title: Leukocyte count is associated with increased platelet reactivity and diminished response to aspirin in healthy individuals with a family history of coronary artery disease.
abstract: BACKGROUND
  Markers of systemic inflammation, including blood leukocyte count, are associated with increased cardiovascular risk, but the mechanisms underlying this association are unclear. Leukocytes may promote platelet reactivity and thrombus formation, providing a basis for increased risk, but a relation between leukocyte count and platelet function has not been studied.
  
  
  METHODS
  We evaluated the relation of blood leukocyte count, C-reactive protein (CRP), and interleukin-6 (IL-6) to platelet aggregation to collagen, ADP and arachidonic acid, and to urinary excretion of 11-dehydro thromboxane B2. Studies were conducted in 1600 individuals (45.0+/-12.9 years, 42.7% male) at risk for coronary artery disease (CAD) before and after low dose aspirin.
  
  
  RESULTS
  At baseline, platelet reactivity increased with increasing quartile of leukocyte count (median counts for each quartile were normal) for all measures of platelet function (P<0.0001). These relations were unchanged by aspirin. The relation between leukocyte count and each measure of platelet reactivity remained significant (P<0.05) after multivariable adjustment for CRP, IL-6, cardiac risk factors, hematologic variables, and platelet thromboxane production. CRP and IL-6 were independently associated with few measures of platelet reactivity.
  
  
  CONCLUSIONS
  Increasing quartile of leukocyte count, even within the normal range, is associated with increasing platelet reactivity in individuals at risk for CAD. This relationship is not altered by aspirin and is independent of inflammatory markers and platelet thromboxane production. Additional studies are needed to determine the mechanism(s) for this association and therapies to reduce cardiovascular risk in patients with elevated leukocyte counts.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Division of Cardiac Surgical Intensive Care, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. nfaraday@jhmi.edu
authors.forename: Nauder
authors.initials: N
authors.lastname: Faraday
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Yanek
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Vaidya
authors.forename: Brian
authors.initials: B
authors.lastname: Kral
authors.forename: Rehan
authors.initials: R
authors.lastname: Qayyum
authors.forename: J Enrique
authors.initials: JE
authors.lastname: Herrera-Galeano
authors.forename: Taryn F
authors.initials: TF
authors.lastname: Moy
authors.forename: Diane M
authors.initials: DM
authors.lastname: Becker
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Becker
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage*; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood*; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D001241:Aspirin