Division of Cardiovascular Medicine, University of California-San Diego Sulpizio Cardiovascular Center, La Jolla, California 92037, USA.
J Am Coll Cardiol. 2013 Jan 8;61(1):23-34. doi: 10.1016/j.jacc.2012.09.037.
This study was undertaken to determine the roles of serum fibrinogen and residual platelet reactivity after clopidogrel pre-treatment on ischemic events after elective percutaneous coronary intervention (PCI).
Both elevated serum fibrinogen and high platelet reactivity with thienopyridines are associated with ischemic cardiovascular events. Elevated fibrinogen also contributes to high on-clopidogrel platelet reactivity. It is unknown whether fibrinogen and residual platelet reactivity are associated with adverse cardiovascular events through independent or interactive effects.
A total of 189 patients undergoing elective PCI with clopidogrel pre-treatment (75 mg daily for ≥7 days or a 600-mg bolus ≥12 h before recruitment) were prospectively enrolled. Baseline fibrinogen and platelet function using the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) were obtained. Markers of ischemic myocardial injury were measured every 8 h after PCI.
Incidence of troponin-defined periprocedural myocardial infarction (PPMI) (troponin I/T >3× upper limit of normal) was 13.9% and associated with elevated fibrinogen (363.1 ± 131.0 mg/dl vs. 309.1 ± 99.6 mg/dl; p = 0.017), higher age (68.2 ± 10.1 years vs. 63.0 ± 11.8 years; p = 0.040), and elevated platelet count. Fibrinogen level and age remained independently associated with PPMI following multiple variable and interaction testing. The incidence of creatine kinase-myocardial band (CK-MB)-defined PPMI (CK-MB >3× upper limit of normal) was 5.8% and associated with elevated fibrinogen (403.4 ± 128.0 mg/dl vs. 313.5 ± 104.6 mg/dl; p = 0.007). Platelet reactivity measurements were not associated with PPMI by either definition. Fibrinogen ≥345 mg/dl was significantly associated with both CK-MB-defined (p = 0.026) and troponin I/T-defined PPMI (p = 0.036). Fibrinogen effects were most prominent in the absence of systemic inflammation (C-reactive protein ≤0.5 mg/dl).
Elevated fibrinogen is independently associated with the risk of ischemic myocardial injury following elective PCI with clopidogrel pre-treatment regardless of platelet reactivity as measured by the VerifyNow assay.
本研究旨在确定氯吡格雷预处理后血清纤维蛋白原和残余血小板反应性在择期经皮冠状动脉介入治疗（PCI）后缺血事件中的作用。
升高的血清纤维蛋白原和噻吩吡啶的高血小板反应性均与缺血性心血管事件相关。升高的纤维蛋白原也导致氯吡格雷治疗后血小板高反应性。尚不清楚纤维蛋白原和残余血小板反应性是否通过独立或相互作用与不良心血管事件相关。
前瞻性纳入 189 例行择期 PCI 并接受氯吡格雷预处理的患者（每日 75 mg 氯吡格雷治疗≥7 天或在入组前 12 小时给予 600 mg 负荷剂量）。测定基线纤维蛋白原和血小板功能，采用 VerifyNow P2Y12 检测（Accumetrics，圣地亚哥，加利福尼亚州）。PCI 后每 8 小时测定缺血性心肌损伤标志物。
肌钙蛋白定义的围术期心肌梗死（PPMI）（肌钙蛋白 I/T>3×正常值上限）发生率为 13.9%，与纤维蛋白原升高（363.1±131.0 mg/dl 比 309.1±99.6 mg/dl；p=0.017）、高龄（68.2±10.1 岁比 63.0±11.8 岁；p=0.040）和血小板计数升高相关。经多变量和交互检验，纤维蛋白原水平和年龄与 PPMI 仍独立相关。肌酸激酶同工酶-肌红蛋白带（CK-MB）定义的 PPMI（CK-MB>3×正常值上限）发生率为 5.8%，与纤维蛋白原升高相关（403.4±128.0 mg/dl 比 313.5±104.6 mg/dl；p=0.007）。两种定义的 PPMI 均与血小板反应性无关。纤维蛋白原≥345 mg/dl 与 CK-MB 定义的（p=0.026）和肌钙蛋白 I/T 定义的 PPMI（p=0.036）显著相关。在没有全身炎症（C 反应蛋白≤0.5 mg/dl）的情况下，纤维蛋白原的作用最为明显。
氯吡格雷预处理后行择期 PCI 时，无论使用 VerifyNow 检测测定的血小板反应性如何，升高的纤维蛋白原均与缺血性心肌损伤的风险独立相关。
