Lack of association between serum paraoxonase-1 activity and residual platelet aggregation during dual anti-platelet therapy.

Abstract

High residual platelet aggregability during thienopyridine treatment occurs because of low levels of the active drug metabolite, and is associated with an increased rate of major adverse cardiovascular events. Recent findings suggest that paraoxonase-1 (PON1) is a major determinant for clopidogrel efficacy. The aim of this study was to assess the impact of serum PON1 activity on platelet aggregability in thienopyridine-treated patients. In 72 patients receiving treatment with aspirin and ticlopidine after acute coronary syndrome, various laboratory data including the formation of platelet aggregations induced by agonists were compared with serum PON1 activities, measured as paraoxonase and homocysteine thiolactone hydrolase (HTLase). Serum paraoxonase activity was significantly associated with HTLase activity (R=0.4487, P<0.0001). These PON1 activities were not correlated with any parameters for platelet aggregation, hypertension, sleep apnea, and diabetes mellitus. In contrast, serum PON1 activities seemed to be involved in cardiac function, with brain natriuretic peptide and ejection fraction being significantly correlated with serum HTLase activity (R=-0.2767, P=0.0214) and paraoxonase activity (R=0.2558, P=0.0339), respectively. Paraoxonase activity also demonstrated a significant association with increased levels of ankle-brachial index (R=0.267, P=0.0255). Serum PON1 activities did not influence platelet aggregability during treatment with thienopyridine. However, they might modulate cardiac function after acute coronary syndrome and progression of atherosclerosis.

• Authors: Tsukasa Ohmori, Yuichiro Yano, Asuka Sakata, Tomokazu Ikemoto, Masahisa Shimpo, Seiji Madoiwa, Takaaki Katsuki, Jun Mimuro, Kazuyuki Shimada, Kazuomi Kario, Yoichi Sakata
• Journal: Thrombosis research (Thromb Res) Vol. 129 Issue 4 Pg. e36-40 (Apr 2012) ISSN: 1879-2472 [Electronic] United States
• PMID: 22115701 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Platelet Aggregation Inhibitors
• Pyridines
• thienopyridine
• Aryldialkylphosphatase
• PON1 protein, human

Topics

• Acute Coronary Syndrome (drug therapy, physiopathology)
• Aryldialkylphosphatase (blood)
• Enzyme Activation (drug effects)
• Female
• Humans
• Male
• Middle Aged
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (administration & dosage)
• Pyridines (administration & dosage)
• Statistics as Topic
• Treatment Outcome