The balance between pro- and anti-inflammatory cytokines is associated with platelet aggregability in acute coronary syndrome patients

A. M. Gori, F. Cesari, R. Marcucci, B. Giusti, R. Paniccia, E. Antonucci, G. F. Gensini, R. Abbate

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Residual platelet reactivity (RPR) on antiplatelet therapy in ischemic heart disease patients is associated with adverse events. Clinical, cellular and pharmacogenetic factors may account for the variable response to antiplatelet treatment. Objective: We sought to explore the interplay of multiple pro-inflammatory and anti-inflammatory cytokines with platelet function in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) on dual antiplatelet therapy. Methods: In 208 ACS patients undergoing PCI on dual antiplatelet therapy we measured platelet function by platelet aggregation with two agonists [1 mM arachidonic acid (AA) and 10 μM ADP]. IL-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-12, IP-10, IFN-γ, MCP-1, MIP-1α, MIP-1β, TNF-α, and VEGF levels were determined by using the Bio-Plex cytokine assay (Bio-Rad Laboratories Inc., Hercules, CA, USA). We defined patients with RPR those with platelet aggregation by AA ≥20% and/or ADP (10 μmol) ≥70%. Results: We documented a significant association between IP-10, IFN-γ, IL-4 and RPR by both AA- and ADP-induced platelet aggregation after adjustment for age, sex, cardiovascular risk factors, ejection fraction, BMI, vWF and CRP. Patients with pro-inflammatory cytokines not compensated by anti-inflammatory cytokines had higher risk of RPR by both AA and ADP (AA: OR = 3.85, 95% CI 1.52-9.74; ADP: OR = 2.49, 95% CI 1.33-4.68) with respect to patients with balanced anti-/pro-inflammatory cytokines. Patients with anti-inflammatory response overwhelming pro-inflammatory response have lower risk of RPR (AA: OR = 0.55, 95% CI 0.28-1.06; ADP: OR = 0.47, 95% CI 0.26-0.87). Conclusion: Our study provides new insights into the interplay of anti-/pro-inflammatory cytokines with platelet hyper-reactivity in high-risk patients.

Original languageEnglish
Pages (from-to)255-262
Number of pages8
JournalAtherosclerosis
Volume202
Issue number1
DOIs
Publication statusPublished - Jan 2009

Keywords

  • Anti-inflammatory cyto-chemokines
  • C-reactive protein
  • Inflammation
  • Pro-inflammatory cyto-chemokines
  • Residual platelet reactivity
  • Von Willebrand factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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