Jastrzebska M, Marcinowska Z, Oledzki S, Chelstowski K, Siennicka A, Klysz M, Clark J S
Department of Laboratory Diagnostics, Pomeranian Medical University, Szczecin, Poland.
Department of Cardiology, Pomeranian Medical University, Szczecin, Poland.
J Physiol Pharmacol. 2018 Aug;69(4). doi: 10.26402/jpp.2018.4.10. Epub 2018 Dec 9.
Antiplatelet therapy is considered as a standard procedure against atherosclerotic cardiovscular disease but this therapy has limited effect if resistance to acetylsalicylic acid or clopidogrel is present. Important factors associated with resistance are gender; or inflammation possibly associated with membrane microparticles (MP). It was decided to challenge the hypothesis that differential responses to dual antiplatelet therapy are conditioned by gender and/or proinflammatory status. The study involved 160 patients with stable coronary heart disease (118 men, 42 women) aged 65.2 ± 7.8 years. Patients were treated long-term with acetylsalicylic acid (ASA); plus clopidogrel starting 6 days before percutaneous coronary intervention (both 75 mg/day). Response was evaluated using platelet aggregation with either arachidonic acid (the ASPI test; predominantly for ASA response) or adenosine diphosphate (the ADP test; predominantly for clopidogrel response). MP levels were measured as follows: total (MP-total); with TF expression (MP-TF); or platelet-derived microparticles (PDMP), as well as proinflammatory parameters: C-reactive protein (CRP), leukocytes (WBC) and platelet numbers (PLT). Analysis of platelet-aggregation levels with regard to gender revealed higher aggregation in women: with resistance to ASA (ASPI test: P = 0.0383, ADP test: P = 0.0027); resistance to clopidogrel (ASPI test: P = 0.0003; ADP test: P = 0.0566) and with sensitivity to both drugs with the ADP test (P = 0.0190). In women relative to men, regardless of response, significantly higher CRP (P = 0.0012), WBC (P = 0.0244) and PLT numbers (P = 0.0001) were found. In contrast, in men significantly higher concentrations of MP-TF (P = 0.0286) and triglycerides (P = 0.0296) were found in the clopidogrel-resistant group. We conclude that women have an inferior response to dual antiplatelet therapy relative to men, possibly associated with higher platelet reactivity (especially when measured with the ADP test), with a more accentuated proinflammatory status. In contrast, among the factors supporting the resistance in men can be an elevated concentration of MP-TF which, together with the coexistence of hypertriglyceridemia, may constitute an important mechanism of resistance to clopidogrel.
抗血小板治疗被视为对抗动脉粥样硬化性心血管疾病的标准程序，但如果存在对乙酰水杨酸或氯吡格雷的抵抗，这种治疗的效果就会有限。与抵抗相关的重要因素包括性别；以及可能与膜微粒（MP）相关的炎症。研究人员决定验证这样一个假设，即对双重抗血小板治疗的不同反应是由性别和/或促炎状态决定的。该研究纳入了160例年龄为65.2±7.8岁的稳定型冠心病患者（118名男性，42名女性）。患者长期服用乙酰水杨酸（ASA）；并在经皮冠状动脉介入治疗前6天开始服用氯吡格雷（均为75毫克/天）。使用花生四烯酸诱导的血小板聚集（阿司匹林敏感性试验；主要用于评估ASA反应）或二磷酸腺苷诱导的血小板聚集（ADP试验；主要用于评估氯吡格雷反应）来评估反应情况。MP水平的测量如下：总MP（MP-总）；表达组织因子的MP（MP-TF）；或血小板衍生微粒（PDMP），以及促炎参数：C反应蛋白（CRP）、白细胞（WBC）和血小板计数（PLT）。关于性别的血小板聚集水平分析显示，女性的聚集水平更高：对ASA有抵抗（阿司匹林敏感性试验：P = 0.0383，ADP试验：P = 0.0027）；对氯吡格雷有抵抗（阿司匹林敏感性试验：P = 0.0003；ADP试验：P = 0.0566），以及在ADP试验中对两种药物敏感（P = 0.0190）。相对于男性，无论反应如何，女性的CRP（P = 0.0012）、WBC（P = 0.0244）和PLT计数（P = 0.0001）均显著更高。相比之下，在氯吡格雷抵抗组中，男性的MP-TF浓度（P = 0.0286）和甘油三酯浓度（P = 0.0296）显著更高。我们得出结论，相对于男性，女性对双重抗血小板治疗的反应较差，这可能与更高的血小板反应性（特别是用ADP试验测量时）以及更明显的促炎状态有关。相比之下，支持男性抵抗的因素可能是MP-TF浓度升高，这与高甘油三酯血症并存，可能构成对氯吡格雷抵抗的重要机制。
