Dr. Gabay has received consulting fees, speaking fees, and/or honoraria from Abbott, Essex, Roche, Novartis, and Merck (less than $10,000 each).
Rheumatoid Arthritis Clinical Studies
Anti–apolipoprotein A-1 IgG predicts major cardiovascular events in patients with rheumatoid arthritis
Version of Record online: 6 MAY 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 9, pages 2640–2650, September 2010
How to Cite
Vuilleumier, N., Bas, S., Pagano, S., Montecucco, F., Guerne, P.-A., Finckh, A., Lovis, C., Mach, F., Hochstrasser, D., Roux-Lombard, P. and Gabay, C. (2010), Anti–apolipoprotein A-1 IgG predicts major cardiovascular events in patients with rheumatoid arthritis. Arthritis & Rheumatism, 62: 2640–2650. doi: 10.1002/art.27546
- Issue online: 31 AUG 2010
- Version of Record online: 6 MAY 2010
- Manuscript Accepted: 27 APR 2010
- Manuscript Received: 17 FEB 2010
- Télémaque Institute and the Fondation Gustave et Simone Prevot
- Lucie et Ernst Schmidheiny Foundation
- Swiss National Science Foundation. Grant Numbers: 310030-118245, 320000-119728
To determine whether anti–apolipoprotein A-1 (anti–Apo A-1) IgG are associated with major cardiovascular events in patients with rheumatoid arthritis (RA).
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.
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.
Anti–Apo A-1 IgG is an independent predictor of major cardiovascular events in RA, possibly by affecting vulnerability to atherosclerotic plaque.