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.
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.
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, 390459 & ICD-10, 0099), 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.
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.
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