Aoyama Masayuki, Kishimoto Yoshimi, Saita Emi, Ohmori Reiko, Nakamura Masato, Kondo Kazuo, Momiyama Yukihiko
Department of Cardiology, NHO Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan.
Department of Cardiovascular Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.
Heart Vessels. 2025 Mar;40(3):219-226. doi: 10.1007/s00380-024-02465-8. Epub 2024 Sep 28.
Excessive apoptosis and its insufficient clearance is characteristic of atherosclerotic plaques. Fortilin has potent antiapoptotic property and is abundantly expressed in atherosclerotic plaques. Fortilin-deficient mice had less atherosclerosis with more macrophage apoptosis. Recently, we reported that plasma fortilin levels were high in patients with coronary artery disease (CAD). However, its prognostic value has not been elucidated. We investigated plasma fortilin levels and major adverse cardiovascular events (MACE) in 404 patients (mean age 68 ± 12 years; 276 males) undergoing coronary angiography for suspected CAD. MACE was defined as cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or coronary revascularization. Of the 404 patients, 218 (54%) had CAD. Plasma fortilin levels were higher in patients with CAD than without CAD (median 74.9 vs. 70.9 pg/mL, p < 0.05). During a mean follow-up of 5.7 ± 4.2 years, MACE was observed in 59 (15%) patients. Notably, patients with MACE had higher fortilin levels (median 83.0 vs. 71.4 pg/mL) and more often had fortilin level > 80.0 pg/mL (54% vs. 36%) than those without MACE (p < 0.025). A Kaplan-Meier analysis showed lower event-free survival in patients with fortilin > 80.0 pg/mL than in those with ≤ 80.0 pg/mL (p < 0.001). In multivariate Cox proportional hazards analysis, fortilin level (> 80.0 pg/mL) was an independent predictor of MACE (hazard ratio: 2.29, 95%CI: 1.36-3.85, p < 0.002). Among the 218 patients with CAD, fortilin level was also a significant predictor of MACE (hazard ratio: 2.48; 95%CI: 1.34-4.61, p < 0.005). Thus, high plasma fortilin levels were found to be associated with cardiovascular events in patients with CAD as well as those undergoing coronary angiography.
过度凋亡及其清除不足是动脉粥样硬化斑块的特征。福替林具有强大的抗凋亡特性，且在动脉粥样硬化斑块中大量表达。福替林缺陷小鼠的动脉粥样硬化程度较轻，但巨噬细胞凋亡较多。最近，我们报道冠状动脉疾病（CAD）患者的血浆福替林水平较高。然而，其预后价值尚未阐明。我们对404例因疑似CAD接受冠状动脉造影的患者（平均年龄68±12岁；男性276例）的血浆福替林水平和主要不良心血管事件（MACE）进行了研究。MACE定义为心血管死亡、心肌梗死、不稳定型心绞痛、心力衰竭、中风或冠状动脉血运重建。在404例患者中，218例（54%）患有CAD。CAD患者的血浆福替林水平高于无CAD患者（中位数74.9 vs. 70.9 pg/mL，p<0.05）。在平均5.7±4.2年的随访期间，59例（15%）患者发生了MACE。值得注意的是，发生MACE的患者福替林水平较高（中位数83.0 vs. 71.4 pg/mL），且福替林水平>80.0 pg/mL的情况比未发生MACE的患者更常见（54% vs. 36%，p<0.025）。Kaplan-Meier分析显示，福替林>80.0 pg/mL的患者无事件生存率低于福替林≤80.0 pg/mL的患者（p<0.001）。在多变量Cox比例风险分析中，福替林水平（>80.0 pg/mL）是MACE的独立预测因素（风险比：2.29，95%CI：1.36-3.85，p<0.002）。在218例CAD患者中，福替林水平也是MACE的显著预测因素（风险比：2.48；95%CI：-4.61，p<0.005）。因此，发现高血浆福替林水平与CAD患者以及接受冠状动脉造影的患者的心血管事件相关。 1.34
