Skip to main content
Top
Published in: Immunity & Ageing 1/2016

Open Access 01-12-2016 | Research

Frailty has a stronger association with inflammation than age in older veterans

Authors: P. Van Epps, D. Oswald, P. A. Higgins, T. R. Hornick, H. Aung, R. E. Banks, B. M. Wilson, C. Burant, S. Gravenstein, D. H. Canaday

Published in: Immunity & Ageing | Issue 1/2016

Login to get access

Abstract

Background

Upregulation of pro-inflammatory cytokines has not only been associated with increased morbidity and mortality in older adults but also has been linked to frailty. In the current study we aimed to compare the relative relationship of age and frailty on inflammation and thrombosis in older veterans.

Results

We analyzed 117 subjects (age range 62–95 years; median 81) divided into 3 cohorts: non-frail, pre-frail and frail based on the Fried phenotype of frailty. Serum inflammatory markers were determined using commercially available ELISA kits. Frail and pre-frail (PF) subjects had higher levels than non-frail (NF) subjects of IL-6 (NF vs. PF: p = 0.002; NF vs. F: p < 0.001), TNFR1 (NF vs. F: p = 0.012), TNFRII (NF vs. F: 0.002; NF vs. PF: p = 0.005) and inflammatory index: = 0.333*log(IL-6) + 0.666*log(sTNFR1) (NF vs. F: p = 0.009; NF vs. PF: p < 0.001). Frailty status explained a greater percent of variability in markers of inflammation than age: IL-6 (12 % vs. 0.3 %), TNFR1 (5 % vs. 4 %), TNFR2 (11 % vs. 6 %), inflammatory index (16 % vs. 8 %). Aging was significantly associated with higher fibrinogen (p = 0.04) and D-dimer levels (p = 0.01) but only among NF subjects.

Conclusion

In conclusion, these data suggest that among older veterans, frailty status has a stronger association with inflammation and the inflammatory index than age does. Larger studies, in more diverse populations are needed to confirm these findings.
Literature
1.
go back to reference Michaud M, Balardy L, Moulis G, Gaudin C, Peyrot C, Vellas B, Cesari M, Nourhashemi F. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013;14:877–82.CrossRefPubMed Michaud M, Balardy L, Moulis G, Gaudin C, Peyrot C, Vellas B, Cesari M, Nourhashemi F. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013;14:877–82.CrossRefPubMed
2.
go back to reference Baptista G, Dupuy AM, Jaussent A, Durant R, Ventura E, Sauguet P, Picot MC, Jeandel C, Cristol JP. Low-grade chronic inflammation and superoxide anion production by NADPH oxidase are the main determinants of physical frailty in older adults. Free Radic Res. 2012;46:1108–14.CrossRefPubMed Baptista G, Dupuy AM, Jaussent A, Durant R, Ventura E, Sauguet P, Picot MC, Jeandel C, Cristol JP. Low-grade chronic inflammation and superoxide anion production by NADPH oxidase are the main determinants of physical frailty in older adults. Free Radic Res. 2012;46:1108–14.CrossRefPubMed
3.
go back to reference Schlaudecker J, Becker R. Inflammatory response and thrombosis in older individuals. Semin Thromb Hemost. 2014;40:669–74.CrossRefPubMed Schlaudecker J, Becker R. Inflammatory response and thrombosis in older individuals. Semin Thromb Hemost. 2014;40:669–74.CrossRefPubMed
4.
go back to reference Cohen HJ, Harris T, Pieper CF. Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly. Am J Med. 2003;114:180–7.CrossRefPubMed Cohen HJ, Harris T, Pieper CF. Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly. Am J Med. 2003;114:180–7.CrossRefPubMed
5.
go back to reference Deguchi K, Deguchi A, Wada H, Murashima S. Study of cardiovascular risk factors and hemostatic molecular markers in elderly persons. Semin Thromb Hemost. 2000;26:23–7.CrossRefPubMed Deguchi K, Deguchi A, Wada H, Murashima S. Study of cardiovascular risk factors and hemostatic molecular markers in elderly persons. Semin Thromb Hemost. 2000;26:23–7.CrossRefPubMed
6.
go back to reference Scarabin PY, Aillaud MF, Amouyel P, Evans A, Luc G, Ferrieres J, Arveiler D, Juhan-Vague I. Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction--the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction. Thromb Haemost. 1998;80:749–56.PubMed Scarabin PY, Aillaud MF, Amouyel P, Evans A, Luc G, Ferrieres J, Arveiler D, Juhan-Vague I. Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction--the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction. Thromb Haemost. 1998;80:749–56.PubMed
7.
go back to reference Pieper CF, Rao KM, Currie MS, Harris TB, Cohen HJ. Age, functional status, and racial differences in plasma D-dimer levels in community-dwelling elderly persons. J Gerontol A Biol Sci Med Sci. 2000;55:M649–657.CrossRefPubMed Pieper CF, Rao KM, Currie MS, Harris TB, Cohen HJ. Age, functional status, and racial differences in plasma D-dimer levels in community-dwelling elderly persons. J Gerontol A Biol Sci Med Sci. 2000;55:M649–657.CrossRefPubMed
8.
go back to reference Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.CrossRefPubMed Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.CrossRefPubMed
9.
go back to reference Saum KU, Dieffenbach AK, Jansen EH, Schottker B, Holleczek B, Hauer K, Brenner H. Association between Oxidative Stress and Frailty in an Elderly German Population: Results from the ESTHER Cohort Study. Gerontology. 2015;61:407–15.CrossRefPubMed Saum KU, Dieffenbach AK, Jansen EH, Schottker B, Holleczek B, Hauer K, Brenner H. Association between Oxidative Stress and Frailty in an Elderly German Population: Results from the ESTHER Cohort Study. Gerontology. 2015;61:407–15.CrossRefPubMed
10.
go back to reference Kanapuru B, Ershler WB. Inflammation, coagulation, and the pathway to frailty. Am J Med. 2009;122:605–13.CrossRefPubMed Kanapuru B, Ershler WB. Inflammation, coagulation, and the pathway to frailty. Am J Med. 2009;122:605–13.CrossRefPubMed
11.
go back to reference Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–156.CrossRefPubMed Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–156.CrossRefPubMed
12.
go back to reference Leng SX, Tian X, Matteini A, Li H, Hughes J, Jain A, Walston JD, Fedarko NS. IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults. Age Ageing. 2011;40:475–81.CrossRefPubMedPubMedCentral Leng SX, Tian X, Matteini A, Li H, Hughes J, Jain A, Walston JD, Fedarko NS. IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults. Age Ageing. 2011;40:475–81.CrossRefPubMedPubMedCentral
13.
go back to reference Verghese J, Holtzer R, Oh-Park M, Derby CA, Lipton RB, Wang C. Inflammatory markers and gait speed decline in older adults. J Gerontol A Biol Sci Med Sci. 2011;66:1083–9.CrossRefPubMed Verghese J, Holtzer R, Oh-Park M, Derby CA, Lipton RB, Wang C. Inflammatory markers and gait speed decline in older adults. J Gerontol A Biol Sci Med Sci. 2011;66:1083–9.CrossRefPubMed
14.
go back to reference de Gonzalo-Calvo D, de Luxan-Delgado B, Rodriguez-Gonzalez S, Garcia-Macia M, Suarez FM, Solano JJ, Rodriguez-Colunga MJ, Coto-Montes A. Interleukin 6, soluble tumor necrosis factor receptor I and red blood cell distribution width as biological markers of functional dependence in an elderly population: a translational approach. Cytokine. 2012;58:193–8.CrossRefPubMed de Gonzalo-Calvo D, de Luxan-Delgado B, Rodriguez-Gonzalez S, Garcia-Macia M, Suarez FM, Solano JJ, Rodriguez-Colunga MJ, Coto-Montes A. Interleukin 6, soluble tumor necrosis factor receptor I and red blood cell distribution width as biological markers of functional dependence in an elderly population: a translational approach. Cytokine. 2012;58:193–8.CrossRefPubMed
15.
go back to reference McDermott MM, Greenland P, Green D, Guralnik JM, Criqui MH, Liu K, Chan C, Pearce WH, Taylor L, Ridker PM, et al. D-dimer, inflammatory markers, and lower extremity functioning in patients with and without peripheral arterial disease. Circulation. 2003;107:3191–8.CrossRefPubMed McDermott MM, Greenland P, Green D, Guralnik JM, Criqui MH, Liu K, Chan C, Pearce WH, Taylor L, Ridker PM, et al. D-dimer, inflammatory markers, and lower extremity functioning in patients with and without peripheral arterial disease. Circulation. 2003;107:3191–8.CrossRefPubMed
16.
go back to reference McDermott MM, Liu K, Guralnik JM, Ferrucci L, Green D, Greenland P, Tian L, Criqui MH, Lo C, Rifai N, et al. Functional decline in patients with and without peripheral arterial disease: predictive value of annual changes in levels of C-reactive protein and D-dimer. J Gerontol A Biol Sci Med Sci. 2006;61:374–9.CrossRefPubMed McDermott MM, Liu K, Guralnik JM, Ferrucci L, Green D, Greenland P, Tian L, Criqui MH, Lo C, Rifai N, et al. Functional decline in patients with and without peripheral arterial disease: predictive value of annual changes in levels of C-reactive protein and D-dimer. J Gerontol A Biol Sci Med Sci. 2006;61:374–9.CrossRefPubMed
17.
go back to reference Watson DJ, Rhodes T, Cai B, Guess HA. Lower risk of thromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Arch Intern Med. 2002;162:1105–10.CrossRefPubMed Watson DJ, Rhodes T, Cai B, Guess HA. Lower risk of thromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Arch Intern Med. 2002;162:1105–10.CrossRefPubMed
18.
go back to reference Folsom AR, Boland LL, Cushman M, Heckbert SR, Rosamond WD, Walston JD. Frailty and risk of venous thromboembolism in older adults. J Gerontol A Biol Sci Med Sci. 2007;62:79–82.CrossRefPubMed Folsom AR, Boland LL, Cushman M, Heckbert SR, Rosamond WD, Walston JD. Frailty and risk of venous thromboembolism in older adults. J Gerontol A Biol Sci Med Sci. 2007;62:79–82.CrossRefPubMed
19.
go back to reference Varadhan R, Yao W, Matteini A, Beamer BA, Xue QL, Yang H, Manwani B, Reiner A, Jenny N, Parekh N, et al. Simple biologically informed inflammatory index of two serum cytokines predicts 10 year all-cause mortality in older adults. J Gerontol A Biol Sci Med Sci. 2014;69:165–73.CrossRefPubMed Varadhan R, Yao W, Matteini A, Beamer BA, Xue QL, Yang H, Manwani B, Reiner A, Jenny N, Parekh N, et al. Simple biologically informed inflammatory index of two serum cytokines predicts 10 year all-cause mortality in older adults. J Gerontol A Biol Sci Med Sci. 2014;69:165–73.CrossRefPubMed
20.
go back to reference Orme JG, Reis J, Herz EJ. Factorial and discriminant validity of the Center for Epidemiological Studies Depression (CES-D) scale. J Clin Psychol. 1986;42:28–33.CrossRefPubMed Orme JG, Reis J, Herz EJ. Factorial and discriminant validity of the Center for Epidemiological Studies Depression (CES-D) scale. J Clin Psychol. 1986;42:28–33.CrossRefPubMed
21.
go back to reference Taylor HL, Jacobs Jr DR, Schucker B, Knudsen J, Leon AS, Debacker G. A questionnaire for the assessment of leisure time physical activities. J Chronic Dis. 1978;31:741–55.CrossRefPubMed Taylor HL, Jacobs Jr DR, Schucker B, Knudsen J, Leon AS, Debacker G. A questionnaire for the assessment of leisure time physical activities. J Chronic Dis. 1978;31:741–55.CrossRefPubMed
22.
go back to reference Maindonald JH, Braun J. Data analysis and graphics using R : an example-based approach. 2nd ed. Cambridge; New York: Cambridge University Press; 2007. Maindonald JH, Braun J. Data analysis and graphics using R : an example-based approach. 2nd ed. Cambridge; New York: Cambridge University Press; 2007.
23.
go back to reference Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, Saunders LD, Beck CA, Feasby TE, Ghali WA. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43:1130–9.CrossRefPubMed Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, Saunders LD, Beck CA, Feasby TE, Ghali WA. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43:1130–9.CrossRefPubMed
24.
go back to reference de Gonzalo-Calvo D, Fernandez-Garcia B, de Luxan-Delgado B, Rodriguez-Gonzalez S, Garcia-Macia M, Suarez FM, Solano JJ, Rodriguez-Colunga MJ, Coto-Montes A. Long-term training induces a healthy inflammatory and endocrine emergent biomarker profile in elderly men. Age (Dordr). 2012;34:761–71.CrossRef de Gonzalo-Calvo D, Fernandez-Garcia B, de Luxan-Delgado B, Rodriguez-Gonzalez S, Garcia-Macia M, Suarez FM, Solano JJ, Rodriguez-Colunga MJ, Coto-Montes A. Long-term training induces a healthy inflammatory and endocrine emergent biomarker profile in elderly men. Age (Dordr). 2012;34:761–71.CrossRef
25.
go back to reference Ershler WB, Keller ET. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med. 2000;51:245–70.CrossRefPubMed Ershler WB, Keller ET. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med. 2000;51:245–70.CrossRefPubMed
26.
go back to reference Piggott DA, Varadhan R, Mehta SH, Brown TT, Li H, Walston JD, Leng SX, Kirk GD. Frailty, Inflammation, and Mortality Among Persons Aging With HIV Infection and Injection Drug Use. J Gerontol A Biol Sci Med Sci. 2015;70:1542–7.CrossRefPubMedPubMedCentral Piggott DA, Varadhan R, Mehta SH, Brown TT, Li H, Walston JD, Leng SX, Kirk GD. Frailty, Inflammation, and Mortality Among Persons Aging With HIV Infection and Injection Drug Use. J Gerontol A Biol Sci Med Sci. 2015;70:1542–7.CrossRefPubMedPubMedCentral
27.
28.
29.
go back to reference Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH, Gottdiener J, Fried LP, Cardiovascular Health S. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med. 2002;162:2333–41.CrossRefPubMed Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH, Gottdiener J, Fried LP, Cardiovascular Health S. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med. 2002;162:2333–41.CrossRefPubMed
30.
go back to reference Hwang AC, Liu LK, Lee WJ, Chen LY, Peng LN, Lin MH, Chen LK. Association of Frailty and Cardiometabolic Risk Among Community-Dwelling Middle-Aged and Older People: Results from the I-Lan Longitudinal Aging Study. Rejuvenation Res. 2015;18:564–72.CrossRefPubMed Hwang AC, Liu LK, Lee WJ, Chen LY, Peng LN, Lin MH, Chen LK. Association of Frailty and Cardiometabolic Risk Among Community-Dwelling Middle-Aged and Older People: Results from the I-Lan Longitudinal Aging Study. Rejuvenation Res. 2015;18:564–72.CrossRefPubMed
31.
go back to reference Miwa K, Okazaki S, Sakaguchi M, Mochizuki H, Kitagawa K. Interleukin-6, interleukin-6 receptor gene variant, small-vessel disease and incident dementia. Eur J Neurol. 2016;23:656–63.CrossRefPubMed Miwa K, Okazaki S, Sakaguchi M, Mochizuki H, Kitagawa K. Interleukin-6, interleukin-6 receptor gene variant, small-vessel disease and incident dementia. Eur J Neurol. 2016;23:656–63.CrossRefPubMed
32.
go back to reference De Martinis M, Franceschi C, Monti D, Ginaldi L. Inflammation markers predicting frailty and mortality in the elderly. Exp Mol Pathol. 2006;80:219–27.CrossRefPubMed De Martinis M, Franceschi C, Monti D, Ginaldi L. Inflammation markers predicting frailty and mortality in the elderly. Exp Mol Pathol. 2006;80:219–27.CrossRefPubMed
33.
go back to reference Mathei C, Vaes B, Wallemacq P, Degryse J. Associations between cytomegalovirus infection and functional impairment and frailty in the BELFRAIL Cohort. J Am Geriatr Soc. 2011;59:2201–8.CrossRefPubMed Mathei C, Vaes B, Wallemacq P, Degryse J. Associations between cytomegalovirus infection and functional impairment and frailty in the BELFRAIL Cohort. J Am Geriatr Soc. 2011;59:2201–8.CrossRefPubMed
34.
go back to reference Liu CK, Lyass A, Larson MG, Massaro JM, Wang N, D'Agostino Sr RB, Benjamin EJ, Murabito JM. Biomarkers of oxidative stress are associated with frailty: the Framingham Offspring Study. Age (Dordr). 2016;38:1.CrossRef Liu CK, Lyass A, Larson MG, Massaro JM, Wang N, D'Agostino Sr RB, Benjamin EJ, Murabito JM. Biomarkers of oxidative stress are associated with frailty: the Framingham Offspring Study. Age (Dordr). 2016;38:1.CrossRef
35.
go back to reference McDermott MM, Ferrucci L, Liu K, Criqui MH, Greenland P, Green D, Guralnik JM, Ridker PM, Taylor LM, Rifai N, et al. D-dimer and inflammatory markers as predictors of functional decline in men and women with and without peripheral arterial disease. J Am Geriatr Soc. 2005;53:1688–96.CrossRefPubMed McDermott MM, Ferrucci L, Liu K, Criqui MH, Greenland P, Green D, Guralnik JM, Ridker PM, Taylor LM, Rifai N, et al. D-dimer and inflammatory markers as predictors of functional decline in men and women with and without peripheral arterial disease. J Am Geriatr Soc. 2005;53:1688–96.CrossRefPubMed
Metadata
Title
Frailty has a stronger association with inflammation than age in older veterans
Authors
P. Van Epps
D. Oswald
P. A. Higgins
T. R. Hornick
H. Aung
R. E. Banks
B. M. Wilson
C. Burant
S. Gravenstein
D. H. Canaday
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2016
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/s12979-016-0082-z

Other articles of this Issue 1/2016

Immunity & Ageing 1/2016 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.