en
Scientific article
English

Anti-apolipoprotein A-1 IgG predicts major cardiovascular events in patients with rheumatoid arthritis

Published inArthritis and rheumatism, vol. 62, no. 9, p. 2640-2650
Publication date2010
Abstract

OBJECTIVE: To determine whether anti-apolipoprotein A-1 (anti-Apo A-1) IgG are associated with major cardiovascular events in patients with rheumatoid arthritis (RA). METHODS: We determined anti-Apo A-1 IgG levels and the concentrations of cytokines, oxidized low-density lipoprotein (LDL), and matrix metalloproteinase 1 (MMP-1) MMP-2, MMP-3, and MMP-9 in sera from 133 patients with RA who did not have cardiovascular disease at baseline, all of whom were longitudinally followed up over a median period of 9 years. A major cardiovascular event was defined as a fatal or nonfatal stroke or acute coronary syndrome. The proinflammatory effects of anti-Apo A-1 IgG were assessed on human macrophages in vitro. RESULTS: During followup, the overall incidence of major cardiovascular events was 15% (20 of 133 patients). At baseline, anti-Apo A-1 IgG positivity was 17% and was associated with a higher incidence of major cardiovascular events (adjusted hazard ratio 4.2, 95% confidence interval 1.5-12.1). Patients who experienced a subsequent major cardiovascular event had higher circulating levels of anti-Apo A-1 IgG at baseline compared with those who did not have a major cardiovascular event. Receiver operating curve analysis showed that anti-Apo A-1 IgG was the strongest of all tested biomarkers for the prediction of a subsequent major cardiovascular event, with an area under the curve value of 0.73 (P = 0.0008). At the predefined and previously validated cutoff levels, the specificity and sensitivity of anti-Apo A-1 IgG to predict major cardiovascular events were 50% and 90%, respectively. Anti-Apo A-1 IgG positivity was associated with higher median circulating levels of interleukin-8 (IL-8), oxidized LDL, and MMP-9 and higher proMMP-9 activity as assessed by zymography. On human macrophages, anti-Apo A-1 IgG induced a significant dose-dependent increase in IL-8 and MMP-9 levels and proMMP-9 activity. CONCLUSION: Anti-Apo A-1 IgG is an independent predictor of major cardiovascular events in RA, possibly by affecting vulnerability to atherosclerotic plaque.

Keywords
  • Acute Coronary Syndrome/blood/epidemiology/*immunology
  • Aged
  • Apolipoprotein A-I/*immunology
  • Arthritis, Rheumatoid/blood/epidemiology/*immunology
  • Autoantibodies/*blood/pharmacology
  • Biological Markers/blood
  • Cells, Cultured
  • Comorbidity
  • Cytokines/blood
  • Female
  • Humans
  • Immunoglobulin G/blood
  • Lipoproteins, LDL/blood
  • Longitudinal Studies
  • Macrophages/drug effects/metabolism
  • Male
  • Matrix Metalloproteinases/blood
  • Predictive Value of Tests
  • Stroke/blood/epidemiology/*immunology
  • Switzerland/epidemiology
Citation (ISO format)
VUILLEUMIER, Nicolas et al. Anti-apolipoprotein A-1 IgG predicts major cardiovascular events in patients with rheumatoid arthritis. In: Arthritis and rheumatism, 2010, vol. 62, n° 9, p. 2640–2650. doi: 10.1002/art.27546
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ISSN of the journal0004-3591
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Creation23.05.2012 09:01:02
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