Chen Xiangmei, Huang Xiao, Tian Huanhuan, Kong Guiqing, Hu Haoran, Lyu Bingjie, Liu Xiaoli, Lu Feng, Shang Quanmei, Hao Dong, Wang Xiaozhi, Wang Tao
Department of Critical Care Medicine, Binzhou Medical University Hospital, Binzhou 256603, Shandong, China. Corresponding author: Wang Tao, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2022 Jun;34(6):614-619. doi: 10.3760/cma.j.cn121430-20211220-01887.
To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis.
Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn.
There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [μg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [μg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95%CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (β value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 μg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly.
PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 μg/L, the 28-day survival rate decreased significantly.
探讨前蛋白转化酶枯草溶菌素9型（PCSK9）及血脂指标对脓毒症患者的预后价值。
选取2021年1月至10月滨州医学院附属医院重症医学科收治的年龄≥18岁且符合Sepsis-3.0诊断标准的脓毒症或脓毒性休克患者。选取同期健康成年人作为健康对照组。记录基线特征、急性生理与慢性健康状况评分系统II（APACHE II）及序贯器官衰竭评估（SOFA）评分。诊断后24小时内采集静脉血样，于诊断后1天、3天和5天采用酶联免疫吸附测定（ELISA）法测定血清PCSK9。同时检测高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、甘油三酯（TG）及脂蛋白A。比较脓毒症组（28天死亡组和存活组）与健康对照组各指标差异。同时比较脓毒症组不同严重程度及28天预后患者的指标。绘制受试者工作特征曲线（ROC曲线）评估PCSK9及血脂对脓毒症预后的预测价值。采用多因素Logistic回归分析脓毒症预后的影响因素，并绘制第28天的Kaplan-Meier生存曲线。
脓毒症组50例（包括脓毒症19例，脓毒性休克31例），健康对照组27例。脓毒症组中，28天内19例死亡，31例存活。脓毒症组血清PCSK9显著高于健康对照组[μg/L：223.09（198.47，250.82）vs. 188.00（165.27，214.90），P<0.01]，HDL-C、LDL-C、TC及脂蛋白A显著低于健康对照组[HDL-C（mmol/L）：0.82±0.35 vs. 1.45±0.24，LDL-C（mmol/L）：1.53（1.14，2.47）vs. 2.89（2.55，3.19），TC（mmol/L）：2.03（1.39，2.84）vs. 4.24（3.90，4.71），脂蛋白A（g/L）："8.80（5.66，17.56）vs. 27.03（14.79，27.03），均P<0.01]"。脓毒症死亡组PCSK9高于存活组[μg/L：249.58（214.90，315.77）vs. 207.01（181.50，244.95），P<0.01]，HDL-C、LDL-C及TC低于存活组[HDL-C（mmol/L）：0.64±0.35 vs. 0.93±0.30，LDL-C（mmol/L）：1.32±0.64 vs. 2.08±0.94，TC（mmol/L）：1.39（1.01，2.2"3）vs. 2.69（1.72，3.81），均P<0.01]"。随着病情进展，脓毒症死亡组和存活组PCSK9均显著低于诊断后1天（均P<0.05）。ROC曲线分析显示，PCSK9对28天死亡的预测价值高于HDL-C、LDL-C、TC[ROC曲线下面积（AUC）及95%置信区间（95%CI）：0.748（0.611-0.885）vs. 0.710（0.552-0.868），0.721（0.575-0.867），0.702（0.550-0.854）]。多因素Logistic回归分析显示，PCSK9是影响脓毒症28天预后的独立危险因素（β值为1.014，P=0.020）。Kaplan-Meier生存曲线分析显示，当PCSK9≥208.97μg/L时，随着PCSK9升高，脓毒症患者28天生存率显著降低。
PCSK9、HDL-C、LDL-C及TC均可预测脓毒症患者28天预后。PCSK9的预后价值最高。PCSK9是影响脓毒症预后的独立危险因素。在疾病早期，PCSK9可能对脓毒症预后具有良好的预测价值。当PCSK9≥208.97μg/L时，28天生存率显著降低。
