Department of Cardiology, Catharina Hospital Eindhoven, Eindhoven, The Netherlands ; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
PLoS One. 2013 Dec 31;8(12):e83198. doi: 10.1371/journal.pone.0083198. eCollection 2013.
The presence of stenoses that significantly impair blood flow and cause myocardial ischemia negatively affects prognosis of patients with stable coronary artery disease. Altered platelet reactivity has been associated with impaired prognosis of stable coronary artery disease. Platelets are activated and form complexes with leukocytes in response to microshear gradients caused by friction forces on the arterial wall or flow separation. We hypothesized that the presence of significantly flow-limiting stenoses is associated with altered platelet reactivity and formation of platelet-leukocyte complexes.
One hundred patients with stable angina were studied. Hemodynamic significance of all coronary stenoses was assessed with Fractional Flow Reserve (FFR). Patients were classified FFR-positive (at least one lesion with FFR≤0.75) or FFR-negative (all lesions FFR>0.80). Whole blood samples were stimulated with increasing concentrations of ADP, TRAP, CRP and Iloprost with substimulatory ADP. Expression of P-selectin as platelet activation marker and platelet-leukocyte complexes were measured by flowcytometry. Patients were stratified on clopidogrel use. FFR positive and negative patient groups were compared on platelet reactivity and platelet-leukocyte complexes.
Platelet reactivity between FFR-positive patients and FFR-negative patients did not differ. A significantly lower percentage of circulating platelet-neutrophil complexes in FFR-positive patients and a similar non-significant decrease in percentage of circulating platelet-monocyte complexes in FFR-positive patients was observed.
The presence of hemodynamically significant coronary stenoses does not alter platelet reactivity but is associated with reduced platelet-neutrophil complexes in peripheral blood of patients with stable coronary artery disease.
严重影响血流并导致心肌缺血的狭窄会对稳定型冠心病患者的预后产生负面影响。血小板反应性改变与稳定型冠心病的预后不良有关。血小板在动脉壁上的摩擦力或流动分离产生的微切变梯度的作用下被激活并与白细胞形成复合物。我们假设,严重限制血流的狭窄的存在与改变的血小板反应性和血小板-白细胞复合物的形成有关。
研究了 100 名稳定型心绞痛患者。所有冠状动脉狭窄的血流动力学意义均采用血流储备分数(FFR)进行评估。患者分为 FFR 阳性(至少有一个 FFR≤0.75 的病变)或 FFR 阴性(所有病变 FFR>0.80)。用不同浓度的 ADP、TRAP、CRP 和 Iloprost 刺激全血样本,并用亚刺激浓度的 ADP 刺激。通过流式细胞术测量血小板活化标志物 P-选择素的表达和血小板-白细胞复合物。根据氯吡格雷的使用情况对患者进行分层。比较 FFR 阳性和阴性患者组的血小板反应性和血小板-白细胞复合物。
FFR 阳性患者和 FFR 阴性患者之间的血小板反应性没有差异。在 FFR 阳性患者中,循环血小板-中性粒细胞复合物的百分比明显降低,而在 FFR 阳性患者中,循环血小板-单核细胞复合物的百分比也有类似的非显著降低。
血流动力学意义上的冠状动脉狭窄的存在不会改变血小板反应性,但与稳定型冠心病患者外周血中血小板-中性粒细胞复合物的减少有关。