Bigalke Boris, Geisler Tobias, Stellos Konstantinos, Langer Harald, Daub Karin, Kremmer Elisabeth, Seizer Peter, May Andreas E, Lindemann Stephan, Gawaz Meinrad
Medizinische Klinik, Klinik für Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Tübingen, Germany.
Am Heart J. 2008 Jul;156(1):193-200. doi: 10.1016/j.ahj.2008.02.010. Epub 2008 Apr 23.
Platelet collagen receptor glycoprotein VI (GPVI) plays a critical role in acute coronary thrombosis. This prospective study examined the predictive value of GPVI for acute coronary syndromes (ACS) in a large consecutive group of patients with symptomatic coronary artery disease to identify the high-risk cohort with imminent coronary events.
We evaluated 1,003 patients with symptomatic coronary artery disease, verified by coronary angiography, and determined the surface expression of GPVI using flow cytometry. In a subgroup of 471 patients, who were treated with aspirin plus clopidogrel for coronary stenting, adenosine disphosphate (20 micromol/L)-induced platelet aggregation was evaluated.
Patients with ACS (n = 485) showed a significantly enhanced GPVI expression compared to patients with stable angina pectoris (SAP; n = 518) (mean fluorescence intensity for ACS 19.8 +/- 5.9; SAP 18.7 +/- 8.5, P = .01). Patients with elevated GPVI levels on admission (GPVI cutoff value > or =18.6 mean fluorescence intensity) had a 1.4-fold relative risk for ACS. Logistic regression analysis showed that an elevated platelet GPVI level may indicate ACS independent of biomarkers of myocardial necrosis including troponin, creatine kinase, and creatine kinase-MB. Patients with increased platelet activation (GPVI expression level > or =18.6) showed significant enhanced residual platelet aggregation despite dual antiplatelet therapy compared to patients with low GPVI levels (P = .028).
Surface expression of GPVI is enhanced in patients with ACS and indicates an imminent acute coronary event before irreversible myocardial necrosis is evident. High GPVI levels are associated with increased residual platelet aggregation despite antiplatelet therapy. Therefore, GPVI is useful to identify the subgroup of patients with a high risk for coronary stent thrombosis and thromboischemic events.
血小板胶原受体糖蛋白VI(GPVI)在急性冠状动脉血栓形成中起关键作用。这项前瞻性研究在一大组连续性有症状冠状动脉疾病患者中,检验了GPVI对急性冠状动脉综合征(ACS)的预测价值,以识别即将发生冠状动脉事件的高危队列。
我们评估了1003例经冠状动脉造影证实有症状冠状动脉疾病的患者,并使用流式细胞术测定GPVI的表面表达。在471例接受阿司匹林加氯吡格雷进行冠状动脉支架置入治疗的患者亚组中,评估了二磷酸腺苷(20微摩尔/升)诱导的血小板聚集情况。
与稳定型心绞痛(SAP;n = 518)患者相比,ACS患者(n = 485)的GPVI表达显著增强(ACS的平均荧光强度为19.8±5.9;SAP为18.7±8.5,P = 0.01)。入院时GPVI水平升高(GPVI临界值≥18.6平均荧光强度)的患者发生ACS的相对风险为1.4倍。逻辑回归分析表明,血小板GPVI水平升高可能提示ACS,独立于包括肌钙蛋白、肌酸激酶和肌酸激酶同工酶MB在内的心肌坏死生物标志物。与低GPVI水平的患者相比,血小板活化增加(GPVI表达水平≥18.6)的患者尽管接受了双联抗血小板治疗,仍显示残余血小板聚集显著增强(P = 0.028)。
ACS患者的GPVI表面表达增强,且在不可逆心肌坏死明显之前提示即将发生急性冠状动脉事件。尽管进行了抗血小板治疗,但高GPVI水平与残余血小板聚集增加相关。因此,GPVI有助于识别冠状动脉支架血栓形成和血栓缺血事件高危患者亚组。