Clopidogrel resistance response in patients with coronary artery disease and metabolic syndrome: the role of hyperglycemia and obesity.
BACKGROUND
Despite the proven benefits of clopidogrel combined aspirin therapy for coronary artery disease (CAD), CAD patients with metabolic syndrome (MS) still tend to have coronary thrombotic events. We aimed to investigate the influence of metabolic risk factors on the efficacy of clopidogrel treatment in patients with CAD undergoing percutaneous coronary intervention (PCI).


METHODS
Cohorts of 168 MS and 168 non-MS subjects with CAD identified by coronary angiography (CAG) were enrolled in our study. MS was defined by modified Adult Treatment Panel III criteria. All subjects had taken 100 mg aspirin and 75 mg clopidogrel daily for more than 1 month, and administered loading doses of 600 mg clopidogrel and 300 mg aspirin before PCI. Blood samples were taken 24 h after the loading doses of clopidogrel and aspirin. Platelet aggregation was measured using light transmittance aggregometry (LTA) and thrombelastography (TEG). Clopidogrel resistance was defined as more than 50% adenosine diphosphate (ADP) induced platelet aggregation as measured by TEG.


RESULTS
Platelet aggregation inhibition rate by ADP was significantly lower in patients with MS as measured both by TEG (55% ± 31% vs. 68% ± 32%; P < 0.001) and LTA (29% ± 23% vs. 42% ± 29%; P < 0.001). In the multivariate analysis, elderly [OR (95% CI): 1.483 (1.047-6.248); P = 0.002], obesity [OR (95% CI): 3.608 (1.241-10.488); P = 0.018], high fasting plasma glucose level [OR (95% CI): 2.717 (1.176-6.277); P = 0.019] and hyperuricemia [OR (95% CI): 2.583 (1.095-6.094); P = 0.030] were all statistically risk factors for clopidogrel resistance. CAD patients with diabetes and obesity were more likely to have clopidogrel resistance than the CAD patients without diabetes and obesity [75% (61/81) vs. 43% (67/156); P < 0.001].


CONCLUSIONS
CAD patients with MS appeared to have poorer antiplatelet response to clopidogrel compared to those without MS. Obesity, diabetes and hyperuricemia were all significantly associated with clopidogrel resistance.
Department of Gerontology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Zhao-Ke
ZK
Wu
Department of neurology, the First Provincial Hospital of Henan Province, Zhengzhou, Henan, China.
Jing-Jing
JJ
Wang
Department of Gerontology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Ting
T
Wang
Department of Gerontology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Shen-Shen
SS
Zhu
Department of Gerontology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Xi-Ling
XL
Chen
Department of Gerontology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Chao
C
Liu
Department of Cardiology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Wei-Guo
WG
Zhang
Clopidogrel resistance; Coronary artery disease; Metabolic syndrome