【作者】 李杰；

【导师】 苗志林；

【作者基本信息】 中国医科大学 ， 内科学（专业学位）， 2021， 硕士

【摘要】 目的:冠状动脉微血管疾病(coronary microvascular disease,CMVD)是指影响冠状动脉微血管结构和(或)功能的一组疾病,在具有多种心血管危险因素的患者中普遍存在,并会增加不良心血管事件的发生率。事实上,在接受有创冠状动脉造影的心绞痛患者中,高达40%的患者未发现明显的心外膜血管狭窄,其中约60%的患者有CMVD的证据。目前关于CMVD的发病机制尚不清楚,但有研究表明,心血管危险因素引起的慢性炎症反应、氧化应激等病理表现与微血管内皮功能障碍的损害有关。近年来,中性粒细胞/淋巴细胞比值(neutrophil lymphocyte ratio,NLR)作为炎症反应的标志物之一,在代谢综合征、心房颤动和冠状动脉粥样硬化等疾病中都有研究,且被证实,NLR在心血管事件的诊断和预后评估方面有独特的价值。此外,过去在对心脏X综合征(cardiac syndrome X,CSX)患者的研究中发现,NLR与C反应蛋白对CSX有较好的预测效能。目前,CMVD的诊断主要依靠间接的功能评估,而与冠脉血流储备(coronary flow reserve,CFR)指标相比,微循环阻力指数(Index of microcirculatory resistance,IMR)因其变异性低、可重复性强及不受血流动力学影响等特点,更被大家认可,也是诊断CMVD的金标准。但现今CMVD的诊断方法都因操作程序复杂、价格昂贵等限制,难以在临床上推广。因此,本研究通过测定IMR诊断CMVD,旨在探讨NLR及其它相关临床指标与CMVD的相关性,试图寻找简便、无创、可靠的临床指标来预测CMVD。方法:选取2018年11月至2020年11月就诊于辽宁省人民医院的心绞痛患者,行冠状动脉造影排除外膜冠脉限流性狭窄(FFR≥0.80)后测定IMR,同时收集患者临床和实验室资料。NLR由血常规计算得出。根据IMR测量结果,将患者分为CMVD组(IMR≥25)和对照组(IMR<25)。比较两组NLR及临床化验指标的差异,并进行相关性分析。对于病例组,进一步采用Logistic多因素回归分析法对CMVD患者的危险因素进行分析。绘制ROC曲线评估NLR对CMVD的预测效能。结果:1.共纳入患者74例,男性43例,女性31例。CMVD组31例,其中男性19例,女性12例,平均年龄59.52±8.49,平均IMR测量值29.70±2.70;对照组43例,其中24例,女性10例,平均年龄58.47±10.40,平均IMR测量值20.80±3.40。两组间在年龄、性别、高血压、体重指数比较,差异均无统计学意义(p>0.05);CMVD组糖尿病(60.90%vs 39.10%,p=0.025)和吸烟(54.10%vs 45.90%,p=0.029)比例明显高于对照组(p<0.05)。2.两组血常规及生化结果比较,CMVD组患者的NLR(2.76±0.93 vs 1.90±0.64,p=0.001)、LDL-C(2.90±1.06 vs 2.68±1.05,p=0.038)均高于对照组,差异具有统计学意义(p<0.05),但两组间的WBC、RBC、HB、RDW等血常规指标及TC、TG、HDL-C等生化指标差异均无统计学差异(p>0.05)。3.简单的线性回归分析提示,NLR与IMR值呈良好的线性正相关。4.多因素Logistic回归分析,糖尿病、NLR、LDL-C是CMVD的独立危险因素。5.NLR用于诊断CMVD的ROC曲线下面积为0.782(95%CI:0.67～0.89,P=0.000)。结论:1.糖尿病、NLR及LDL-C是CMVD的独立危险因素,可能都参与了CMVD的发生发展,导致IMR值升高。2.NLR与IMR值具有良好的线性正相关关系,经ROC曲线分析得出,NLR对CMVD具有良好的预测价值。更多还原

【Abstract】 Objective: Coronary microvascular disease(CMD)refers to the subset of disorders affecting the structure and/or function of the coronary microvascular,is prevalent in patients across a broad spectrum of cardiovascular risk factors,and is associated with an increased risk of adverse events.In fact,after recepting the check of coronary angiography,there are 40% of patients with angina pectoris who did not find significant stenosis of epicardial artery.And 60% of them have CMVD.At present,the pathogenesis of CMVD is unclear,but studies have shown that chronic inflammatory response,oxidative stress and other pathological manifestations caused by cardiovascular risk factors are related to the damage of microvascular endothelial dysfunction.In recent years,as one of the markers of inflammatory response,neutrophil lymphocyte ratio(NLR)has been studied in diseases such as metabolic syndrome,atrial fibrillation and coronary atherosclerosisnd.And it has been demonstrated to have unique value in the diagnosis and prognosis evaluation of cardiovascular events.In addition,past studies for cardiac syndrome X(CSX)have found that NLR and C reactive proteins(CRP)have good predictive value on CSX.Currently,the diagnosis of CMVD depends mainly on indirect functional evaluation.Since Index of microcirculatory resistance(IMR)has the characteristics of low variability,strong repeatability and no hemodynamic influence,IMR is more recognized than coronary flow reserve(CFR).And IMR is the gold standard for diagnosis of CMVD.However,due to the complex and expensive operating procedures of IMR,it is difficult to be widely popularized in clinical application.Therefore,this study aims to explore the correlation between CMVD and NLR or other related clinical indicators after the determination of the CMVD by IMR,so as to attempts to find simple,non-invasive and reliable clinical indicators to predict the CMVD.Methods:First,the angina pectoris patients in Liaoning Provincial people’s Hospital from November 2018 to November 2020 were selected.Then they were given coronary angiography to exclude flow limiting stenosis of epicardial artery(FFR≥0.8).Next,the measurement of IMR was carried and clinical and laboratory data were collected.NLR is calculated by blood routine.Finally,the patients were divided into CMVD group(IMR≥25)and control group(IMR<25).Compare the difference of NLR and clinical test indexes between the two groups and analyze the correlation.For CMVD group,the risk factors of patient were further analyzed by Logistic multivariate regression analysis.The ROC curve is drawn to evaluate NLR prediction effectiveness of the CMVD.Results:1.A total of 74 patients including 43 males and 31 females were collected.For31 cases in CMVD group,19 cases are males,12 cases are females,average age is59.52±8.49 and average measured value of IMR is 20.80±3.40.There was no significant difference in age,grnder,hypertension and BMI between the two groups(p>0.05).Diabetes(60.90% vs 39.10%,p=0.025)and smoking(54.10% vs.45.90%,p=0.029)were significantly higher of CMVD group than of control group.2.Comparison of blood routine and biochemical results between the two groups showed that NLR(2.76±0.93 vs1.90±0.64,p=0.001),LDL-C(2.90±1.06 vs 2.68±1.05,p=0.038)in the CMVD group were significantly higher than those in the control group(p<0.05).However,there was no significant difference in blood routine indexes such as WBC,RBC,HB,RDW and biochemical indexes such as TC,TG and HDL-C between the two groups.3.Simple linear regression analysis shows that there is a good linear positive correlation between NLR and IMR.4.The multivariate logistic regression analysis showed that diabetes,NLR and PLR were independent risk factors for CMVD.5.The area under the ROC curve of NLR used to diagnose patients with CMVD was 0.7820(95%CI:0.67～0.89,P=0.000)Conclusion:1.Diabetes,NLR and LDL-C are independent risk factors for CMVD,which may be involved in the occurrence and development of CMVD,resulting in the increase of IMR.2.There is a good linear positive correlation between NLR and IMR.Through the analysis of ROC curve,it is concluded that NLR has good predictive value for CMVD.更多还原