【作者】 张岩；

【导师】 张妍；

【作者基本信息】 大连医科大学 ， 内科学， 2022， 硕士

【摘要】 背景和目的:低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)作为动脉粥样硬化性心血管疾病(Atherosclerotic cardiovascular disease,ASCVD)血脂管理的首要干预靶点,其目标值备受关注。近年来多项研究显示,进一步降低LDL-C水平可以更为显著的降低心血管病患者的不良事件风险。因此,行经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)的冠心病患者作为极高危人群,欧美国家指南推荐其LDL-C目标水平由以往的1.8mmol/L降至1.4mmol/L以下。在我国,随着胆固醇吸收抑制剂、PCSK9抑制剂等的临床应用,使LDL-C进一步降低成为可能,是否LDL-C靶目标越低越好,以及LDL-C进一步降低对极高危患者预后及安全性是否带来更多获益,我们还需掌握真实世界情况。本研究旨在探讨两种不同LDL-C靶目标水平对冠心病患者行PCI治疗预后及安全性的影响,从而指导临床治疗,改善疾病预后。方法:选取2019年1月至2020年1月于大连医科大学附属第一医院行PCI治疗且术后1月复查LDL-C<1.8mmol/L的患者。根据术后1月复查LDL-C水平,分为A组(1.4mmol/L≤LDL-C<1.8mmol/L)和B组(LDL-C<1.4mmol/L),收集患者的一般临床资料、既往史、相关化验及检查、用药情况等,对其随访12个月,记录主要不良心血管事件(major adverse cardiac event,MACE)的发生时间和详细情况、血脂水平以及药物不良反应,比较两组MACE事件的发生有无差异,分析发生MACE事件的影响因素以及对安全性进行评价。结果:1.本研究共纳入PCI术后1月复查LDL-C<1.8mmol/L的患者409例,其中A组(1.4mmol/L≤LDL-C<1.8mmol/L)235例,B组(LDL-C<1.4mmol/L)174例,男性319例(78%),女性90例(22%),平均患病年龄为65.59±10.88岁,高危因素有高血压(255例,62%)、吸烟(186例,45%)、糖尿病(158例,38.6%)。2.临床资料比较:A组男性构成比显著较低(P<0.001),D-二聚体、总胆固醇、高密度脂蛋白胆固醇、非高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、脂蛋白a水平均显著较高(p<0.05),余吸烟史、饮酒史、年龄、BMI、高血压病史、脑卒中病史、糖尿病病史、既往PCI、既往心肌梗死病史、房颤史、冠心病分型、相关化验及检查、口服用药类型、血管病变情况无统计学差异(P>0.05)。3.MACE事件发生情况:两组患者发生MACE事件共73例(17.8%),其中再发心绞痛或心衰入院59例(80.8%),非致命性心肌梗死7例(9.6%),冠状动脉血运重建22例(30.1%),心源性死亡2例(2.7%),脑卒中7例(9.6%)。较B组,A组再发心绞痛或心衰入院发生率显著较高[18(10.3%)VS 41(17.4%)](p<0.05),MACE事件总体发生率显著较高[22(12.6%)VS 51(21.7%)](p<0.05),而非致命性心肌梗死、冠状动脉血运重建、心源性死亡、脑卒中的发生率无统计学差异(p>0.05)。4.生存分析:较B组,A组无MACE生存率显著较低(p<0.05)。5.COX回归多因素生存分析:发现非HDL-C水平增高、LDL-C是否<1.4mmol/L、既往心肌梗死病史是极高危冠心病患者PCI术后发生MACE事件的独立危险因素(p<0.05)。6.安全性评价:不同LDL-C目标水平下两组患者他汀药物不良反应无统计学差异(p>0.05)。结论:1.极高危冠心病患者PCI术后LDL-C水平降至1.4mmol/L以下较1.8mmol/L MACE事件的发生率较低。2.非HDL-C水平增高、既往心肌梗死病史以及LDL-C是否降至1.4mmol/L以下是极高危冠心病患者PCI术后发生MACE事件的独立危险因素。更多还原

【Abstract】 Background and objective:Low-density lipoprotein cholesterol(LDL-C),as the primary intervention target of blood lipid management in atherosclerotic cardiovascular disease(ASCVD),has attracted much attention.In recent years,a number of studies have shown that further reduction of LDL-C levels can more significantly reduce the risk of adverse events in patients with cardiovascular disease.Therefore,as an very-high-risk group,patients with coronary heart disease undergoing percutaneous coronary intervention(PCI),are recommended to reduce their LDL-C target level from theprevious 1.8 mmol/L to less than 1.4 mmol/L according to the guidelines of European and American countries.In China,with the clinical application of cholesterol absorption inhibitors and PCSK9 inhibitors,it is possible to further reduce LDL-C.But we still need to grasp the real world situation to find out Whether the lower the LDL-C target is,the better it will be,and whether further lowering LDL-C will bring more benefits to the prognosis and safety of extremely high-risk patients.This study aims to investigate the effects of two different LDL-C target levels on the prognosis and safety of PCI in patients with coronary heart disease,so as to guide clinical treatment and improve disease prognosis.Methods:Patients who underwent PCI in the First Affiliated Hospital of Dalian Medical University from January 2019 to January 2020 and had LDL-C<1.8 mmol/L 1month after surgery were selected.According to the reexamination of LDL-C level at 1 month after operation,the patients were divided into group A(1.4mmol/L≤LDL-C<1.8mmol/L)and group B(LDL-C<1.4mmol/L).The general clinical data,past history,relevant laboratory tests and examinations,medication,etc.of the patients were collected and followed up for 12 months.The occurrence time and details of major adverse cardiovascular event(MACE),blood lipid level andadverse drug reactions were recorded.The differences in the occurrence of MACE events between the two groups were compared.The influencing factors of MACE events were analyzed and the safety was evaluated.Results:1.A total of 409 patients with LDL-C<1.8mmol/L one month after PCI were chosen in this study,including 235 patients in group A(1.4mmol/L≤LDL-C<1.8mmol/L),174 patients in group B(LDL-C<1.4mmol/L),319 males(78%)and 90females(22%),with an average age of 65.59±10.88 years.The high riskfactors were hypertension(255 cases,62%),Smoking(186 cases,45%),and diabetes(158 cases,38.6%).2.Comparison of Clinical Data: The constituent ratio of males in group A was significantly lower(P<0.001),D-dimer,total cholesterol,high-density lipoprotein cholesterol,non-high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,and lipoprotein(a)levels were significantly higher(P<0.05),and there was no statistically significant difference(P>0.05)in the remaining parts such as smoking history,drinking history,age,BMI,hypertension history,stroke history,diabetes history,previous PCI,previous myocardial infarction history,atrial fibrillation history,coronary heart disease classification,related laboratory tests and examinations,type of oral medication,and vascular lesions.3.Occurrence of MACE Events: A total of 73 patients(17.8%)in the two groups had MACE events,among which 59 patients(80.8%)were admitted for recurrent angina pectoris or heart failure,7 patients(9.6%)had non-fatal myocardial infarction,22 patients(30.1%)had coronary revascularization,2 patients(2.7%)had cardiac death,and 7 patients(9.6%)had stroke.Compared with group B,group A had significantly higher incidence of recurrent angina pectoris or heart failure admission [18(10.3%)VS41(17.4%)](p<0.05),and significantly higher overall incidence of MACE events [22(12.6%)VS 51(21.7%)](p<0.05),while there was no statistical difference in the incidence of non-fatal myocardial infarction,coronary revascularization,cardiac death,and stroke(p>0.05).4.Survival Analysis: Compared with group B,the survival rate of group A was significantly lower(P<0.05).5.COX Regression Multivariate Survival Analysis: It was found that non-HDL-C level,LDL-C<1.4mmol/L,and previous history of myocardial infarction were independent risk factors for MACE events of post-PCI patients with very-high-risk coronary heart disease(P<0.05).6.Safety evaluation: There was no statistical difference in the adverse reactions of statins between the two groups under different LDL-C target levels(P>0.05).Conclusion:1.The incidence of MACE events in patients with very-high-risk coronary heart disease whose LDL-C levels below 1.4mmol/L after PCI was lower than that of1.8mmol/L.2.Non-HDL-C level,previous history of myocardial infarction and whether LDL-C decreased below 1.4mmol/L are independent risk factors for MACE events after PCI in patients with very-high-risk coronary heart disease.更多还原