Skip to main content

01.01.2013 | Original Paper

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

verfasst von: L. Breda, D. Di Marzio, C. Giannini, S. Gaspari, M. Nozzi, A. Scarinci, F. Chiarelli, A. Mohn

Erschienen in: Clinical Research in Cardiology | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

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.
Literatur
2.
3.
Zurück zum Zitat 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 57:125–132PubMedCrossRef 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 57:125–132PubMedCrossRef
4.
Zurück zum Zitat Sattar N, McCarey DW, Capell H, McInnes IB (2003) Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 108:2957–2963PubMedCrossRef Sattar N, McCarey DW, Capell H, McInnes IB (2003) Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 108:2957–2963PubMedCrossRef
5.
Zurück zum Zitat Maziere C, Auclair M, Maziere JC (1994) Tumor necrosis factor enhances low density lipoprotein oxidative modification by monocytes and endothelial cells. FEBS Lett 338:43–46PubMedCrossRef Maziere C, Auclair M, Maziere JC (1994) Tumor necrosis factor enhances low density lipoprotein oxidative modification by monocytes and endothelial cells. FEBS Lett 338:43–46PubMedCrossRef
6.
Zurück zum Zitat 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 48:1833–1840PubMedCrossRef 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 48:1833–1840PubMedCrossRef
7.
Zurück zum Zitat 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 104:2943–2947PubMedCrossRef 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 104:2943–2947PubMedCrossRef
8.
Zurück zum Zitat 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 111:61–66PubMedCrossRef 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 111:61–66PubMedCrossRef
9.
Zurück zum Zitat 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 197:448–456PubMedCrossRef 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 197:448–456PubMedCrossRef
10.
Zurück zum Zitat 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 31:390–392PubMed 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 31:390–392PubMed
11.
Zurück zum Zitat Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A (1997) Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 40:1202–1209PubMed Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A (1997) Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 40:1202–1209PubMed
12.
Zurück zum Zitat 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 29:581–593PubMed 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 29:581–593PubMed
13.
Zurück zum Zitat Roberts LJ, Morrow JD (2000) Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med 28:505–513PubMedCrossRef Roberts LJ, Morrow JD (2000) Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med 28:505–513PubMedCrossRef
14.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 74:1399–1406PubMedCrossRef 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 74:1399–1406PubMedCrossRef
16.
Zurück zum Zitat 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 28:2094–2101PubMedCrossRef 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 28:2094–2101PubMedCrossRef
17.
Zurück zum Zitat 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 63:1736–1744CrossRef 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 63:1736–1744CrossRef
18.
Zurück zum Zitat 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 100:241–247CrossRef 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 100:241–247CrossRef
19.
Zurück zum Zitat 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 26:1701–1704PubMed 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 26:1701–1704PubMed
20.
Zurück zum Zitat Superko HR, Gadesam RR (2008) Is it LDL particle size or number that correlates with risk for cardiovascular disease? Curr Atheroscler Rep 10:377–385PubMedCrossRef Superko HR, Gadesam RR (2008) Is it LDL particle size or number that correlates with risk for cardiovascular disease? Curr Atheroscler Rep 10:377–385PubMedCrossRef
21.
Zurück zum Zitat White D, Fayez S, Doube A (2006) Atherogenic lipid profiles in rheumatoid arthritis. N Z Med J 119:U2125PubMed White D, Fayez S, Doube A (2006) Atherogenic lipid profiles in rheumatoid arthritis. N Z Med J 119:U2125PubMed
22.
Zurück zum Zitat 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 100:2637CrossRef 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 100:2637CrossRef
23.
Zurück zum Zitat Montuschi P, Barnes PJ, Roberts LA (2004) Isoprostanes: markers and mediators of oxidative stress. FASEB J 18:1791–1800PubMedCrossRef Montuschi P, Barnes PJ, Roberts LA (2004) Isoprostanes: markers and mediators of oxidative stress. FASEB J 18:1791–1800PubMedCrossRef
24.
Zurück zum Zitat 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 38:366–371PubMedCrossRef 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 38:366–371PubMedCrossRef
25.
Zurück zum Zitat 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 52:2293–2299PubMedCrossRef 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 52:2293–2299PubMedCrossRef
26.
Zurück zum Zitat 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 57:287–293PubMedCrossRef 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 57:287–293PubMedCrossRef
27.
Zurück zum Zitat 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 57:1074–1080PubMedCrossRef 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 57:1074–1080PubMedCrossRef
28.
Zurück zum Zitat 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 60:1496–1507PubMedCrossRef 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 60:1496–1507PubMedCrossRef
29.
Zurück zum Zitat Nam BH, Kannel WB, D’Agostino RB (2006) Search for an optimal atherogenic lipid risk profile: from the Framingham-study. Am J Cardiol 97:372–375PubMedCrossRef Nam BH, Kannel WB, D’Agostino RB (2006) Search for an optimal atherogenic lipid risk profile: from the Framingham-study. Am J Cardiol 97:372–375PubMedCrossRef
30.
Zurück zum Zitat 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 115:89–98PubMedCrossRef 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 115:89–98PubMedCrossRef
31.
Zurück zum Zitat Gonzalez-Juanatey C, Gonzalez-Gay MA (2004) Long-term rheumatoid arthritis and endothelial dysfunction. Atherosclerosis 176:197–198PubMedCrossRef Gonzalez-Juanatey C, Gonzalez-Gay MA (2004) Long-term rheumatoid arthritis and endothelial dysfunction. Atherosclerosis 176:197–198PubMedCrossRef
32.
Zurück zum Zitat 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 32:1213–1218PubMed 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 32:1213–1218PubMed
33.
Zurück zum Zitat 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 66:880–885PubMedCrossRef 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 66:880–885PubMedCrossRef
34.
Zurück zum Zitat 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 3:1224–1230PubMedCrossRef 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 3:1224–1230PubMedCrossRef
Metadaten
Titel
Relationship between inflammatory markers, oxidant–antioxidant status and intima-media thickness in prepubertal children with juvenile idiopathic arthritis
verfasst von
L. Breda
D. Di Marzio
C. Giannini
S. Gaspari
M. Nozzi
A. Scarinci
F. Chiarelli
A. Mohn
Publikationsdatum
01.01.2013
Verlag
Springer-Verlag
Erschienen in
Clinical Research in Cardiology / Ausgabe 1/2013
Print ISSN: 1861-0684
Elektronische ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-012-0496-3

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.