Servergazi State Hospital, Department of Emergency Medicine, Denizli, Turkey
Department of Biophysics, Pamukkale University Medical Faculty, Denizli, Turkey.
In Vivo. 2019 Sep-Oct;33(5):1581-1592. doi: 10.21873/invivo.11640.
BACKGROUND/AIM: Endoplasmic reticulum (ER) stress plays a critical role in the development of cardiac hypertrophy and heart failure. Heart failure is a crucial health problem that affects 23 million people worldwide, causes approximately 2.4 million people to be hospitalized every year in the USA, and leads to the death of more than 300,000 people. In this study, we aimed to investigate the clinical significance of ER stress markers and the predictive value of acute decompensated heart failure in patients with low ejection fraction heart failure (ADHF).
This is a prospective case control study. The data included laboratory parameters pertaining to patients with ADHF in the emergency service and lipid parameters obtained during their admission to the hospital. In addition, the same parameters obtained from the control group patients with chronic heart failure (CHF) during their routine polyclinic control were recorded in the data set. Admission time to the hospital and length of hospital stay were included in the data. The levels of glucose regulated protein (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) in peripheral blood serum obtained from the patients and the control group were measured using the ELISA method.
Serum GRP78 concentration was lower in the HF group (p=0.003) compared to the control. The median value of serum PERK concentration in the HF group was higher than that of the control group (573 pg/ml, IQR=477.5-650 vs. 495.5 pg/ml, IQR=294-648, respectively) (p=0.001). However, there were no statistically significant differences in GRP78 and PERK serum concentrations between ADHF and CHF subgroups. Receiver operating characteristic (ROC) curve analysis showed greater area under the curve (AUC) for the serum GRP78 levels of the healthy individuals (AUC=0.748, 95% CI=0.681-0.814, p=0.0003). The serum GRP78 level was found to be 80% sensitive and 70% specific at 147.5 pg/ml (p=0.0003) for distinguishing healthy individuals from HF patients. In the ADHF subgroup, there was a moderate correlation between hospitalization time and serum CHOP concentrations (Spearman rho=0.586 and p=0.001).
High GRP78 serum concentration may protect the patient from ER stress. In addition, the serum PERK level is high in patients with HF, whereas it is insufficient in predicting acute decompensation. CHOP may be useful in predicting the length of hospital stay in patients with ADHF.
背景/目的：内质网（ER）应激在心肌肥厚和心力衰竭的发展中起着关键作用。心力衰竭是一个严重的健康问题，影响着全球 2300 万人，导致美国每年约有 240 万人住院，超过 30 万人死亡。本研究旨在探讨 ER 应激标志物在射血分数降低的心力衰竭（ADHF）患者中的临床意义和急性失代偿性心力衰竭的预测价值。
这是一项前瞻性病例对照研究。数据包括急诊科 ADHF 患者的实验室参数和入院时的血脂参数。此外，还记录了在常规综合诊所控制下慢性心力衰竭（CHF）对照组患者的相同参数。入院时间和住院时间也包含在数据中。使用 ELISA 法测量患者和对照组外周血血清中葡萄糖调节蛋白（GRP78）、蛋白激酶 RNA 样内质网激酶（PERK）和 C/EBP 同源蛋白（CHOP）的水平。
HF 组血清 GRP78 浓度低于对照组（p=0.003）。HF 组血清 PERK 浓度中位数高于对照组（573pg/ml，IQR=477.5-650 与 495.5pg/ml，IQR=294-648，分别）（p=0.001）。然而，ADHF 和 CHF 亚组之间的 GRP78 和 PERK 血清浓度无统计学差异。受试者工作特征（ROC）曲线分析显示，健康个体的血清 GRP78 水平曲线下面积（AUC）更大（AUC=0.748，95%CI=0.681-0.814，p=0.0003）。在区分健康个体和 HF 患者时，血清 GRP78 水平为 147.5pg/ml 时具有 80%的敏感性和 70%的特异性（p=0.0003）。在 ADHF 亚组中，住院时间与血清 CHOP 浓度之间存在中度相关性（Spearman rho=0.586，p=0.001）。
高 GRP78 血清浓度可能使患者免受 ER 应激。此外，HF 患者的血清 PERK 水平较高，但不足以预测急性失代偿。CHOP 可能有助于预测 ADHF 患者的住院时间。
