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Todd S. Perlstein, MD, MMSc; Jennifer Weuve, ScD; Marc A. Pfeffer, MD, PhD; Joshua A. Beckman, MD, MSc

Arch Intern Med. 2009;169(6):588-594.

Background  Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity (eg, anisocytosis) that is largely overlooked, is a newly recognized risk marker in patients with established cardiovascular disease (CVD). It is unknown whether RDW is associated with mortality in the general population or whether this association is specific to CVD.

Methods  We examined the association of RDW with all-cause mortality and with CVD, cancer, and chronic lower respiratory tract disease mortality in 15 852 adult participants in the Third National Health and Nutrition Examination Survey (1988-1994), a nationally representative sample of the US population. Mortality status was obtained by matching to the National Death Index, with follow-up through December 31, 2000.

Results  Estimated mortality rates increased 5-fold from the lowest to the highest quintile of RDW after accounting for age and 2-fold after multivariable adjustment (P_trend < .001 for each). A 1–SD increment in RDW (0.98%) was associated with a 23% greater risk of all-cause mortality (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.18-1.28) after multivariable adjustment. The RDW was also associated with risk of death due to CVD (HR, 1.22; 95% CI, 1.14-1.31), cancer (1.28; 1.21-1.36), and chronic lower respiratory tract disease (1.32; 1.17-1.49).

Conclusions  Higher RDW is associated with increased mortality risk in this large, community-based sample, an association not specific to CVD. Study of anisocytosis may, therefore, yield novel pathophysiologic insights, and measurement of RDW may contribute to risk assessment.

Author Affiliations: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School (Drs Perlstein, Pfeffer, and Beckman), and Department of Environmental and Occupational Medicine and Epidemiology, Harvard School of Public Health (Dr Weuve), Boston, Massachusetts.

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