Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Serum Cytokine Levels Predict Mortality Among Postmenopausal Women Reporting Rheumatoid Arthritis.
Sokolove1, Jeremy, Robinson2, William H., Walitt3, Brian T., Deane4, Kevin D., Chang5, Yuefang, Tracy6, Russell, Holers7, V. Michael
Stanford University, Palo Alto, CA
Stanford University, Stanford, CA
Washington Hospital Center, Washington, DC
University of Colorado School of Medicine, Aurora, CO
University of Pittsburgh, Pittsburgh, PA
University of Vermont, Colchester, VT
Univ of Colorado School of Med, Aurora, CO
Rheumatoid arthritis (RA) is associated with increased risk of total mortality, which is in part explained by increased cardiovascular (CV) mortality. We sought to determine whether levels of plasma cytokines could further inform risk of mortality among the anti-CCP2+ and anti-CCP2 negative RA population.
We performed multiplex profiling of 17 cytokines in stored baseline plasma from postmenopausal women sampled from the Women's Health Initiative (WHI) study cohort who self-reported RA. We additionally assessed for the presence of anti-CCP2 antibodies and rheumatoid factor (RF) using commercial ELISA kits and the HLA shared epitope (SE) by PCR. Cox proportional hazards regression was used to model the relationship of plasma cytokine levels (in quartiles) to total mortality using follow-up data through April 2009 (mean (SD) follow-up time= 10.2 (3.0) years). Analyses were weighted to reflect the sampling from the WHI cohort. Women with a baseline report of CVD or cancer were excluded. To maximize true clinical RA diagnoses, we limited our analysis to women who were either 1) anti-CCP2+ (n=512; 71 deaths), or 2) anti-CCP2 negative (n=272; 36 deaths) with self-reported use of disease modifying anti-rheumatic drugs.
The women in this study had a mean age of 62.8 years at baseline and 64.5% were white. Among anti-CCP2+ subjects, higher levels of IL-1b, IL-2, IL-6, IL-13, and MCP-1 predicted higher total mortality in age-adjusted models. After additional adjustment for RF, SE and additional risk factors including hypertension, ever smoking, and ethnicity, only higher IL-6 remained a significant predictor of total mortality (HR (95%CI) for highest quartile (Q4) vs. lowest quartile (Q1)=3.03, 1.148.03; P=0.02).
Among anti-CCP2 negative subjects, higher plasma MCP-1 levels strongly predicted total mortality and this relationship persisted even after adjustment for RF, SE, and additional risk factors (HR Q4 vs. Q1: 3.20, 1.139.02). Interestingly, elevated plasma IL-2, was associated with reduced age-adjusted mortality (HR Q4 vs. Q1: 0.40, 0.160.99; p=0.02). However, this association was attenuated after adjustment for RF, SE, hypertension, ever smoking, and ethnicity (HR Q4 vs. Q1=0.49, 0.181.33, p=0.06).
In addition to the increased mortality rates we have previously reported among anti-CCP2+ subjects, elevated levels of serum cytokines, especially IL-6, predict a further increased risk of total mortality. Among anti-CCP2 negative subjects, higher levels of MCP-1 and lower levels of IL-2 were associated with increased risk of total mortality. The mortality risk associated with lower levels of plasma IL-2 perhaps suggests spontaneous activation of autoreactive T cells as has been associated with RA as well as CVD.
To cite this abstract, please use the following information:
Sokolove, Jeremy, Robinson, William H., Walitt, Brian T., Deane, Kevin D., Chang, Yuefang, Tracy, Russell, et al; Serum Cytokine Levels Predict Mortality Among Postmenopausal Women Reporting Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :388