β2-microglobulin for risk stratification of total mortality in the elderly population -: Comparison with cystatin C and C-reactive protein

Background: The clinicoepidermiologic relevance of moderately elevated concentrations of circulating beta(2)-microglobulin (beta(2)-M) has not been established. Methods: We examined whether serum beta(2)-M concentration independently predicts total mortality in community-dwelling older populations and compared its predictive value with that of cystatin C and C-reactive protein (CRP) using a prospective cohort study of 1034 initially nondisabled persons 65 years and older as part of the Tokyo Metropolitan Institute of Geronotology Longitudinal Interdisciplinary Study on Aging. Cox proportional hazards models were used to examine independent associations between baseline beta(2)-M levels and total mortality. Results: During a median follow-up of 7.9 years, 223 persons died. A strong dose-response relationship was found between baseline serum beta(2)-M concentration and mortality risk, even after multiple adjustments. Compared with individuals in the lowest tertile of serum beta(2)-M concentration, those in the middle (hazard ratio, 2.02; 95% confidence interval [CI], 1.35-3.04) and highest (hazard ratio, 2.84; 95% CL 1.92-4.20) tertiles had a substantially increased mortality risk. Respective values were 1.28 (95% Cl, 0.86-1.90) and 1.95 (95% Cl, 1.31-2.89) for cystatin C and 1.39 (95% Cl, 0.98-1.98) and 1.44 (95% Cl, 1.002.06) for CRP; only the highest tertiles showed significantly higher mortality risks. The area under the receiver operating characteristic curve for 8-year mortality was greatest for beta(2)-M (0.70; 95% CI, 0.66-0.74), followed by cystatin C (0.66; 95% Cl, 0.62-0.70) and CRP (0.57; 95% Cl, 0.53-0.61). Additional adjustment for renal function measures, inflammation markers, or both only partially reduced the association between beta(2)-M and mortality. Conclusions: Serum beta(2)-M is an independent predictor of total mortality in a general population of older adults and may be a better predictor than cystatin C or CRP.