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Background  While the mortality rate is declining in the United States, the life expectancy gap among different population groups suggests a need to identify biomarkers to improve early identification of individuals at risk. Red cell distribution width (RDW), a measure of anisocytosis, is an emerging biomarker of chronic disease morbidity and mortality, particularly in the elderly. However, little is known about its association with mortality risk in younger adults. The objectives of this study were to investigate the association between RDW and overall and cause-specific mortality risk, and to identify novel determinants of RDW level.    Methods  We used prospectively collected data from the Healthy Aging in Neighborhoods of Diversity across the Life Span study conducted in Baltimore, Maryland. At baseline (2004–2009), the study recruited 3720 African American and white men and women aged 30–64 years. Participants provided peripheral venous blood for RDW measurement as part of complete blood count, and genotyping. Mortality status was ascertained using the National Death Index database through December 31, 2013. Multivariable adjusted Cox proportional hazards regression models were fitted to assess mortality risk, and multiple linear regression models to identify determinants of RDW level.    Results  Participants’ mean age was 48.1 (9.2) years. Of 2726 participants included in the present analyses, 57% were African Americans, and 56% were women. After 18,424 person-years of follow-up time, there were 226 deaths, and the leading cause of death were cardiovascular diseases (31.9%). Participants in the highest quartile of RDW had a 1.73-fold increased all-cause mortality risk (highest quartile vs. lowest quartile, multivariable adjusted hazard ratio = 1.73, 95% confidence interval: 1.10–2.74, p-trend = 0.006). This effect was significantly modified by body mass index (p-interaction = 0.004). Similar risk was observed for cardiovascular disease-specific mortality. Independent of body mass index, waist-hip ratio and illicit drug use were significantly associated with RDW.    Conclusions  Elevated RDW was associated with a substantial risk of all-cause and cardiovascular disease-specific mortalities that was modified by body mass index. Central obesity and illicit drug use influence RDW level. In vulnerable populations at-risk for health disparities, RDW could provide a useful and inexpensive biomarker of mortality.    Electronic supplementary material  The online version of this article (doi:10.1186/s12967-017-1313-6) contains supplementary material, which is available to authorized users.

journal of translational medicine

Association of red cell distribution width with all-cause and cardiovascular-specific mortality in African American and white adults: a prospective cohort study