The relationship between fractional flow reserve, platelet reactivity and platelet leukocyte complexes in stable coronary artery disease

PLoS One. 2013 Dec 31;8(12):e83198. doi: 10.1371/journal.pone.0083198. eCollection 2013.

Abstract

Background: The presence of stenoses that significantly impair blood flow and cause myocardial ischemia negatively affects prognosis of patients with stable coronary artery disease. Altered platelet reactivity has been associated with impaired prognosis of stable coronary artery disease. Platelets are activated and form complexes with leukocytes in response to microshear gradients caused by friction forces on the arterial wall or flow separation. We hypothesized that the presence of significantly flow-limiting stenoses is associated with altered platelet reactivity and formation of platelet-leukocyte complexes.

Methods: One hundred patients with stable angina were studied. Hemodynamic significance of all coronary stenoses was assessed with Fractional Flow Reserve (FFR). Patients were classified FFR-positive (at least one lesion with FFR≤0.75) or FFR-negative (all lesions FFR>0.80). Whole blood samples were stimulated with increasing concentrations of ADP, TRAP, CRP and Iloprost with substimulatory ADP. Expression of P-selectin as platelet activation marker and platelet-leukocyte complexes were measured by flowcytometry. Patients were stratified on clopidogrel use. FFR positive and negative patient groups were compared on platelet reactivity and platelet-leukocyte complexes.

Results: Platelet reactivity between FFR-positive patients and FFR-negative patients did not differ. A significantly lower percentage of circulating platelet-neutrophil complexes in FFR-positive patients and a similar non-significant decrease in percentage of circulating platelet-monocyte complexes in FFR-positive patients was observed.

Conclusion: The presence of hemodynamically significant coronary stenoses does not alter platelet reactivity but is associated with reduced platelet-neutrophil complexes in peripheral blood of patients with stable coronary artery disease.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Platelets / pathology
  • Clopidogrel
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / physiopathology*
  • Coronary Stenosis / blood
  • Coronary Stenosis / drug therapy
  • Coronary Stenosis / physiopathology
  • Female
  • Fractional Flow Reserve, Myocardial*
  • Humans
  • Leukocytes / pathology
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / drug therapy
  • Myocardial Ischemia / physiopathology
  • Platelet Activation*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prognosis
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine

Grants and funding

This research was performed within the framework of CTMM, the Center for Translational Molecular Medicine (www.ctmm.nl), project CIRCULATING CELLS (grant 01C-102), and supported by the Dutch Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.