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

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

doi:10.1016/j.atherosclerosis.2008.04.001

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Volume 202, Issue 1 , Pages 255-262, January 2009

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

A.M. Gori
- Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy
- Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy
- Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
- Corresponding author at: Thrombosis Center, Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. Tel.: +39 0557949420; fax: +39 0557949418.
F. Cesari
- Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy
- Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy
R. Marcucci
- Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy
- Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy
- Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
B. Giusti
- Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy
- Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy
- Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
R. Paniccia
- Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy
- Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy
- Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
E. Antonucci
- Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy
- Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy
G.F. Gensini
- Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy
- Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy
- Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
- Centro S. Maria agli Ulivi, Fondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta, Florence, Italy
R. Abbate
- Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy
- Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy
- Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

Received 27 October 2007; received in revised form 21 March 2008; accepted 2 April 2008. published online 20 May 2008.

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 [1mM arachidonic acid (AA) and 10μM 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 (10μmol) ≥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).