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Comparison With Cystatin C and C-Reactive Protein

Shoji Shinkai, MD, PhD, MPH; Paulo H. M. Chaves, MD, PhD; Yoshinori Fujiwara, MD, PhD; Shuichiro Watanabe, MD, PhD; Hiroshi Shibata, MD, PhD; Hideyo Yoshida, MD, PhD; Takao Suzuki, MD, PhD

Arch Intern Med. 2008;168(2):200-206.

Background  The clinicoepidemiologic relevance of moderately elevated concentrations of circulating β₂-microglobulin (β₂-M) has not been established.

Methods  We examined whether serum β₂-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 Gerontology Longitudinal Interdisciplinary Study on Aging. Cox proportional hazards models were used to examine independent associations between baseline β₂-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 β₂-M concentration and mortality risk, even after multiple adjustments. Compared with individuals in the lowest tertile of serum β₂-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% CI, 1.92-4.20) tertiles had a substantially increased mortality risk. Respective values were 1.28 (95% CI, 0.86-1.90) and 1.95 (95% CI, 1.31-2.89) for cystatin C and 1.39 (95% CI, 0.98-1.98) and 1.44 (95% CI, 1.00-2.06) 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 β₂-M (0.70; 95% CI, 0.66-0.74), followed by cystatin C (0.66; 95% CI, 0.62-0.70) and CRP (0.57; 95% CI, 0.53-0.61). Additional adjustment for renal function measures, inflammation markers, or both only partially reduced the association between β₂-M and mortality.

Conclusion  Serum β₂-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.

Author Affiliations: Departments of Community Health (Drs Shinkai and Fujiwara) and Epidemiology (Drs Yoshida and Suzuki), Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland (Dr Chaves); and Major in Gerontology, Graduate School of International Studies, Obirin University, Tokyo (Drs Watanabe and Shibata).

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