Published online before print January 20, 2005, doi: 10.1161/01.ATV.0000156877.94472.a5
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© 2005 American Heart Association, Inc.
Special Article |
Leukocytosis and Ischemic Vascular Disease Morbidity and Mortality
Is It Time to Intervene?
From the The Rockefeller University, New York, NY.
Correspondence to Barry S. Coller, The Rockefeller University, 1230 York Ave, New York, NY 10021. E-mail collerb{at}rockefeller.edu
The association between leukocytosis and increased morbidity and mortality of ischemic vascular disease has been observed for more than half a century, and recent studies in >350 000 patients confirm the robustness of the association and the dramatically higher relative and absolute acute and chronic mortality rates in patients with high versus low leukocyte counts. Although there is reason to believe that the association is not causal (that is, that leukocytosis is simply a marker of inflammation), there is also reason to believe that the leukocytosis directly enhances acute thrombosis and chronic atherosclerosis. Leukocytosis also is associated with poor prognosis and vaso-occlusive events in patients with sickle cell disease, and experimental data suggest a direct role for leukocytes in microvascular obstruction. The only way to test whether leukocytes contribute directly to poor outcome in ischemic cardiovascular disease is to assess the effect of modifying leukocyte function or number. Because selective blockade of leukocyte integrin 
Mß2 and P-selectin have thus far been disappointing as therapeutic strategies in human cardiovascular and cerebrovascular disease, I discuss the potential risks and benefits of short-term treatment with hydroxyurea to decrease the leukocyte count in select populations of patients at the highest risk of short-term death.
This article reviews the epidemiological evidence of an association between leukocytosis and increased morbidity and mortality from ischemic vascular disease, focusing on whether the data are consistent with a causal role for leukocytes in vascular events. It then discusses whether the existing data justify selectively entering to lower the leukocyte count.
Key Words: leukocytes • neutrophils • myocardial infarction • thrombosis
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