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

Clin Res Cardiol. 2013 Jan;102(1):63-71. doi: 10.1007/s00392-012-0496-3. Epub 2012 Aug 11.

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.

MeSH terms

  • Age Factors
  • Antioxidants / analysis*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Juvenile / blood
  • Arthritis, Juvenile / complications*
  • Arthritis, Juvenile / immunology
  • Arthritis, Juvenile / therapy
  • Arthritis, Juvenile / urine
  • Atherosclerosis / blood
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / etiology*
  • Atherosclerosis / immunology
  • Atherosclerosis / therapy
  • Atherosclerosis / urine
  • Biomarkers / blood
  • Biomarkers / urine
  • Blood Pressure
  • Carotid Arteries / diagnostic imaging*
  • Carotid Intima-Media Thickness*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Linear Models
  • Lipids / blood
  • Longitudinal Studies
  • Male
  • Plaque, Atherosclerotic
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Sexual Development
  • Time Factors
  • Treatment Outcome
  • Ultrasonography, Doppler, Color*

Substances

  • Antioxidants
  • Antirheumatic Agents
  • Biomarkers
  • Inflammation Mediators
  • Lipids