TY - JOUR
T1 - Lack of association between serum paraoxonase-1 activity and residual platelet aggregation during dual anti-platelet therapy
AU - Ohmori, Tsukasa
AU - Yano, Yuichiro
AU - Sakata, Asuka
AU - Ikemoto, Tomokazu
AU - Shimpo, Masahisa
AU - Madoiwa, Seiji
AU - Katsuki, Takaaki
AU - Mimuro, Jun
AU - Shimada, Kazuyuki
AU - Kario, Kazuomi
AU - Sakata, Yoichi
N1 - Funding Information:
T.O. has received financial support from Daiichi Sankyo. The other authors declare that they have no competing interest.
Funding Information:
We would like to acknowledge Dr. Y. Yatomi (The University of Tokyo) for very helpful discussions. The authors are grateful for the hard work of the Coronary Care Unit staff in patient recruitment and management. We also thank N. Matsumoto and M. Ito for their excellent technical assistance. This study was supported by grants from the Support Program for Strategic Research Infrastructure from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - antiplatelet agent
KW - coronary syndrome
KW - platelet pharmacology
UR - http://www.scopus.com/inward/record.url?scp=84858333716&partnerID=8YFLogxK
U2 - 10.1016/j.thromres.2011.10.033
DO - 10.1016/j.thromres.2011.10.033
M3 - Article
C2 - 22115701
AN - SCOPUS:84858333716
SN - 0049-3848
VL - 129
SP - e36-e40
JO - Thrombosis Research
JF - Thrombosis Research
IS - 4
ER -