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J Am Coll Cardiol, 2004; 44:1945-1956, doi:10.1016/j.jacc.2004.07.056
© 2004 by the American College of Cardiology Foundation
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STATE-OF-THE-ART PAPER

Leukocyte count and coronary heart disease

Implications for risk assessment

Mohammad Madjid, MD*,{dagger},*, Imran Awan, MD*,{dagger}, James T. Willerson, MD*,{dagger} and S. Ward Casscells, MD*,{dagger},{ddagger}

* University of Texas–Houston Health Science Center, Houston, Texas
{dagger} Texas Heart Institute, Houston, Texas
{ddagger} President Bush Center for Cardiovascular Health at Memorial Hermann Hospital, Houston, Texas

Manuscript received March 4, 2004; revised manuscript received July 10, 2004, accepted July 13, 2004.

* Reprint requests and correspondence: Dr. Mohammad Madjid, 6431 Fannin, MSB 1.260, Houston, Texas 77030 (Email: Mohammad.Madjid{at}uth.tmc.edu).

Inflammation is a key feature of atherosclerosis and its clinical manifestations. The leukocyte count is a marker of inflammation that is widely available in clinical practice. This paper reviews the available epidemiologic evidence for a relationship between the leukocyte count and coronary heart disease (CHD). Numerous epidemiologic and clinical studies have shown leukocytosis to be an independent predictor of future cardiovascular events, both in healthy individuals free of CHD at baseline and in patients with stable angina, unstable angina, or a history of myocardial infarction. This relationship has been observed in prospective and retrospective cohort studies, as well as in case-control studies. It is strong, consistent, temporal, dose-dependent, and biologically plausible. The relationship persists after adjustment for multiple CHD risk factors, including smoking. Elevated differential cell counts, including eosinophil, neutrophil, and monocyte counts, also predict the future incidence of CHD. Leukocytosis affects CHD through multiple pathologic mechanisms that mediate inflammation, cause proteolytic and oxidative damage to the endothelial cells, plug the microvasculature, induce hypercoagulability, and promote infarct expansion. In summary, leukocytosis has been consistently shown to be an independent risk factor and prognostic indicator of future cardiovascular outcomes, regardless of disease status. The leukocyte count is inexpensive, reliable, easy to interpret, and ordered routinely in inpatient and outpatient settings. However, its diagnostic and prognostic utility in CHD is widely unappreciated. Further studies are needed to assess the true impact of leukocytosis on CHD, compare it with other inflammatory markers such as C-reactive protein and lipoprotein phospholipase A2 levels, and promote its use in CHD prediction.

Abbreviations and Acronyms
  BMI = body mass index
  CAD = coronary artery disease
  CHD = coronary heart disease
  CK = creatine kinase
  CRP = C-reactive protein
  CVD = cardiovascular disease
  IL = interleukin
  MI = myocardial infarction
  UA = unstable angina
  WBC = white blood cell




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