Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine.
Department of Cardiology, Osaka City General Hospital.
J Atheroscler Thromb. 2018 Nov 1;25(11):1105-1117. doi: 10.5551/jat.43166. Epub 2018 Mar 28.
Neopterin is an activation marker for monocytes/macrophages. We prospectively investigated the predictive value of plasma neopterin levels on 2-year and long-term cardiovascular events in patients with stable angina pectoris (SAP) undergoing coronary stent implantation.
We studied 123 consecutive patients with SAP who underwent primary coronary stenting (44 patients with bare metal stent: BMS group and 79 with drug-eluting stent: DES group). Plasma neopterin levels were measured on admission using HPLC. Moreover, one frozen coronary artery specimen after DES and three frozen coronary specimens after BMS were obtained by autopsy or endarterectomy, followed by immunohistochemical staining for neopterin.
Plasma neopterin levels were significantly higher in patients with cardiovascular events than in those without them (P<0.001). In subgroup analyses, higher levels of plasma neopterin in patients with cardiovascular events (P<0.001) and a positive correlation between neopterin levels and late lumen loss after stenting (P =0.008) were observed in the BMS group but not in the DES group (P=0.53 and P=0.17, respectively). In long-term cardiovascular events, multivariate Cox regression analysis identified the significance of the high-neopterin group as independent determinants of cardiovascular events (hazard ratio, 2.225; 95% CI, 1.283-3.857; P =0.004). Immunohistochemical staining showed abundant neopterin-positive macrophages in the neointima after BMS implantation but no neopterin-positive macrophages in the neointima after DES implantation.
These findings suggest that neopterin is associated with cardiovascular events after coronary stent implantation in patients with SAP. However, there might be a strong association between neopterin and cardiovascular events after BMS but not after DES in these patients.
血中新蝶呤是单核细胞/巨噬细胞激活的标志物。本研究前瞻性观察了血中新蝶呤水平对稳定型心绞痛(SAP)患者经皮冠状动脉支架植入术后 2 年及长期心血管事件的预测价值。
本研究入选 123 例行冠状动脉支架植入术的 SAP 患者(裸金属支架组 44 例,药物洗脱支架组 79 例)。采用 HPLC 法检测患者入院时血中新蝶呤水平。同时,对药物洗脱支架组患者术后 1 例、裸金属支架组患者术后 3 例进行尸检或内膜切除术,获取冰冻冠状动脉组织标本,行免疫组化染色检测新蝶呤。
发生心血管事件的患者血中新蝶呤水平显著高于未发生心血管事件的患者(P<0.001)。亚组分析显示,心血管事件组患者血中新蝶呤水平较高(P<0.001),且支架置入术后晚期管腔丢失与新蝶呤水平呈正相关(P=0.008),而在药物洗脱支架组则未观察到上述相关性(P=0.53 和 P=0.17)。在长期心血管事件中,多因素 Cox 回归分析显示高水平新蝶呤组是心血管事件的独立预测因子(危险比 2.225;95%可信区间 1.283-3.857;P=0.004)。免疫组化染色显示,裸金属支架组患者支架置入术后新生内膜内有大量新蝶呤阳性巨噬细胞,而药物洗脱支架组患者则无新蝶呤阳性巨噬细胞。
本研究提示,血中新蝶呤与 SAP 患者冠状动脉支架植入术后心血管事件相关。然而,在这些患者中,新蝶呤与裸金属支架后而非药物洗脱支架后心血管事件之间可能存在较强关联。