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

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Published in Arthritis and Rheumatism. 2010, vol. 62, no. 9, p. 2640-2650
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/*immunologyAgedApolipoprotein A-I/*immunologyArthritis, Rheumatoid/blood/epidemiology/*immunologyAutoantibodies/*blood/pharmacologyBiological Markers/bloodCells, CulturedComorbidityCytokines/bloodFemaleHumansImmunoglobulin G/bloodLipoproteins, LDL/bloodLongitudinal StudiesMacrophages/drug effects/metabolismMaleMatrix Metalloproteinases/bloodPredictive Value of TestsStroke/blood/epidemiology/*immunologySwitzerland/epidemiology
PMID: 20506304
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Research groups Biologie du myocarde (22)
La protéomique au service de la clinique (270)
Mécanisme de l'inflammation articulaire (44)
L'athérosclérose et ses complications cliniques (591)
Interfaces Homme-machine en milieu clinique (610)
Etude de l'activation des monocytes/macrophages et des polynucléaires neutrophiles (779)
(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 https://archive-ouverte.unige.ch/unige:21384

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Deposited on : 2012-05-23

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