Serum beta-2 microglobulin concentration predicts cardiovascular and all-cause mortality

Abstract

BACKGROUND: This study sought to assess the association between beta-2-microglobulin (B2M) and mortality. B2M is expressed in all nucleated cells and shed from cell surfaces. Serum B2M level predicts mortality in multiple myeloma and chronic kidney disease.We hypothesized that it would predict cardiovascular and all-cause mortality in the general population. METHODS: 6,554 adult participants of the Third National Health and Nutrition Examination Survey were included in the analysis. Serum B2M level was used in multivariable Cox regression analysis to predict all-cause and cardiovascular mortality. Reclassification of mortality was assessed using integrative discrimination index (IDI) and category-less net reclassification improvement (NRI). RESULTS: During a median follow-up of 13.5 years (79,528 person-years), 2,524 and 1,150 participants died from all causes and cardiovascular causes, respectively. Serum B2M level increased with cardiometabolic and inflammatory risk factors. In unadjusted analysis, quartile 4 of B2M was significantly associated with all-cause (hazard ratio (HR)¼20.83, 95% CI: 14.35-30.24) and cardiovascular mortality (HR¼29.83, 95% CI: 16.00-55.62). After multivariable adjustment, the HRs remained significant (2.3, 95% CI: 1.65-3.21, for all-cause mortality and 1.89, 95% CI: 1.03-3.44, for cardiovascular mortality). Similar results were obtained in the subgroup with normal estimated glomerular filtration rate level. The Harrell’s C-statistics of B2M was 0.759 and 0.786 for all-cause and cardiovascular mortality respectively. Serum B2M, when added to Framingham Risk Score, showed significant reclassification in terms of IDI and category-less NRI. CONCLUSIONS: Serum B2M level is a powerful independent predictor of cardiovascular and all-cause mortality in the general population. Further studies are needed to see if it can be used to identify high risk individuals requiring intensive treatment.