Markuszewski Leszek, Rosiak Marcin, Golanski Jacek, Rysz Jacek, Spychalska Magdalena, Watala Cezary
Department of Interventional Cardiology, Cardiodiabetology and Cardiac Rehabilitation, Medical University of Lodz, University Hospital no. 2, Lodz, Poland.
Basic Clin Pharmacol Toxicol. 2006 May;98(5):503-9. doi: 10.1111/j.1742-7843.2006.pto_343.x.
The study was designed to assess blood platelet sensitivity to acetylsalicylic acid and its associations with dyslipidaemia and inflammation in coronary artery disease patients. Platelet non-responsiveness to aspirin is associated with an increased risk of serious cardiovascular events. Several environmental and hereditary factors are reportedly involved in sub-optimal acetylsalicylic acid response. Forty-five coronary artery disease patients and 45 non-coronary artery disease controls received acetylsalicylic acid at a daily dose of 75-150 mg. Controls were examined twice: on the day of entering the study and 10 days later. Urinary 11-dehydrothromboxane B2 was assessed as the marker of platelet thromboxane generation. Aggregation was studied in platelet-rich plasma using turbidimetric aggregometry with collagen and arachidonic acid. Fifty to seventy percent of coronary artery disease patients showed an extent of collagen-induced aggregation above the upper quartile of the reference range compared with 8-15% in controls (P<0.003). For arachidonic acid-activated aggregation these proportions were 45-50% in coronary artery disease versus 7% in controls (P<0.007). In coronary artery disease patients, the acetylsalicylic acid-mediated platelet inhibition positively correlated with increased triglycerides (in arachidonic acid-stimulated platelets, r=0.30, P=0.0018), total cholesterol (r=0.33, P<0.0001 in coll and arachidonic acid-activated platelets) and elevated serum C-reactive protein (CRP) (r=0.27, P=0.0024). In coronary artery disease patients urine 11-dehydrothromboxane B2 concentrations were significantly increased compared to controls after 10 day acetylsalicylic acid intake (563; 313-728 pg/mg creatinine versus 321; 246-488 pg/mg creatinine, P=0.04). The incidence of suboptimal acetylsalicylic acid response incidence was more common in patients with coronary artery disease. Acetylsalicylic acid inhibition of blood platelet reactivity and thromboxane generation was less effective in these patients. Dyslipidaemia and chronic inflammatory states may promote suboptimal acetylsalicylic acid response in coronary artery disease patients.
本研究旨在评估冠状动脉疾病患者血小板对乙酰水杨酸的敏感性及其与血脂异常和炎症的关联。血小板对阿司匹林无反应与严重心血管事件风险增加相关。据报道，几种环境和遗传因素与乙酰水杨酸反应欠佳有关。45例冠状动脉疾病患者和45例非冠状动脉疾病对照者接受每日剂量75 - 150毫克的乙酰水杨酸治疗。对照者接受两次检查：进入研究当天和10天后。尿11 - 脱氢血栓素B2作为血小板血栓素生成的标志物进行评估。使用比浊法聚集测定仪，在富含血小板的血浆中研究胶原和花生四烯酸诱导的聚集情况。50%至70%的冠状动脉疾病患者显示胶原诱导的聚集程度高于参考范围的上四分位数，而对照者为8% - 15%（P < 0.003）。对于花生四烯酸激活的聚集，冠状动脉疾病患者的这一比例为45% - 50%，对照者为7%（P < 0.007）。在冠状动脉疾病患者中，乙酰水杨酸介导的血小板抑制与甘油三酯升高呈正相关（在花生四烯酸刺激的血小板中，r = 0.30，P = 0.0018）、总胆固醇升高（r = 0.33，在胶原和花生四烯酸激活的血小板中P < 0.0001）以及血清C反应蛋白（CRP）升高（r = 0.27，P = 0.0024）。在冠状动脉疾病患者中，摄入乙酰水杨酸10天后，尿11 - 脱氢血栓素B2浓度与对照者相比显著升高（563；313 - 728 pg/mg肌酐 对比 321；246 - 488 pg/mg肌酐，P = 0.04）。冠状动脉疾病患者中乙酰水杨酸反应欠佳的发生率更高。在这些患者中，乙酰水杨酸对血小板反应性和血栓素生成的抑制效果较差。血脂异常和慢性炎症状态可能促使冠状动脉疾病患者出现乙酰水杨酸反应欠佳的情况。
