残余胆固醇与进展为主要不良心血管事件的非罪犯病变易损斑块的相关性研究

Association of Residual Cholesterol with Vulnerable Plaques in Non-culprit Lesions Progressing to Major Adverse Cardiovascular Events

背景 残余胆固醇(RC)被认为是动脉粥样硬化性心血管疾病的重要危险因素,而冠状动脉非罪犯病变(NCCLs)进展也是影响冠心病患者预后的重要因素,但是残余胆固醇与进展为主要不良心血管事件(MACE)的NCCLs易损斑块的关系尚不明确。目的 探讨RC对发生MACE的NCCLs易损斑块的预测价值及长期预后的相关性。方法 选取2015年2月—2022年2月于新疆医科大学第一附属医院心脏中心住院的488例冠心病患者为研究对象,通过电子病历系统收集患者基线资料,行冠状动脉造影及光学相干断层扫描OCT。入组患者在出院1、3、6和12个月接受预定随访。采用Spearman秩相关检验探究RC与NCCLs中薄纤维帽粥样硬化斑块(TCFA)斑块特征的相关性。采用多因素Logistic回归分析探究NCCLs中TCFA发生MACE的影响因素。绘制受试者工作特征曲线(ROC曲线)并计算ROC曲线下面积(AUC),探究RC对NCCLs中TCFA发生MACE的预测价值。结果 共纳入488例冠心病患者,根据NCCLs是否发生MACE将患者分为发生MACE组(n=38)和未发生MACE组(n=450)。通过OCT识别NCCLs的斑块特征,共分析了749个NCCLs斑块,304个NCCLs斑块最小管腔面积(MLA)<3.5 mm^(2)。随访期间38例(7.8%)患者共发生了41例次NCCLs斑块引起的MACE事件,18例(3.7%)患者发生了支架内再狭窄,15例(3.1%)发生了不确定因素的死亡。发生MACE组患者高血压、糖尿病、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、RC、糖化血红蛋白(Hb A1c)、TCFA、MLA<3.5 mm^(2)比例高于未发生MACE组(P<0.05)。105例患者检查出TCFA,其中22例发生MACE(发生MACE的TCFA组),83例未发生MACE(未发生MACE的TCFA组)。发生MACE的TCFA组糖尿病比例与RC高于未发生MACE的TCFA组(P<0.05)。Spearman秩相关分析结果示,RC与最薄纤维帽厚度、MLA呈负相关(r_(s)=-0.665、-0.771,P<0.05),与最大脂质弧度、巨噬细胞浸润呈正相关(r_(s)=0.806、0.481,P<0.05)。多因素Logistic回归分析结果显示糖尿病(OR=3.410,95%CI=1.165~9.988,P=0.025)、高RC水平(OR=5.879,95%CI=1.436~24.073,P=0.014)是NCCLs中TCFA发生MACE的危险因素。绘制RC预测NCCLs中TCFA发生MACE的ROC曲线,结果显示AUC为0.695(95%CI=0.571~0.819,P=0.005),最佳截断值为0.606 mmol/L,灵敏度、特异度分别为0.818、0.518。结论 RC水平升高可能是冠心病患者中NCCLs易损斑块发生MACE的危险因素,对NCCLs中TCFA发生MACE有一定的预测价值。

Background Remnant cholesterol(RC)is considered a significant risk factor for atherosclerotic cardiovascular diseases,and the progression of non-culprit coronary lesions(NCCLs)is also a prominent issue affecting the prognosis of patients with coronary artery disease.However,the relationship between residual cholesterol and vulnerable plaques in NCCLs that progress to major adverse cardiovascular events(MACE)is not well understood.Objective To explore the predictive value of RC for vulnerable plaques in NCCLs that develop MACE and its correlation with long-term prognosis.Methods A total of 488 patients with coronary artery disease admitted to the Cardiac Center of the First Affiliated Hospital of Xinjiang Medical University from February 2015 to February 2022 were selected as the study subjects.Baseline data of the patients were collected through the electronic medical record system,and coronary angiography and optical coherence tomography(OCT)were performed.Enrolled patients received scheduled follow-up at 1,3,6,and 12 months after discharge.Spearman's rank correlation test was used to explore the correlation between RC and the characteristics of thin-cap fibroatheroma(TCFA)plaques in NCCLs.Multiple Logistic regression analysis was used to explore the influencing factors of MACE in TCFA of NCCLs.The receiver operating characteristic curve(ROC curve)was plotted,and the area under the ROC curve(AUC)was calculated to explore the predictive value of RC for MACE in TCFA of NCCLs.Results A total of 488 coronary artery disease patients were included,and patients were divided into MACE group(n=38)and non-MACE group(n=450)based on whether NCCLs developed MACE.Plaque characteristics of NCCLs were identified by OCT,and a total of 749 NCCL plaques were analyzed,with 304 NCCL plaques having a minimum lumen area(MLA)<3.5 mm^(2).During the follow-up period,38 patients(7.8%)experienced 41 MACE events caused by NCCL plaques,18 patients(3.7%)developed in-stent restenosis,and 15 patients(3.1%)had deaths due to uncertain factors.The proportion of patients with hypertension,diabetes,total cholesterol(TC),2 low-density lipoprotein cholesterol(LDL-C),RC,glycated hemoglobin(HbA1c),TCFA,and MLA<3.5 mm in the MACE group was higher than that in the non-MACE group(P<0.05).TCFA was detected in 105 patients,of which 22 cases developed MACE(TCFA MACE group),and 83 cases did not develop MACE(non-TCFA MACE group).The proportion of diabetes and RC in the TCFA MACE group was higher than that in the non-TCFA MACE group(P<0.05).The results of Spearman's rank correlation analysis showed that RC was negatively correlated with the thinnest fibrous cap thickness and MLA(r_(s)=-0.665、-0.771,P<0.05),and positively correlated with the maximum lipid arc and macrophage infiltration(r_(s)=0.806、0.481,P<0.05).The results of Multiple Logistic regression analysis showed that diabetes(OR=3.410,95%CI=1.165~9.988,P=0.025)and high level of RC(OR=5.879,95%CI=1.436-24.073,P=0.014)was a risk factor for MACE in TCFA of NCCLs.The ROC curve for predicting MACE in TCFA of NCCLs by RC showed an AUC of 0.695(95%CI=0.571-0.819,P=0.005),with the optimal cutoff value of 0.606 mmol/L,and sensitivity and specificity of 0.818 and 0.518,respectively.Conclusion Elevated levels of RC may be a risk factor for the development of MACE in vulnerable plaques of NCCLs in patients with coronary artery disease,and it has certain predictive value for MACE in TCFA of NCCLs.