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.

 Comparative Death Outcomes in Subgroups, and Biomarker Predictions by the Cox Model*
Cohort Subgroups, Mortality, and Cox Regression ModelsSubgroup # 1Subgroup # 2
RA (#1) vs CN (#2) Subgroups
Mortality (%)22 (50.0%) of 4442 (28.4%) of 148
Cox Regression Model HR (95% CI) of Deaths:2.50 (1.02–6.11)2.32 (1.26–4.27)
p Values (for Biomarker)p = 0.045p = 0.007
Females (# 1) vs Males (# 2)
Mortality (%)32 (29.1%) of 11032 (39.0%) of 82
Cox Regression Model HR (95% CI) of Deaths:3.33 (1.66–6.71)1.54 (0.77–3.10)
p Values (for Biomarker)p = 0.001p = 0.225
Younger (# 1) vs Older (# 2)
Mortality (%)26 (19.8%) of 13138 (62.3%) of 61
Cox Regression Model HR (95% CI) of Deaths:3.98 (1.76–9.00)1.62 (0.85–3.10)
p Values (for Biomarker)p = 0.001p = 0.145
CV (# 1) vs Non-CV (# 2) Deaths
Mortality (%)18 (9.4%) of 19246 (24.0%) of 192
Cox Regression Model HR (95% CI) of Deaths:6.38 (2.25–18.09)1.62 (0.90–2.94)
p Values (for Biomarker)p < 0.001p = 0.111
*Includes decades of age covariate

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
DOI:

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