PCSK9及血脂对脓毒症患者预后的预测价值

Prognostic value of PCSK9 and blood lipid in patients with sepsis

目的探讨前蛋白转化酶枯草溶菌素9(PCSK9)及血脂指标对脓毒症患者预后的预测价值。方法选择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岁且符合脓毒症3.0诊断标准的脓毒症及脓毒性休克患者作为研究对象;以同期健康体检者作为健康对照组。记录患者的基本信息及急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)和序贯器官衰竭评分(SOFA);于确诊1、3、5 d取静脉血,采用酶联免疫吸附试验(ELISA)测定血清PCSK9水平,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)、三酰甘油(TG)、脂蛋白a水平。比较脓毒症组与健康对照组各指标的差异;同时比较脓毒症组中不同病情严重程度及不同28 d预后患者各指标的差异。绘制受试者工作特征曲线(ROC曲线),评估PCSK9、血脂指标对脓毒症患者28 d预后的预测价值,用多因素Logistic回归分析影响预后的因素,并绘制28 d Kaplan-Meier生存曲线。结果脓毒症组共50例(其中脓毒症19例、脓毒性休克31例),健康对照组27例;脓毒症组中28 d死亡19例,存活31例。脓毒症组血清PCSK9较健康对照组明显升高〔μg/L:223.09(198.47,250.82)比188.00(165.27,214.90),P<0.01〕,HDL-C、LDL-C、TC、脂蛋白a较健康对照组明显降低〔HDL-C(mmol/L):0.82±0.35比1.45±0.24,LDL-C(mmol/L):1.53(1.14,2.47)比2.89(2.55,3.19),TC(mmol/L):2.03(1.39,2.84)比4.24(3.90,4.71),脂蛋白a(g/L):8.80(5.66,17.56)比27.03(14.79,27.03),均P<0.01〕;脓毒症死亡组PCSK9较存活组明显升高〔μg/L:249.58(214.90,315.77)比207.01(181.50,244.95),P<0.01〕,HDL-C、LDL-C、TC较存活组明显降低〔HDL-C(mmol/L):0.64±0.35比0.93±0.30,LDL-C(mmol/L):1.32±0.64比2.08±0.94,TC(mmol/L):1.39(1.01,2.23)比2.69(1.72,3.81),均P<0.01〕。随疾病进展,脓毒症死亡组与存活组PCSK9均较确诊1 d时明显下降(均P<0.05)。ROC曲线分析显示,PCSK9对患者28 d死亡的预测价值高于HDL-C、LDL-C和TC〔ROC曲线下面积(AUC)和95%可信区间(95%CI):0.748(0.611~0.885)比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是影响脓毒症患者28 d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 d生存率明显下降。结论PCSK9、HDL-C、LDL-C、TC均可预测脓毒症患者28 d预后,PCSK9预测预后价值高于HDL-C、LDL-C和TC;PCSK9是影响脓毒症患者预后独立危险因素,在疾病早期,PCSK9可能对脓毒症预后有较好预测价值,当PCSK9≥208.97μg/L时,28 d生存率明显下降。

Objective To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9(PCSK9)and blood lipid indexes in patients with sepsis.Methods 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 evaluationⅡ(APACHEⅡ)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.Results 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(βvalue was 1.014,P=0.020).Kaplan-Meier survival curve analysis showed that when PCSK9≥208.97μg/L,with the increase of PCSK9,the 28-day survival rate of sepsis patients decreased significantly.Conclusions 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≥208.97μg/L,the 28-day survival rate decreased significantly.