PCSK9抑制剂对穿支动脉粥样硬化病患者早期神经功能恶化的影响  

Effect of PCSK9 inhibitors on early neurological deterioration in patients with branch atheromatous disease

作　　者：朱利利 付胜奇 秦海强[2] 禹萌 李浩然 刘海涛[1] 宋良[1] Zhu Lili;Fu Shengqi;Qin Haiqiang;Yu Meng;Li Haoran;Liu Haitao;Song Liang(Department of Neurology,the Fifth Clinical Medical College of Henan University of Chinese Medicine(Zhengzhou Peoples Hospital),Zhengzhou 450003,China;Neurology Center,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China)

机构地区：[1]河南中医药大学第五临床医学院(郑州人民医院)神经内科,郑州450003 [2]首都医科大学附属北京天坛医院神经病学中心,北京100070

出　　处：《中华医学杂志》2023年第37期2940-2946,共7页National Medical Journal of China

基　　金：国家自然科学基金(82271299);北京市科技计划(Z221100007422051);河南省医学科技攻关计划省部共建项目(SB201903029)

摘　　要：目的探讨前蛋白转化酶枯草杆菌蛋白酶/kexin9型(PCSK9)抑制剂在穿支动脉粥样硬化病(BAD)治疗过程中对早期神经功能恶化发生率的影响。方法回顾性纳入郑州人民医院2020年1月至2023年4月于神经内科住院的BAD患者297例,根据是否使用PCSK9抑制剂治疗分为PCSK9抑制剂组81例和对照组216例,运用倾向性评分匹配(PSM)方法,消除PCSK9抑制剂组和对照组患者的一般情况差异,两组各成功匹配72例,主要比较患者早期神经功能恶化(END)及低密度脂蛋白胆固醇(LDL-C)等相关指标;采用卒中后72 h内美国国立卫生研究院卒中量表(NIHSS)评分增加≥2分定义END,筛选出导致END的可疑影响因素进行多因素logistic回归模型分析。结果PSM匹配后144例患者中男90例,女54例,年龄(61.2±9.6)岁。匹配后PCSK9抑制剂组患者住院时间[M(Q_(1),Q_(3))][9(7,11)d比10(8,13)d]、出院时NIHSS评分[2(1,3)分比3(1,4)分]与对照组相比,差异有统计学意义(均P<0.05);此外,PCSK9抑制剂组END发生率降低[12.5%(9/72)比31.9%(23/72),P<0.05],多因素logistic回归模型分析发现C反应蛋白(CRP)(OR=1.119,95%CI:1.010~1.240,P<0.05)和使用PCSK9抑制剂(OR=0.298,95%CI:0.117~0.755,P<0.05)是END发生的相关因素。结论BAD患者治疗中应用PCSK9抑制剂可以降低END的发生率。Objective To investigate the effect of Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9)inhibitors on the incidence of early neurological deterioration during the treatment of branch atheromatous disease(BAD).Methods A retrospective analysis of 297 BAD patients admitted to the Department of Neurology in Zhengzhou People′s Hospital from January 2020 to April 2023 was made.According to whether to use PCSK9 inhibitor treatment,they were divided into PCSK9 inhibitor group(81 cases)and control group(216 cases).Propensity score matching(PSM)method was used to eliminate the general situation difference between PCSK9 inhibitor group and control group.Seventy-two cases were successfully matched in each group.The early neurological deterioration(END)and low-density lipoprotein cholesterol(LDL-C)were compared.END was defined as the National Institutes of Health Stroke Scale(NIHSS)score increase≥2 points within 72 hours after stroke.Suspicious influencing factors leading to END were screened for multivariate logistic regression model analysis.Results After PSM matching,among the 144 patients,90 were male and 54 were female,aged(61.2±9.6)years.After matching,The hospital stay[M(Q_(1),Q_(3))][9(7,11)d vs 10(8,13)d]in PCSK9 and NIHSS score at discharge[2(1,3)vs 3(1,4)points]were significantly different from those in the control group(all P<0.05).In addition,the incidence of END was reduced in the PCSK9 inhibitor group[12.5%(9/72)vs 31.9%(23/72),P<0.05].Multivariate logistic regression analysis found that C-reactive protein(CRP)(OR=1.119,95%CI:1.010-1.240,P<0.05)and PCSK9 inhibitor(OR=0.298,95%CI:0.117-0.755,P<0.05)were factors associated with the development of END.Conclusion The use of PCSK9 inhibitors in the treatment of patients with BAD can reduce the incidence of END.

关 键 词：动脉粥样硬化 PCSK9抑制剂 早期神经功能恶化 穿支动脉粥样硬化病 倾向性评分匹配 回顾性队列研究 

分 类 号：R543.5[医药卫生—心血管疾病]