缺血性卒中二级预防后复发的危险因素及药物干预对4-HNE浓度的影响

Effects of Risk Factors for the Recurrence of Ischemic Stroke after Secondary Prevention and the Effect of Drug Intervention on the Concentration of 4-HNE

目的:探讨缺血性卒中二级预防后复发的危险因素,并观察谷胱甘肽对4-HNE浓度的影响。方法:以2017年10月-2019年10月于山东第一医科大学第二附属医院等3家医院因脑血栓或脑栓塞住院治疗的97例缺血性卒中1年内复发患者为观察组,以同期97例未复发患者为对照组并进行配对。观察组患者按分层随机抽样法又分为常规治疗组(49例)和药物干预组(48例)。常规治疗组患者于住院期间进行脑血流再通、改善循环、控制血压、维持血糖、治疗高脂血症和心律失常等常规治疗,药物干预组患者在常规治疗组治疗的基础上加用注射用谷胱甘肽1.8 g,每天1次,静脉注射;疗程均为14天。均于入院时及治疗14天后测定血浆中4-HNE浓度,均于入院时检测ALDH2基因分型和TOAST分型。采用多元线性回归分析探讨4-HNE升高的相关因素;采用条件Logistic分析探讨缺血性卒中二级预防后复发的独立危险因素。结果:观察组患者入院时血浆中4-HNE浓度、大动脉粥样硬化患者比例均显著高于对照组(P<0.05)。两组患者的ALDH2各基因型分布均符合Hardy-Weinberg遗传平衡定律(P>0.05)。观察组携带ALDH2*2等位基因的患者比例(50.50%)显著高于对照组(36.08%)(P<0.05)。携带ALDH2*2等位基因[B=2.33,95%CI(1.35,5.50),P=0.03]和大动脉粥样硬化[B=1.90,95%CI(1.29,3.74),P=0.04]与4-HNE浓度升高显著相关;大动脉粥样硬化[OR=2.93,95%CI(1.84,4.67),P<0.01]、卒中家族史[OR=1.50,95%CI(1.18,1.90),P=0.04]、血浆中4-HNE浓度升高[OR=1.34,95%CI(1.11,1.62),P=0.04]是缺血性卒中二级预防后复发的独立危险因素。干预后,药物干预组和常规治疗组患者血浆中4-HNE浓度均显著低于同组干预前(P<0.05);而两组组间比较,差异均无统计学意义(P>0.05)。结论:卒中家族史、大动脉粥样硬化、血浆中4-HNE浓度升高是缺血性卒中二级预防后复发的独立危险因素;尽管药物干预能降低患者血浆中4-HNE浓度,但加用谷胱甘肽的效果并不比常规治疗显著。

OBJECTIVE:To investigate the risk factors for the recurrence of ischemic stroke after secondary prevention,and to observe the effect of glutathione on 4-HNE.METHODS:Totally 97 patients with ischemic stroke relapse within one year were treated from Oct.2017 to Oct.2019 in 3 hospitals as the Second Affiliated Hospital of Shandong First Medical University due to cerebral thrombosis or cerebral embolism as observation group,and 97 non-recurrence patients in the same period were paired as control group.The patients in the observation group were randomly divided into conventional treatment group(49 cases)and drug intervention group(48 cases).The patients in conventional treatment group received routine treatment such as cerebral blood flow recanalization,improving circulation,controlling blood pressure,maintaining blood glucose,treating hyperlipidemia and arrhythmia during hospitalization.Drug intervention group was additionally given Glutathione for injection 1.8 g intragastrically,once a day,on the basis of conventional treatment group.4-HNE concentrations in plasma were determined at admission and 14 days after treatment,the genetic type of ALDH2 and type of TAST were determined at admission.Multiple liner regression was used to analyze the factors associated with 4-HNE increasing;conditional Logistic analysis was used to identify independent risk factors resulting to ischemic stroke recurrence after secondary prevention.RESULTS:The plasma concentration of 4-HNE at admission and the percentage of artery atherosclerosis patients in observation group were significantly higher than control group(P<0.05).The distribution of each ALDH2 genotype in 2 groups complied with Hardy-Weinberg genetic equilibrium(P>0.05).The proportion of patients carrying ALDH2*2 allele in observation group(50.50%)was significantly higher than control group(36.08%)(P<0.05).ALDH2*2 allele[B=2.33,95%CI(1.35,5.50),P=0.03]and artery atherosclerosis[B=1.90,95%CI(1.29,3.74),P=0.04]were significantly associated with the elevation of plasma concentration of 4-HNE;artery atherosclerosis[OR=2.93,95%CI(1.84,4.67),P<0.01],stroke family history[OR=1.50,95%CI(1.18,1.90),P=0.04],elevated plasma concentration of 4-HNE[OR=1.34,95%CI(1.11,1.62),P=0.04]were regarded as independent risk factors associating with ischemic stroke recurrence after secondary prevention.After intervention,plasma concentration of 4-HNE in drug intervention group and conventional treatment group was significantly lower than before intervention(P<0.05);there was no statistical significance between 2 groups(P>0.05).CONCLUSIONS:Stroke family history,artery atherosclerosis and the elevation plasma concentration of 4-HNE are independent risk factors associating with ischemic stroke recurrence after secondary prevention.Although drug intervention can reduce the elevated plasma concentration of 4-HNE,the effect of additional use of glutathione is not more significant than that of conventional treatment.