Skip to main content
Top
Published in: Arthritis Research & Therapy 1/2015

Open Access 01-12-2015 | Research article

Increased carotid artery intima-media thickness and myeloperoxidase level in children with newly diagnosed juvenile idiopathic arthritis

Authors: Jaanika Ilisson, Maksim Zagura, Kersti Zilmer, Erik Salum, Kaire Heilman, Anneli Piir, Vallo Tillmann, Jaak Kals, Mihkel Zilmer, Chris Pruunsild

Published in: Arthritis Research & Therapy | Issue 1/2015

Login to get access

Abstract

Introduction

Juvenile idiopathic arthritis (JIA) is a frequent childhood rheumatic disease characterized by chronic inflammation. The latter has been related to impairment of arterial functional-structural properties, atherogenesis and later cardiovascular events. The objective of this study was to examine intima-media thickness (IMT) and the parameters of arterial stiffness in children with JIA at diagnosis and their correlation with JIA subtype and markers of inflammation and atherosclerosis.

Methods

Thirty-nine newly diagnosed patients with JIA (26 girls; mean age, 13.2 ± 2.6 years) and 27 healthy controls (9 girls; mean age, 13.6 ± 3.4 years) were included in the study. Twelve patients had oligoarthritis, fifteen had extended oligoarthritis and twelve had rheumatoid factor–negative polyarthritis. IMT of the common carotid artery was determined by ultrasonography, carotid-femoral pulse wave velocity (cfPWV) and augmentation index adjusted to a heart rate of 75 beats/min (AIx@75) were determined by applanation tonometry. The serum levels of atherosclerosis-related biomarkers, such as asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and adiponectin, were measured by enzyme-linked immunosorbent assay.

Results

Mean IMT (0.46 ± 0.04 vs. 0.42 ± 0.04 mm; p = 0.0003) and MPO concentration (115.2 [95 % confidence interval {95 % CI}, 97.4–136.3] vs. 57.6 [95 % CI, 47.1–70.3] ng/ml; p < 0.0001) were higher in the patients with JIA than in the control subjects. The cfPWV, AIx@75 and serum ADMA and adiponectin levels did not significantly differ between the groups and JIA subtypes. Serum adiponectin level correlated negatively with AIx@75 in patients with JIA (r = −0.38; p < 0.05).

Conclusions

Patients with JIA have increased mean IMT and elevated MPO levels at early stages of the disease. AIx@75 was inversely independently associated with adiponectin level in the patients, suggesting that lower adiponectin levels might influence arterial subclinical stiffening in patients with newly diagnosed JIA.
Literature
1.
go back to reference Al-Matar MJ, Petty RE, Tucker LB, Malleson PN, Schroeder ML, Cabral DA. The early pattern of joint involvement predicts disease progression in children with oligoarticular (pauciarticular) juvenile rheumatoid arthritis. Arthritis Rheum. 2002;46:2708–15.PubMedCrossRef Al-Matar MJ, Petty RE, Tucker LB, Malleson PN, Schroeder ML, Cabral DA. The early pattern of joint involvement predicts disease progression in children with oligoarticular (pauciarticular) juvenile rheumatoid arthritis. Arthritis Rheum. 2002;46:2708–15.PubMedCrossRef
2.
go back to reference Selvaag AM, Lien G, Sørskaar D, Vinje O, Førre Ø, Flatø B. Early disease course and predictors of disability in juvenile rheumatoid arthritis and juvenile spondyloarthropathy: a 3 year prospective study. J Rheumatol. 2005;32:1122–30.PubMed Selvaag AM, Lien G, Sørskaar D, Vinje O, Førre Ø, Flatø B. Early disease course and predictors of disability in juvenile rheumatoid arthritis and juvenile spondyloarthropathy: a 3 year prospective study. J Rheumatol. 2005;32:1122–30.PubMed
3.
go back to reference Minden K, Niewerth M, Listing J, Biedermann T, Bollow M, Schöntube M, et al. Long-term outcome in patients with juvenile idiopathic arthritis. Arthritis Rheum. 2002;46:2392–401.PubMedCrossRef Minden K, Niewerth M, Listing J, Biedermann T, Bollow M, Schöntube M, et al. Long-term outcome in patients with juvenile idiopathic arthritis. Arthritis Rheum. 2002;46:2392–401.PubMedCrossRef
4.
go back to reference Flatø B, Lien G, Smerdel A, Vinje O, Dale K, Johnston V, et al. Prognostic factors in juvenile rheumatoid arthritis: a case–control study revealing early predictors and outcome after 14.9 years. J Rheumatol. 2003;30:386–93.PubMed Flatø B, Lien G, Smerdel A, Vinje O, Dale K, Johnston V, et al. Prognostic factors in juvenile rheumatoid arthritis: a case–control study revealing early predictors and outcome after 14.9 years. J Rheumatol. 2003;30:386–93.PubMed
5.
go back to reference Nordal E, Zak M, Aalto K, Berntson L, Fasth A, Herlin T, et al. Ongoing disease activity and changing categories in a long-term Nordic cohort study of juvenile idiopathic arthritis. Arthritis Rheum. 2011;63:2809–18.PubMedCrossRef Nordal E, Zak M, Aalto K, Berntson L, Fasth A, Herlin T, et al. Ongoing disease activity and changing categories in a long-term Nordic cohort study of juvenile idiopathic arthritis. Arthritis Rheum. 2011;63:2809–18.PubMedCrossRef
7.
go back to reference Kwaśny-Krochin B, Głuszko P, Undas A. Plasma asymmetric dimethylarginine in active rheumatoid arthritis: links with oxidative stress and inflammation. Pol Arch Med Wewn. 2012;122:270–6.PubMed Kwaśny-Krochin B, Głuszko P, Undas A. Plasma asymmetric dimethylarginine in active rheumatoid arthritis: links with oxidative stress and inflammation. Pol Arch Med Wewn. 2012;122:270–6.PubMed
8.
go back to reference Schäffler A, Ehling A, Neumann E, Herfarth H, Tarner I, Schölmerich J, et al. Adipocytokines in synovial fluid. JAMA. 2003;290:1709–10.PubMedCrossRef Schäffler A, Ehling A, Neumann E, Herfarth H, Tarner I, Schölmerich J, et al. Adipocytokines in synovial fluid. JAMA. 2003;290:1709–10.PubMedCrossRef
9.
go back to reference Pruunsild C, Heilman K, Zilmer K, Uibo K, Liivamägi H, Talvik T, et al. Plasma level of myeloperoxidase in children with juvenile idiopathic arthritis (a pilot study). Cent Eur J Med. 2010;5:36–40. Pruunsild C, Heilman K, Zilmer K, Uibo K, Liivamägi H, Talvik T, et al. Plasma level of myeloperoxidase in children with juvenile idiopathic arthritis (a pilot study). Cent Eur J Med. 2010;5:36–40.
12.
go back to reference Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, et al. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37:481–94.PubMedCrossRef Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, et al. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37:481–94.PubMedCrossRef
13.
go back to reference del Rincón ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001;44:2737–45.PubMedCrossRef del Rincón ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001;44:2737–45.PubMedCrossRef
14.
go back to reference Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59:1690–7.PubMedCrossRef Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59:1690–7.PubMedCrossRef
15.
go back to reference Mäki-Petäjä KM, Hall FC, Booth AD, Wallace SM. Yasmin, Bearcroft PW, et al. Rheumatoid arthritis is associated with increased aortic pulse-wave velocity, which is reduced by anti-tumor necrosis factor-α therapy. Circulation. 2006;114:1185–92.PubMedCrossRef Mäki-Petäjä KM, Hall FC, Booth AD, Wallace SM. Yasmin, Bearcroft PW, et al. Rheumatoid arthritis is associated with increased aortic pulse-wave velocity, which is reduced by anti-tumor necrosis factor-α therapy. Circulation. 2006;114:1185–92.PubMedCrossRef
16.
go back to reference Mäki-Petäjä KM, Elkhawad M, Cheriyan J, Joshi FR, Ostör AJ, Hall FC, et al. Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation. 2012;126:2473–80.PubMedCrossRef Mäki-Petäjä KM, Elkhawad M, Cheriyan J, Joshi FR, Ostör AJ, Hall FC, et al. Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation. 2012;126:2473–80.PubMedCrossRef
17.
go back to reference Kavey RE, Allada V, Daniels SR, Hayman LL, McCrindle BW, Newburger JW, et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2006;114:2710–38.PubMedCrossRef Kavey RE, Allada V, Daniels SR, Hayman LL, McCrindle BW, Newburger JW, et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2006;114:2710–38.PubMedCrossRef
18.
go back to reference Vlahos AP, Theocharis P, Bechlioulis A, Naka KK, Vakalis K, Papamichael ND, et al. Changes in vascular function and structure in juvenile idiopathic arthritis. Arthritis Care Res. 2011;63:1736–44.CrossRef Vlahos AP, Theocharis P, Bechlioulis A, Naka KK, Vakalis K, Papamichael ND, et al. Changes in vascular function and structure in juvenile idiopathic arthritis. Arthritis Care Res. 2011;63:1736–44.CrossRef
19.
go back to reference Breda L, Di Marzio D, Giannini C, Gaspari S, Nozzi M, Scarinci A, et al. Relationship between inflammatory markers, oxidant-antioxidant status and intima-media thickness in prepubertal children with juvenile idiopathic arthritis. Clin Res Cardiol. 2013;102:63–71.PubMedCrossRef Breda L, Di Marzio D, Giannini C, Gaspari S, Nozzi M, Scarinci A, et al. Relationship between inflammatory markers, oxidant-antioxidant status and intima-media thickness in prepubertal children with juvenile idiopathic arthritis. Clin Res Cardiol. 2013;102:63–71.PubMedCrossRef
20.
go back to reference Satija M, Yadav TP, Sachdev N, Chhabra A, Jahan A, Dewan V. Endothelial function, arterial wall mechanics and intima media thickness in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2014;32:432–9.PubMed Satija M, Yadav TP, Sachdev N, Chhabra A, Jahan A, Dewan V. Endothelial function, arterial wall mechanics and intima media thickness in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2014;32:432–9.PubMed
21.
go back to reference Heilman K, Zilmer M, Zilmer K, Kool P, Tillmann V. Elevated plasma adiponectin and decreased plasma homocysteine and asymmetric dimethylarginine in children with type 1 diabetes. Scand J Clin Lab Invest. 2009;69:85–91.PubMedCrossRef Heilman K, Zilmer M, Zilmer K, Kool P, Tillmann V. Elevated plasma adiponectin and decreased plasma homocysteine and asymmetric dimethylarginine in children with type 1 diabetes. Scand J Clin Lab Invest. 2009;69:85–91.PubMedCrossRef
22.
go back to reference Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31:390–2.PubMed Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31:390–2.PubMed
23.
go back to reference Sharman JE, Lim R, Qasem AM, Coombes JS, Burgess MI, Franco J, et al. Validation of a generalized transfer function to noninvasively derive central blood pressure during exercise. Hypertension. 2006;47:1203–8.PubMedCrossRef Sharman JE, Lim R, Qasem AM, Coombes JS, Burgess MI, Franco J, et al. Validation of a generalized transfer function to noninvasively derive central blood pressure during exercise. Hypertension. 2006;47:1203–8.PubMedCrossRef
24.
go back to reference Wilkinson IB, Fuchs SA, Jansen IM, Spratt JC, Murray GD, Cockcroft JR, et al. Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis. J Hypertens. 1998;16:2079–84.PubMedCrossRef Wilkinson IB, Fuchs SA, Jansen IM, Spratt JC, Murray GD, Cockcroft JR, et al. Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis. J Hypertens. 1998;16:2079–84.PubMedCrossRef
25.
go back to reference Jourdan C, Wühl E, Litwin M, Fahr K, Trelewicz J, Jobs K, et al. Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertens. 2005;23:1707–15.PubMedCrossRef Jourdan C, Wühl E, Litwin M, Fahr K, Trelewicz J, Jobs K, et al. Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertens. 2005;23:1707–15.PubMedCrossRef
26.
go back to reference Dupont WD, Plummer Jr WD. Power and sample size calculations: a review and computer program. Control Clin Trials. 1990;11:116–28.PubMedCrossRef Dupont WD, Plummer Jr WD. Power and sample size calculations: a review and computer program. Control Clin Trials. 1990;11:116–28.PubMedCrossRef
27.
go back to reference Stamp LK, Khalilova I, Tarr JM, Senthilmohan R, Turner R, Haigh RC, et al. Myeloperoxidase and oxidative stress in rheumatoid arthritis. Rheumatology (Oxford). 2012;51:1796–803.CrossRef Stamp LK, Khalilova I, Tarr JM, Senthilmohan R, Turner R, Haigh RC, et al. Myeloperoxidase and oxidative stress in rheumatoid arthritis. Rheumatology (Oxford). 2012;51:1796–803.CrossRef
28.
go back to reference Nicholls SJ, Hazen SL. Myeloperoxidase and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2005;25:1102–11.PubMedCrossRef Nicholls SJ, Hazen SL. Myeloperoxidase and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2005;25:1102–11.PubMedCrossRef
29.
go back to reference Wang W, Jian Z, Guo J, Ning X. Increased levels of serum myeloperoxidase in patients with active rheumatoid arthritis. Life Sci. 2014;117:19–23.PubMedCrossRef Wang W, Jian Z, Guo J, Ning X. Increased levels of serum myeloperoxidase in patients with active rheumatoid arthritis. Life Sci. 2014;117:19–23.PubMedCrossRef
30.
go back to reference Kals J, Kampus P, Kals M, Teesalu R, Zilmer K, Pulges A, et al. Arterial elasticity is associated with endothelial vasodilatory function and asymmetric dimethylarginine level in healthy subjects. Scand J Clin Lab Invest. 2007;67:536–44.PubMedCrossRef Kals J, Kampus P, Kals M, Teesalu R, Zilmer K, Pulges A, et al. Arterial elasticity is associated with endothelial vasodilatory function and asymmetric dimethylarginine level in healthy subjects. Scand J Clin Lab Invest. 2007;67:536–44.PubMedCrossRef
31.
go back to reference Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation. 1999;99:3092–5.PubMedCrossRef Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation. 1999;99:3092–5.PubMedCrossRef
32.
go back to reference Tain YL, Huang LT. Asymmetric dimethylarginine: clinical applications in pediatric medicine. J Formos Med Assoc. 2011;110:70–7.PubMedCrossRef Tain YL, Huang LT. Asymmetric dimethylarginine: clinical applications in pediatric medicine. J Formos Med Assoc. 2011;110:70–7.PubMedCrossRef
33.
go back to reference Chow WS, Cheung BM, Tso AW, Xu A, Wat NM, Fong CH, et al. Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. Hypertension. 2007;49:1455–61.PubMedCrossRef Chow WS, Cheung BM, Tso AW, Xu A, Wat NM, Fong CH, et al. Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. Hypertension. 2007;49:1455–61.PubMedCrossRef
34.
go back to reference Schnabel R, Messow CM, Lubos E, Espinola-Klein C, Rupprecht HJ, Bickel C, et al. Association of adiponectin with adverse outcome in coronary artery disease patients: results from the AtheroGene study. Eur Heart J. 2008;29:649–57.PubMedCrossRef Schnabel R, Messow CM, Lubos E, Espinola-Klein C, Rupprecht HJ, Bickel C, et al. Association of adiponectin with adverse outcome in coronary artery disease patients: results from the AtheroGene study. Eur Heart J. 2008;29:649–57.PubMedCrossRef
35.
go back to reference Aulie HA, Selvaag AM, Günther A, Lilleby V, Molberg O, Hartmann A, et al. Arterial haemodynamics and coronary artery calcification in adult patients with juvenile idiopathic arthritis. Ann Rheum Dis. In press. 10.1136/annrheumdis-2013-204804. Aulie HA, Selvaag AM, Günther A, Lilleby V, Molberg O, Hartmann A, et al. Arterial haemodynamics and coronary artery calcification in adult patients with juvenile idiopathic arthritis. Ann Rheum Dis. In press. 10.​1136/​annrheumdis-2013-204804.
Metadata
Title
Increased carotid artery intima-media thickness and myeloperoxidase level in children with newly diagnosed juvenile idiopathic arthritis
Authors
Jaanika Ilisson
Maksim Zagura
Kersti Zilmer
Erik Salum
Kaire Heilman
Anneli Piir
Vallo Tillmann
Jaak Kals
Mihkel Zilmer
Chris Pruunsild
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2015
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-015-0699-x

Other articles of this Issue 1/2015

Arthritis Research & Therapy 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
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