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Similar Inflammatory Biomarkers Reflect Different Platelet Reactivity in Percutaneous Coronary Intervention Patients Treated With Clopidogrel: A Large-Sample Study From China.

ABSTRACT: Background: Platelet reactivity is closely associated with adverse events in percutaneous coronary intervention (PCI) patients. Inflammation plays a crucial role in the development of coronary heart disease (CHD). Aim: To investigate the association of inflammatory biomarkers such as leukocyte count and high-sensitivity C reactive proteins (hs-CRP) with platelet reactivity in PCI patients treated with clopidogrel. Method: We examined 10,724 consecutive PCI patients in Fuwai hospital from January 2013 to December 2013. High on-treatment platelet reactivity (HTPR) was defined as adenosine diphosphate (ADP)-induced platelet maximum amplitude [MA(ADP)] of thromboelastogram (TEG) > 47 mm, and low on-treatment platelet reactivity (LTPR) MA(ADP) < 31 mm. Results: Finally, 6,772 PCI patients treated with clopidogrel who had the results of postoperative TEG were enrolled. Among them, 2,070 (30.57%) presented HTPR and 2,568 (37.92%) presented LTPR. As for LTPR, multivariate logistic regression showed that leukocyte count (OR: 1.153, 95% CI 1.117-1.191) and hs-CRP (OR: 0.920, 95% CI 0.905-0.936) were independent predictors, along with diabetes mellites, hemoglobin, platelet count and glucose. As for HTPR, multivariate logistic regression showed that leukocyte count (OR: 0.885, 95% CI 0.854-0.917) and hs-CRP (OR: 1.094, 95% CI 1.077-1.112) were independent predictors, along with sex, hemoglobin, platelet count and glucose. Conclusions: This was the first large real-world study reporting that both leukocyte count and hs-CRP were the independent factors for platelet reactivity in PCI populations treated with clopidogrel, among which higher leukocyte count was associated with more LTPR while higher hs-CRP was associated with more HTPR, providing new insights on individualized antiplatelet therapy.

SUBMITTER: Li J

PROVIDER: S-EPMC8521006 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Similar Inflammatory Biomarkers Reflect Different Platelet Reactivity in Percutaneous Coronary Intervention Patients Treated With Clopidogrel: A Large-Sample Study From China.

Li Jiawen J Yuan Deshan D Jiang Lin L Tang Xiaofang X Xu Jingjing J Song Ying Y Chen Jue J Qiao Shubin S Yang Yuejin Y Gao Runlin R Xu Bo B Yuan Jinqing J Zhao Xueyan X

Frontiers in cardiovascular medicine 20211004

Background: Platelet reactivity is closely associated with adverse events in percutaneous coronary intervention (PCI) patients. Inflammation plays a crucial role in the development of coronary heart disease (CHD). Aim: To investigate the association of inflammatory biomarkers such as leukocyte count and high-sensitivity C reactive proteins (hs-CRP) with platelet reactivity in PCI patients treated with clopidogrel. Method: We examined 10,724 consecutive PCI patients in Fuwai ...[more]

PMID: 34671655

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Project description:BackgroundHigh platelet reactivity (HPR) and low platelet reactivity (LPR) are associated with an increased risk of ischemic/bleeding events in patients undergoing percutaneous coronary intervention (PCI). The role platelet miRNAs carry out in platelet reactivity regulation is largely unknown.MethodsIn this study, we profiled the expression pattern of platelet miRNA in patients undergoing PCI with HPR (n=4) and LPR (n=4) by miRNA microarray screening. The candidate miRNAs were further validated in a larger sample of 17 LPR and 22 HPR patients by quantitative reverse-transcription polymerase chain reaction (RT-qPCR), and miR-15b was found differentially expressed. MiR-15b mimic and inhibitor were transfected into MEG-01 cells, then Bcl-2 protein expression and cell apoptosis were assessed. The relationship between platelet reactivity and platelet apoptosis was further evaluated. ABT-737, a Bcl-2 inhibitor was used to induce platelet apoptosis in PCI patients in vitro, and the influence of enhanced platelet apoptosis on platelet reactivity was explored.ResultsTwo miRNAs were found to be differentially expressed in patients with LPR and HPR using microarray system. Furthermore, the expression of miR-15b, a miRNA known to induce cell apoptosis via targeting of Bcl-2, was confirmed by RT-qPCR (P=0.020) to be 1.4× higher in the platelets of LPR patients than in those of HPR patients. Overexpression of miR-15b was demonstrated to suppress Bcl-2 protein expression and enhance cell apoptosis in a megakaryocyte cell line (MEG-01). The platelets of LPR patients expressed lower levels of Bcl-2 protein than those of HPR patients, and an inverse relationship between platelet reactivity and platelet apoptosis was observed among 44 patients who underwent PCI. Inducing platelet apoptosis in PCI patients in vitro, we observed that their platelet reactivity was decreased in a dose-dependent manner.ConclusionsThrough the promotion of platelet apoptosis, platelet miR-15b negatively regulates platelet reactivity in patients undergoing PCI. Platelet apoptosis may represent a novel antiplatelet target for overcoming HPR in PCI treatment.

Dataset Information

Similar Inflammatory Biomarkers Reflect Different Platelet Reactivity in Percutaneous Coronary Intervention Patients Treated With Clopidogrel: A Large-Sample Study From China.

Publications

Similar Inflammatory Biomarkers Reflect Different Platelet Reactivity in Percutaneous Coronary Intervention Patients Treated With Clopidogrel: A Large-Sample Study From China.

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