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.
Subgroup Analyses of a Novel Baseline Biomarker of Acute-Phase Serum Amyloid A (A-SAA) and Serum Interleukin2 Receptor Alpha (sIL-2Ra) That Predicted Long-Term (18 to 35 yrs) Mortality in a Cohort of Incident Rheumatoid Arthritis (RA) and Non-RA.
Masi1, Alfonse T., Aldag1, Jean C., Sipe2, Jean D.
University of Illinois College of Medicine at Peoria, Peoria, IL
Boston University School of Medicine, Boston, MA
Background/Purpose:
Research on biomarkers of mortality has high priority, especially for cardiovascular causes. A novel biomarker of either elevated serum A-SAA or sIL-2Ra levels predicted total mortality in decades-long follow-up of a prospective cohort (A&R 2010;62:S19). The biomarker is now analyzed for prediction of mortality in cohort subgroups.
Methods:
Cohorts in this community-based (n = 21,061 adults) study of risk factors for RA enrolled in 1974. The pre-RA cases had clinical onset, 3 to 20 (mean 12) yrs, after entry (1977 – 1994). Controls (CN) were non-RA cohorts matched at entry (4CN: 1 pre-RA). Biomarker data were available on 192 (44 pre-RA, 148 CN) subjects, who were monitored for mortality, from 1992 thru 2009, excluding 12 pre- 1992 deaths. Baseline stored (-70°C) sera were assayed (ELISA) "blindly" for the combined biomarker. High sensitivity A-SAA was assayed (Hemagen kits) at Boston University (sensitivity 1 mg/ml). The sIL-2Ra was assayed (R & D Systems, high sensitivity kits) at Specialty Laboratories, Santa Monica, CA. Sex- and age - specific upper quartile (UQ) values of A-SAA and sIL-2Ra were determined to decrease such covariate confounding. Elevated baseline (1974) A-SAA (p = 0.048) and sIL-2Ra (CD 25), p = 0.036 separately predicted total mortality, from 1992 – 2009. The combined novel predictor is defined as an elevated UQ level of either biomarker. All cause, primary cardiovascular (CV) (ICD-9, 390–459 & ICD-10, 00–99), and all other combined mortality (non-CV) was monitored quarterly, from 1992 thru 2009. Subgroup analyses were performed for percentages of deaths, and hazard ratios (HR) of the novel biomarker by Cox regression models.
Results:
All causes deaths occurred in 64 (33.3%) of 192 total subjects (biomarker HR = 2.37 (1.44 – 3.90), p = 0.001). Comparative death outcomes in cohort subgroups, percentile mortality, and biomarker predictions (HRs) by the Cox Model are shown in the Table. Mortality was greater in RA (50.0%) vs CN (28.4%), p = 0.017. The biomarker similarly predicted mortality outcomes for RA (HR = 2.50) and CN (HR = 2.32) subgroups. Mortality prediction was significant for females [HR = 3.33 (1.66 – 6.71), p = 0.001], but not for males [HR = 1.54 (0.77 – 3.10), p = 0.225]. Mortality prediction was significant for younger (< 47 yrs) subjects at entry [HR = 3.98 (1.76 – 9.00), p = 0.001], but not for older cohorts [HR = 1.62 (0.85 – 3.10), p = 0.145]. The biomarker strongly predicted CV mortality [HR = 6.38 (2.25 – 18.09), p < 0.001], but not the remainder of deaths [HR = 1.62 (0.90 – 2.94), p = 0.111], as shown in Table.
Conclusion:
Baseline (1974) UQ levels of either serum A-SAA or sIL-2Ra predicted long-term (18 to 35 yrs) mortality, significantly for females (p = 0.001), younger cohorts (p = 0.001), and circulatory (p < 0.001) deaths. This novel biomarker deserves further testing as a long-term mortality predictor.
To cite this abstract, please use the following information:
Masi, Alfonse T., Aldag, Jean C., Sipe, Jean D.; Subgroup Analyses of a Novel Baseline Biomarker of Acute-Phase Serum Amyloid A (A-SAA) and Serum Interleukin2 Receptor Alpha (sIL-2Ra) That Predicted Long-Term (18 to 35 yrs) Mortality in a Cohort of Incident Rheumatoid Arthritis (RA) and Non-RA. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :112
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