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


CONCLUSIONS
Anti-Apo A-1 IgG is an independent predictor of major cardiovascular events in RA, possibly by affecting vulnerability to atherosclerotic plaque.
Vuilleumier
Nicolas
N
Geneva University Hospitals, Geneva, Switzerland. nicolas.vuilleumier@hcuge.ch
Bas
Sylvette
S
Pagano
Sabrina
S
Montecucco
Fabrizio
F
Guerne
Pierre-André
PA
Finckh
Axel
A
Lovis
Christian
C
Mach
François
F
Hochstrasser
Denis
D
Roux-Lombard
Pascale
P
Gabay
Cem
C
D054058:Acute Coronary Syndrome / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D000368:Aged; D016632:Apolipoprotein A-I / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D015897:Comorbidity; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008137:Longitudinal Studies; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood; D011237:Predictive Value of Tests; D020521:Stroke / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D013557:Switzerland / Q000453:epidemiology
D016632:Apolipoprotein A-I; D001323:Autoantibodies; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D020782:Matrix Metalloproteinases