Biological pathways underlying the association of red cell distribution width and adverse clinical outcome: Results of a prospective cohort study

BACKGROUND Red cell distribution width (RDW) predicts disease outcome in several patient populations, but its prognostic value in addition to other disease parameters in unselected medical inpatients remains unclear. Our aim was to investigate the association of admission RDW levels and mortality adjusted for several disease pathways in unselected medical patients from a previous multicenter study. METHODS We included consecutive adult, medical patients at the time point of hospital admission through the emergency department into this observational, cohort study. The primary endpoint was mortality at 30-day. To study association of admission RDW and outcomes, we calculated regression analysis with step-wise inclusion of clinical and laboratory parameters from different biological pathways. RESULTS The 30-day mortality of the 4273 included patients was 5.6% and increased from 1.4% to 14.3% from the lowest to the highest RDW quartile. There was a strong association of RDW and mortality in unadjusted analysis (OR 1.32; 95%CI 1.27-1.39, p<0.001). RDW was strongly correlated with different pathways including inflammation (coefficient of determination (R2) 0.30; p<0.001), nutrition (R2 0.20; p<0.001) and blood diseases (R2 0.30; p<0.001 The association was eliminated after including different biological pathways into the models with the fully adjusted regression model showing an OR of 1.02 (95%CI 0.93-1.12; p = 0.664) for the association of RDW and mortality. Similar effects were found for other outcomes including intensive care unit admission and hospital readmission. CONCLUSION Our data suggests that RDW is a strong surrogate marker of mortality in unselected medical inpatients with most of the prognostic information being explained by other disease factors. The strong correlation of RDW and different biological pathways such as chronic inflammation, malnutrition and blood disease suggest that RDW may be viewed as an unspecific and general "chronic disease prognostic marker".