Abstract

BackgroundWhile 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.MethodsWe 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.ResultsParticipants’ 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.ConclusionsElevated 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.

Highlights

  • 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

  • In the full model adjusted for age, sex, race, poverty status, smoking status, body mass index (BMI), low density lipoprotein-cholesterol (LDL), hypertension and diabetes mellitus, participants in the highest quartile had a 73% increased risk of all-cause mortality (Table 2)

  • In the full multivariable adjusted linear regression model, Red cell distribution width (RDW) was significantly higher among AAs compared to whites [beta (b) = 0.6 (0.5, 0.8)], and current smokers compared to non-current smokers [0.3 (0.1, 0.4)], while RDW was lower among men compared to women [− 0.3 (− 0.5, − 0.2)]

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Summary

Introduction

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, in the elderly. 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. Red cell distribution width (RDW), a measure of variation in red blood cell size known as anisocytosis, is an emerging biomarker of chronic disease morbidity and mortality [1]. Elevated RDW was associated with overall and disease-specific mortality risk [6, 8,9,10,11]. Whereas genetic variants in loci including G6PD, CD36, and NOL4L have been linked with RDW level [14, 15], the interplay between environmental factors and genetic variants on RDW has not yet been investigated

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