Skip to main content

Advertisement

SpringerLink
Log in

Relationship between inflammatory markers, oxidant–antioxidant status and intima-media thickness in prepubertal children with juvenile idiopathic arthritis

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Objective

To investigate the presence of possible early atherosclerotic changes in a group of prepubertal children with juvenile idiopathic arthritis (JIA) and to establish the potential beneficial effects of 1-year treatment.

Materials and methods

Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), proinflammatory cytokines (IL-1β, IL-6, IFN-γ, TNF-α), lipid profile and oxidant–antioxidant status (urinary isoprostanes [PGF-2α]) were assessed in 38 JIA children (12M/26F, mean age 7.05 ± 2.39 years) and compared with 40 controls (18M/22F, mean age 6.34 ± 2.25 years). Carotid intima-media wall thickness (cIMT) was obtained and blood pressure was measured. All parameters were reassessed in JIA children after 1 year of therapy.

Results

At baseline JIA children presented compared to controls higher levels of inflammatory markers, proinflammatory cytokines, total cholesterol, LDL cholesterol, and PGF-2α (all p ≤ 0.01). Furthermore, blood pressure and cIMT were significantly increased (both p ≤ 0.01). After a 1-year treatment with non-steroid anti-inflammatory (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs), a significant reduction of all parameters was detected (all p ≤ 0.01). This was associated with a significant reduction in blood pressure and cIMT (both p ≤ 0.01). Within the JIA group, patients requiring etanercept presented worse laboratory values and cIMT measurements at baseline. Nevertheless, the same improvement of all parameters was obtained after a 1-year treatment. In stepwise multiple regression, LDL cholesterol and IL-1β were mainly related to cIMT.

Conclusion

Chronic and systemic inflammation seems to lead to early atherosclerotic abnormalities even in pre-pubertal JIA children. Substantial improvement can be obtained with 1-year of appropriate therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

JIA:

Juvenile idiopathic arthritis

CRP:

C-reactive protein

ESR:

Erythrocyte sedimentation rate

IL-1β:

Interleukin 1 beta

IL-6:

Interleukin 6

IFN-γ:

Interferon gamma

TNF-α:

Tumor necrosis factor alpha

PGF-2α:

Prostaglandin 2 alpha

cIMT:

Carotid intima-media wall thickness

NSAIDs:

Non-steroid anti-inflammatory drugs

DMARDs:

Disease-modifying antirheumatic drugs

RA:

Rheumatoid arthritis

ILAR:

International League of Associations for Rheumatology

VAS:

Visual analog scale

LOM:

Limitation of movement

CHAQ:

Child health assessment questionnaire

HDL:

High density lipoprotein

LDL:

Low density lipoprotein

BMI:

Body mass index

SDS:

Standard deviation score

SA-HRP:

Streptavidin-horseradish

FFA:

Free fatty acids

CV:

Cardiovascular

EMEA:

European Medicines Agency

FDA:

Food and Drug Administration

References

  1. Ravelli A, Martini A (2007) Juvenile idiophatic arthritis. Lancet 369:767–778

    Article  PubMed  CAS  Google Scholar 

  2. Woo P (2002) Cytokines and juvenile idiophatic arthritis. Curr Rheumatol Rep 4:452–457

    Article  PubMed  Google Scholar 

  3. Gonzalez-Gay MA, Gonzalez-Juanatey C, Lopez-Diaz MJ, Pineiro A, Garcia-Porrua C, Miranda-Filloy JA, Ollier WE, Martin J, Llorca J (2007) HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis. Arthritis Rheum 57:125–132

    Article  PubMed  CAS  Google Scholar 

  4. Sattar N, McCarey DW, Capell H, McInnes IB (2003) Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 108:2957–2963

    Article  PubMed  Google Scholar 

  5. Maziere C, Auclair M, Maziere JC (1994) Tumor necrosis factor enhances low density lipoprotein oxidative modification by monocytes and endothelial cells. FEBS Lett 338:43–46

    Article  PubMed  CAS  Google Scholar 

  6. del Rincon I, Williams K, Stern MP, Freeman GL, O’Leary DH, Escalante A (2003) Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum 48:1833–1840

    Article  PubMed  Google Scholar 

  7. Järvisalo MJ, Jartti L, Näntö-Salonen K, Irjala K, Rönnemaa T, Hartiala JJ, Celermajer DS, Raitakari OT (2001) Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high risk children. Circulation 104:2943–2947

    Article  PubMed  Google Scholar 

  8. Sorof JM, Alexandrov AV, Cardwell G, Portman RJ (2003) Carotid artery intimal-media thickness and left ventricular hypertrophy in children with elevated blood pressure. Pediatrics 111:61–66

    Article  PubMed  Google Scholar 

  9. Giannini C, de Giorgis T, Scarinci A, Ciampani M, Marcovecchio ML, Chiarelli F, Mohn A (2008) Obese related effects of inflammatory markers and insulin resistance on increased carotid intima-media thickness in pre-pubertal children. Atherosclerosis 197:448–456

    Article  PubMed  CAS  Google Scholar 

  10. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31:390–392

    PubMed  Google Scholar 

  11. Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A (1997) Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 40:1202–1209

    PubMed  CAS  Google Scholar 

  12. Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani (2006) Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest 29:581–593

    PubMed  CAS  Google Scholar 

  13. Roberts LJ, Morrow JD (2000) Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med 28:505–513

    Article  PubMed  CAS  Google Scholar 

  14. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents 1996 Pediatrics 98(4 Pt 1):649–658

  15. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R (1986) Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation 74:1399–1406

    Article  PubMed  CAS  Google Scholar 

  16. Amato M, Montorsi P, Ravani A, Oldani E, Galli S, Ravagnani PM, Tremoli E, Baldassarre D (2007) Carotid intima-media thickness by B-mode ultrasound as surrogate of coronary atherosclerosis: correlation with quantitative coronary angiography and coronary intravascular ultrasound findings. Eur Heart J 28:2094–2101

    Article  PubMed  Google Scholar 

  17. Vlahos AP, Theocharis P, Bechlioulis A, Naka KK, Vakalis K, Papamichael ND, Alfantaki S, Gartzonika K, Mavridis A, Michalis LK, Siamopoulou A (2011) Changes in vascular function and structure in juvenile idiopathic arthritis. Arthritis Care Res 63:1736–1744

    Article  Google Scholar 

  18. von Känel R, Carney RM, Zhao S, Whooley MA (2012) Heart rate variability and biomarkers of systemic inflammation in patients with stable coronary heart disease: findings from the Heart and Soul Study. Clin Res Cardiol 100:241–247

    Article  Google Scholar 

  19. Park YB, Lee SK, Lee WK, Suh CH, Lee CW, Lee CH, Song CH, Lee J (1999) Lipid profiles in untreated patients with rheumatoid arthritis. J Rheumatol 26:1701–1704

    PubMed  CAS  Google Scholar 

  20. Superko HR, Gadesam RR (2008) Is it LDL particle size or number that correlates with risk for cardiovascular disease? Curr Atheroscler Rep 10:377–385

    Article  PubMed  CAS  Google Scholar 

  21. White D, Fayez S, Doube A (2006) Atherogenic lipid profiles in rheumatoid arthritis. N Z Med J 119:U2125

    PubMed  Google Scholar 

  22. Praticò D, Iuliano L, Mauriello A, Spagnoli L, Lawson JA, Rokach J, Maclouf J, Violi F, FitzGerald GA (1997) Localization of distinct F2-isoprostanes in human atherosclerotic lesions. J Clin Invest 100:2637

    Article  Google Scholar 

  23. Montuschi P, Barnes PJ, Roberts LA (2004) Isoprostanes: markers and mediators of oxidative stress. FASEB J 18:1791–1800

    Article  PubMed  CAS  Google Scholar 

  24. Gonzalez-Juanatey C, Llorca J, Martin J, Gonzalez-Gay MA (2009) Carotid intima-media thickness predicts the development of cardiovascular events in patients with rheumatoid arthritis. Semin Arthritis Rheum 38:366–371

    Article  PubMed  Google Scholar 

  25. Goodson NJ, Symmons DP, Scott DG, Bunn D, Lunt M, Silman AJ (2005) Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort. Arthritis Rheum 52:2293–2299

    Article  PubMed  CAS  Google Scholar 

  26. Gonzalez-Juanatey C, Llorca J, Miranda-Filloy JA, Amigo-Diaz E, Testa A, Garcia-Porrua C, Martin J, Gonzalez-Gay MA (2007) Endothelial dysfunction in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors. Arthritis Rheum 57:287–293

    Article  PubMed  CAS  Google Scholar 

  27. Gonzalez-Juanatey C, Llorca J, Amigo-Diaz E, Dierssen T, Martin J, Gonzalez-Gay MA (2007) High prevalence of subclinical atherosclerosis in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors. Arthritis Rheum 57:1074–1080

    Article  PubMed  Google Scholar 

  28. Schanberg LE, Sandborg C, Barnhart HX, Ardoin SP, Yow E, Evans GW, Mieszkalski KL, Ilowite NT, Eberhard A, Levy DM, Kimura Y, von Scheven E, Silverman E, Bowyer SL, Punaro L, Singer NG, Sherry DD, McCurdy D, Klein-Gitelman M, Wallace C, Silver R, Wagner-Weiner L, Higgins GC, Brunner HI, Jung L, Soep JB, Reed A (2009) Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators. Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort. Arthritis Rheum 60:1496–1507

    Article  PubMed  Google Scholar 

  29. Nam BH, Kannel WB, D’Agostino RB (2006) Search for an optimal atherogenic lipid risk profile: from the Framingham-study. Am J Cardiol 97:372–375

    Article  PubMed  CAS  Google Scholar 

  30. Wang X, Feuerstein GZ, Gu JL, Lysko PG, Yue TL (1995) Interleukin-1 beta induces expression of adhesion molecules in human vascular smooth muscle cells and enhances adhesion of leukocytes to smooth muscle cells. Atherosclerosis 115:89–98

    Article  PubMed  CAS  Google Scholar 

  31. Gonzalez-Juanatey C, Gonzalez-Gay MA (2004) Long-term rheumatoid arthritis and endothelial dysfunction. Atherosclerosis 176:197–198

    Article  PubMed  CAS  Google Scholar 

  32. Jacobsson LT, Turesson C, Gülfe A, Kapetanovic MC, Petersson IF, Saxne T, Geborek P (2005) Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol 32:1213–1218

    PubMed  CAS  Google Scholar 

  33. Carmona L, Descalzo MA, Perez-Pampin E, Ruiz-Montesinos D, Erra A, Cobo T, Gómez-Reino JJ (2007) All-cause and cause-specific mortality in rheumatoid arthritis are not greater than expected when treated with tumour necrosis factor antagonists. Ann Rheum Dis 66:880–885

    Article  PubMed  CAS  Google Scholar 

  34. Tosetto A, Prati P, Baracchini C, Manara R, Rodeghiero F (2005) Age-adjusted reference limits for carotid intima-media thickness as better indicator of vascular risk: population-based estimates from the VITA project. J Thromb Haemost 3:1224–1230

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None to declare.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Chieti, Via dei Vestini 5, 66100, Chieti, Italy

    L. Breda, D. Di Marzio, C. Giannini, S. Gaspari, M. Nozzi, F. Chiarelli & A. Mohn

  2. Clinical Research Center, Ce.S.I, University of Chieti, Via dei Vestini 31, 66100, Chieti, Italy

    F. Chiarelli & A. Mohn

  3. Department of Cardiology, University of Chieti, Via dei Vestini 5, 66100, Chieti, Italy

    A. Scarinci

Authors
  1. L. Breda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Di Marzio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Giannini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Gaspari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Nozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Scarinci
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F. Chiarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. Mohn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Breda.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Breda, L., Di Marzio, D., Giannini, C. et al. Relationship between inflammatory markers, oxidant–antioxidant status and intima-media thickness in prepubertal children with juvenile idiopathic arthritis. Clin Res Cardiol 102, 63–71 (2013). https://doi.org/10.1007/s00392-012-0496-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-012-0496-3

Keywords

Search

Navigation