50-8. PMC: 3080184. DOI: 10.1001/jama.2010.1923. View

Cannon J . Cytokines in aging and muscle homeostasis. J Gerontol A Biol Sci Med Sci. 1995; 50 Spec No:120-3. DOI: 10.1093/gerona/50a.special_issue.120. View

Newman J, Milman S, Hashmi S, Austad S, Kirkland J, Halter J . Strategies and Challenges in Clinical Trials Targeting Human Aging. J Gerontol A Biol Sci Med Sci. 2016; 71(11):1424-1434. PMC: 5055653. DOI: 10.1093/gerona/glw149. View

10.

Ferrucci L, Penninx B, Volpato S, Harris T, Bandeen-Roche K, Balfour J . Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels. J Am Geriatr Soc. 2002; 50(12):1947-54. DOI: 10.1046/j.1532-5415.2002.50605.x. View

11.

Tabas I, Glass C . Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science. 2013; 339(6116):166-72. PMC: 3608517. DOI: 10.1126/science.1230720. View

12.

Seals D, Melov S . Translational geroscience: emphasizing function to achieve optimal longevity. Aging (Albany NY). 2014; 6(9):718-30. PMC: 4221919. DOI: 10.18632/aging.100694. View

13.

Nadkarni N, Boudreau R, Studenski S, Lopez O, Liu G, Kritchevsky S . Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults. Neurology. 2016; 87(19):1993-1999. PMC: 5109955. DOI: 10.1212/WNL.0000000000003304. View

14.

Rosamond W, Folsom A, Chambless L, Wang C, McGovern P, Howard G . Stroke incidence and survival among middle-aged adults: 9-year follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort. Stroke. 1999; 30(4):736-43. DOI: 10.1161/01.str.30.4.736. View

15.

Manini T, Anton S, Beavers D, Cauley J, Espeland M, Fielding R . ENabling Reduction of Low-grade Inflammation in SEniors Pilot Study: Concept, Rationale, and Design. J Am Geriatr Soc. 2017; 65(9):1961-1968. PMC: 5642998. DOI: 10.1111/jgs.14965. View

16.

Walker K, Windham B, Power M, Hoogeveen R, Folsom A, Ballantyne C . The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study. Neurobiol Aging. 2018; 68:26-33. PMC: 6010227. DOI: 10.1016/j.neurobiolaging.2018.03.031. View

17.

Cesari M, Penninx B, Pahor M, Lauretani F, Corsi A, Williams G . Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2004; 59(3):242-8. DOI: 10.1093/gerona/59.3.m242. View

18.

Hardy S, Kang Y, Studenski S, Degenholtz H . Ability to walk 1/4 mile predicts subsequent disability, mortality, and health care costs. J Gen Intern Med. 2010; 26(2):130-5. PMC: 3019329. DOI: 10.1007/s11606-010-1543-2. View

19.

Windham B, Wilkening S, Lirette S, Kullo I, Turner S, Griswold M . Associations Between Inflammation and Physical Function in African Americans and European Americans with Prevalent Cardiovascular Risk Factors. J Am Geriatr Soc. 2016; 64(7):1448-55. PMC: 5094054. DOI: 10.1111/jgs.14229. View

20.

Boa Sorte Silva N, Gill D, Gregory M, Bocti J, Petrella R . Multiple-modality exercise and mind-motor training to improve mobility in older adults: A randomized controlled trial. Exp Gerontol. 2017; 103:17-26. DOI: 10.1016/j.exger.2017.12.011. View