【作者】 李玲；

【导师】 王晨霞；

【作者基本信息】 延安大学 ， 内科学（专业学位）， 2021， 硕士

【摘要】 目的:血清纤维蛋白原/白蛋白比值(FAR)是一种与动脉粥样硬化相关的易于测量的新型炎症指标。本研究旨在探讨在冠心病(CHD)患者中FAR与冠脉病变程度的关系,分析FAR在不同临床类型冠心病中的差异,及其与己建立起来的全身炎症标志物的关联性,探索FAR用于预测冠脉病变严重程度的临床应用价值。方法:本研究回顾性选取了391例于2020年1月-2021年1月因胸闷等心前区不适症状在延安大学附属医院心脑血管分院心内科就诊并首次行冠脉造影(CAG)检查确诊的CHD患者,同期随机纳入242例冠脉CTA检查结果为阴性的患者组成非冠心病(Non-CHD)组。收集并如实记录以上纳入患者住院期间的基线特征,实验室化验指标、血管造影数据。记录所有患者高敏C反应蛋白(hs-CRP)及血常规中检验到的血清中性粒细胞计数(NEUT)、血小板计数(PLT)、淋巴细胞计数(LY),计算中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)。根据凝血七项检查检验到的血清纤维蛋白原(FIB)、白蛋白(ALB)水平,计算血清纤维蛋白原/白蛋白比值(FAR),参照冠心病相应临床类型诊断标准,将CHD患者划分为:稳定型心绞痛组(SAP组)共95例,年龄43-86岁;非ST段抬高型急性冠脉综合征组(NSTE-ACS组)199例,年龄47-87岁;ST段抬高型急性冠脉综合征组(STE-ACS组)97例,年龄40-83岁。CHD患者按照冠脉三大主支血管的病变数目,分为单一冠脉病变组188例,双重冠脉病变组121例,三重冠脉病变组82例。其中,多重冠脉病变被定义为包括双重冠脉病变和三重冠脉病变在内的2种血管病变。将CHD患者以Gensini评分(GS)等于20为临界点,分为低GS组(GS<20分)108例,和高GS组(GS≥20分)283例。根据预测高GS价值最大时的FAR临界值6.16,将CHD患者划分为低FAR组(FAR<6.16)136例,高FAR组(FAR≥6.16))255例。比较分析:1.临床类型分组(SAP组、NSTE-ACS组、STE-ACS组与Non-CHD组)四组间:⑴一般临床资料的差异;⑵炎症指标(FIB、ALB、FAR、hs-CRP、NLR、PLR)的差异;⑶CHD三种不同临床类型分组间GS的差异性。2.Spearman相关分析评价:CHD患者中FAR与已经建立起来的炎症指标(hs-CRP、NLR、PLR)的相关性。3.FAR与冠脉病变程度:⑴不同冠脉血管病变数目分组间,FAR及不同炎性指标(FIB、ALB、hs-CRP、NLR、PLR)、GS的差异性分析。⑵高、低GS两组间:(1)一般临床资料的差异性比较;(2)FAR及不同炎性指标(FIB、ALB、hs-CRP、NLR、PLR)的差异性比较。4.采用Spearman相关性分析讨论GS与FAR及不同炎性指标(hs-CRP、NLR、PLR)的相关性。5.FAR对冠脉病变程度的预测价值及临床应用价值:⑴构建二元Logistic回归模型筛选FAR、hs-CRP、NLR、PLR等相关指标是否为高GS的独立预测因子;⑵应用ROC曲线分析FAR、hs-CRP及两者同时应用(FAR+hs-CRP)对高GS预测能力;⑶FAR临床应用价值:比较高FAR、低FAR两组间三重冠脉血管病变发生率、STE-ACS发生率及GS的差异。结果:1.SAP组、NSTE-ACS组、STE-ACS组与Non-CHD组四间年龄、BMI在单因素方差分析中均未见统计学差异,各组间男性、高血压患者、糖尿病患者、吸烟者的比例,使用χ~2检验均未见显著差异;将TC、ALT、CRE指标进行Kruskal-Wallis H检验,未见明显差异(P均>0.05);CHD三组TG水平均显著高于Non-CHD组(P均<0.05),不同临床类型CHD组间两两比较时,均无显著差异(P均>0.05);LDL-C水平在四组间随冠脉病变临床类型的加重而逐渐升高,组间两两比较除在ACS组间(NSTE-ACS组、STE-ACS组)比较,LDL-C水平未见显著性差异外(P>0.05),其余组间两两比较均有显著差异(P均<0.05);HDL-C在CHD组明显低于Non-CHD组,CHD组组间比较发现SAP组明显高于STE-ACS组(P<0.05),而NSTE-ACS组分别与SAP组及STE-ACS组进行比较,均未见显著差异(P均>0.05)。2.FIB、NLR、hs-CRP在各组中比较趋势为:Non-CHD<SAP组<NSTE-ACS组<STE-ACS组;而ALB在Non-CHD组>SAP组>NSTE-ACS组>STE-ACS组,FAR:Non-CHD组<SAP组<NSTE-ACS组<STE-ACS组,在四组间两两比较时发现:SAP组FIB、FAR、NLR虽均高于Non-CHD组、ALB水平降低,但两组间进行比较均未见统计学差异(P均>0.05),而在不同类型CHD三组组间两两比较均有显著差异(P均<0.05)。PLR在STE-ACS组显著升高,明显高于其余三组,均具有统计学意义(P均<0.05),而三组间组内两两比较均未见统计学差异(P均>0.05),hs-CRP在四组间两两比较均有显著差异,(P均>0.05),可见FAR在一定程度上可以反映冠心病炎症负荷状态及冠脉病变的稳定性。3.GS在CHD三组间的比较为:SAP组<NSTE-ACS组<STE-ACS组,但NSTE-ACS组与STE-ACS组比较,无统计学意义(P<0.05),两组GS均明显高于SAP组(P均<0.05)。4.FAR与已经建立起来的全身炎症指标的关联性分析采用Spearman相关:FAR与hs-CRP、NLR、PLR均呈正相关(rs分别为0.822,0.463,0.296,P均<0.001),FAR与hs-CRP显著相关。5.在三组不同冠脉血管病变数目分组间FIB、FAR、hs-CRP、NLR、PLR均随着冠脉血管病变数目的增加而呈升高趋势,ALB水平则呈下降趋势。其中,多重冠脉病变组(双重冠脉病变组+三重冠脉病变组)与单一冠脉病变组比较,FIB、FAR及hs-CRP在多重冠脉病变组显著升高(P<0.05),而ALB在多重冠脉病变组显著降低(P<0.05),FIB、FAR、ALB、hs-CRP在多重冠脉病变组之间均未见显著差异。NLR、PLR在三重冠脉病变组均明显高于单一冠脉病变组和双重冠脉病变组(P均<0.05),而在双重冠脉病变组和单一冠脉病变组间未见统计学差异(P均>0.05)。GS随冠脉血管病变数目的增加也呈升高趋势,三组间两两比较均有明显差异(P均<0.05)。可见,FAR、hs-CRP在评估冠脉病变血管数目方面优于NLR、PLR。6.采用独立样本T检验分析高、低GS组间的年龄、BMI差异性,结果均未见显著差异(P均>0.05);两组间男性、高血压患者、糖尿病患者、吸烟者的比例,应用χ~2检验仍无显著差异(P均>0.05);对两组间TC、TG、ALT、CRE进行Mann-Whitney U检验,均无显著差异(P均>0.05)。LDL-C在高GS组显著升高,而HDL-C在高GS组显著降低(P均<0.05)。7.高GS组FIB、FAR、hs-CRP、NLR、PLR明显升高(P均<0.05),而ALB水平明显降低(P<0.001)。8.各项炎性指标与GS相关性研究发现,FAR(rs=0.407)?FIB(rs=0.325)?hs-CRP(rs=0.394)?NLR(rs=0.303)?PLR(rs=0.170)均与GS呈正相关关系;而ALB与GS呈负相关(rs=-0.333),显然FAR与GS的相关性最强?9.二元Logistic回归分析显示FAR(OR=1.274,95%CI:1.035-1.567,P<0.05)、hs-CRP(OR=1.757,95%CI:1.069-2.887,P<0.05)是高GS的独立预测因子,可以用于预测冠脉病变程度。10.高GS的FAR截断点为6.16[SN 76.7%,SP 64.8%,曲线下面积(AUC)为0.751,95%CI:0.698-0.804,P<0.001],hs-CRP的截断点为2.41(SN 74.9%,SP 64.8%,AUC为0.729,95%CI:0.671-0.788,P<0.001)。应用FAR+hs-CRP预测高GS的截断点为8.66(SN 72.8%,SP 68.5%,AUC为0.761,95%CI:0.708-0.815,P<0.001)。可见,FAR预测高GS的AUC高于hs-CRP,而同时应用两项指标预测高GS的AUC最大。11.高FAR组三重冠脉血管病变发生率、STE-ACS发生率及GS均明显高于低FAR组,均具有显著差异(P均<0.05)。提示着冠心病患者FAR水平超过6.16时,三重冠脉血管病变和STE-ACS发生的可能性更大、冠脉病变更严重,FAR具有一定的临床应用价值。结论:1.新型炎症指标FAR随冠心病临床类型的加重而呈升高趋势,有助于评估冠心病患者炎症负荷状态及冠脉病变的稳定性。2.FAR与已建立起来炎性指标呈正相关,与冠脉GS呈线性正相关,与冠心病患者冠脉病变程度关系密切。3.FAR为高GS的独立预测指标,同时应用FAR、hs-CRP可以提高对高GS的预测价值。4.FAR有助于评估冠心病患者冠脉血管病变数目及冠脉病变严重程度,具有临床应用价值。更多还原

【Abstract】 Objective:Fibrinogen/albumin ratio(FAR)is an easily measurable novel inflammatory index that has been found to be associated with atherosclerosis.In this study,the aim was to assess whether FAR was associated with extent and complexity of coronary artery disease as assessed by the Gensini score and the number of coronary artery lesions,analyze the difference of FAR level in different clinical types of coronary heart disease and its correlation with established systemic inflammatory biomarkers,simultaneously,discuss the usefulness of FAR in predicting GS in patients who suffer from CHD.Methods:This study retrospectively selected 391 CHD patients who were treated for the first time with CAG in the Cardiovascular and Cerebrovascular Branch Hospital,which is affiliated of Yan’an University from January 2020 to January 2021due to chest tightness and other precordial discomfort symptoms.In period of those time,242 Non-CHD controls with negative coronary CTA scans were included.Collect the clinical data,laboratory test indicators,and angiography data of the above research subjects when they are admitted to the hospital,and record them truthfully.Calculate the neutrophil/lymphocyte ratio(NLR)and platelet/lymphocyte ratio(PLR)based on the NEUT,PLT,LY,and high-sensitivity C-reactive protein(hs-CRP)determined by blood routine testing of all patients.Similarly,Calculate the fibrinogen/albumin ratio(FAR)based on the serum fibrinogen(FIB)and albumin(ALB)levels measured in the blood coagulation series of tests.According to the clinical manifestations of patients with precordial discomfort at the time of admission,ECG,myocardial injury,myocardial enzyme spectrum and other auxiliary examination results,as well as the CAG operation records,CHD patients are divided into three groups according to clinical types:stable angina group(SAP group)with95 cases,aged 43 to 86 years old;199 cases in NSTE-ACS group,Aged 47 to 87 years old;97 cases in the STE-ACS group,aged 40 to 83 years old.The CHD patients were divided into low GS group(GS<20 points)108 cases and high GS group(GS≥20points)283 cases with Gensini score(GS)of 20 as the cut-off point.According to the FAR cutoff value of 6.16 when the value of high GS is predicted to be maximum,CHD patients were divided into high FAR group(FAR≥6.16)255 cases,and low FAR group(FAR<6.16)136 cases.Comparative analysis:1.Different clinical type group(SAP group、NSTE-ACS group、STE-ACS group与Non-CHD controls):⑴Differences in basic characteristics of four group patients;⑵Differences in FAR and different inflammatory biomarkers(hs-CRP,NLR,PLR)Whether there were differences among these groups;⑶Comparison of differences with GS among three CHD clinical type groups.2.Spearman correlation analysis analyzes the correlation between FAR and different inflammatory biomarkers(hs-CRP,NLR,PLR).3.FAR and severity of coronary artery disease:⑴In different vascular disease groups,analysis the differences of FAR and different inflammatory biomarkers(FIB,ALB,hs-CRP,NLR,PLR),the same as GS.⑵In low GS group and high GS group.(1)Comparison with differences of general clinical data;(2)Were there a difference among FAR and different inflammatory biomarkers(hs-CRP,NLR,PLR),GS between the low GS group and the high GS group.4.Spearman correlation analysis analyzes the correlation between FAR,different inflammatory biomarkers(hs-CRP,NLR,PLR)and GS in CHD patients.5.The value of FAR in predicting the severity of coronary artery disease and its clinical application:⑴Using binary Logistic regression to analyze Whether FAR,different inflammatory biomarkers(hs-CRP,NLR,PLR)and other related indicators were independent risk factors for high GS.⑵Evaluate the predictive value of FAR and hs-CRP alone and the combination of the two inflammatory biomarkers for high GS by ROC curve.⑶The value of clinical application:comparing the difference of GS and the incidence rate of three-vessel disease and STE-ACS between the high FAR and low FAR group.Result:1.No significant differences were noted in the proportion of males,smokers,patients with hypertension and patients with diabetes mellitus.There were also no significant differences in age,BMI,total cholesterol(TC),and aminotransferase(ALT),creatinine(CRE)among the four groups of different clinical types(above P>0.05);TG levels in three CHD groups were significantly higher than those in non-CHD controls(P<0.05),and there was not significantly different in the three CHD groups compared in pairs(above P>0.05);The level of LDL-C increased gradually with the aggravation of clinical types of coronary artery disease among the four groups.The difference in the level of LDL-C between NSTE-ACS group and STE-ACS group was not noted in statistics(P>0.05),but the difference between the other groups were noted in statistics(P<0.05).The level of HDL-C in CHD group was significantly lower than that in Non-CHD controls,and it was significantly higher in SAP group than that in STE-ACS group(P<0.05).The difference between SAP group and NSTE-ACS group in HDL-C was not noted in statistics(P>0.05),the same as between NSTE-ACS and STE-ACS group.2.The overall trend of FIB and NLR,in each group was:Non-CHD group<SAP group<NSTE-ACS group<STE-ACS group,whereas ALB was Non-CHD group>SAP group>NSTE-ACS group>STE-ACS group.The FAR increased with aggravation of clinical types.The above inflammatory biomarkers are compared among the four groups in pairs,FIB,FAR and NLR although in SAP group were higher than those in Non-CHD controls,ALB was lower,the difference between the two groups was not noted in statistics(P>0.05),the other CHD three group in the inner pairwise comparisons were statistically significant.The level of PLR in STE-ACS group were the highest comparised with the other three groups and the difference respectively were all noted in statistics(above P<0.05),but the difference between the three groups in pairs was not noted in statistics(above P>0.05).The hs-CRP of four groups in the inner pairwise comparisons were noted in statistics(P>0.05).It can be concluded FAR could reflect the degree of inflammatory state and stability of coronary heart disease to a certain extent.3.The trend of GS among the three CHD groups was:SAP group<NSTE-ACS group<STE-ACS group,but there was no statistical difference between the NSTE-AC group and the STE-ACS group.4.Association between variables was detected by Spearman’s correlation analyses between FAR and different inflammatory biomarkers.FAR was positively associated with hs-CRP(rs=0.822),NLR(rs=0.463),PLR(rs=0.296),FAR was significantly associated with hs-CRP.5.FIB,FAR,hs-CRP,NLR and PLR increased with the increase of the number of coronary artery lesions,whereas ALB decreased.Comparison with Single coronary artery lesion group,FIB、FAR and hs-CRP were significantly higher,whereas the difference of ALB was lower significantly in multiple coronary artery lesion group(double coronary artery and triple coronary artery lesion group)(above P<0.05).FIB、FAR、ALB、hs-CRP in multiple coronary artery lesion group were no significant differences(above P>0.05).Comparison with triple vascular lesion group,higher NLR and PLR were significantly different in single and double coronary artery lesion group(above P<0.05),whereas NLR、PLR were not between single and double coronary artery lesion group(P>0.05).GS were significantly different among the three groups,GS of triple coronary artery lesion group was the highest,the second was double coronary artery and in single coronary artery lesion group was minimum,The three groups in the inner pairwise comparisons were noted in statistics(above P<0.05).6.Independent sample T test showed that age,BMI were significantly different between the low GS group and the high GS group.Which were the same as the proportion of males,smokers,patients with hypertension and patients with diabetes mellitus detectde byχ~2test(P>0.05).The comparsion in TC,TG,ALT,CRE were also not noted in statistics(above P>0.05).Comparision with high GS group,higher LDL-C and lower HDL-C were noted in statistics.(above P<0.05).It can be seen that FAR and hs-CRP were better than NLR and PLR in evaluating the number of coronary artery lesions.7.In the high GS group,FIB,FAR,hs-CRP,NLR,PLR were significantly increased(P<0.05),while the ALB level was significantly reduced(P<0.001).8.When analyzing the correlation between each variabies and GS.FAR(rs=0.407),FIB(rs=0.325),hs-CRP(rs=0.394),NLR(rs=0.303),PLR(rs=0.170)were positively correlated with GS;while ALB wasnegatively correlated with GS(rs=-0.333).Obviously,the correlation between FAR and GS was the strongest.9.After binary Logistic regression analysis,FAR,hs-CRP levels were an independent predictor of high GS in patients with CHD(OR=1.274,95%CI:1.035 to 1.567,P=0.022;OR=1.757,95%CI:1.069 to 2.887,P=0.026 respectively).Therefore FAR is significantly related to GS in predicting the severity of coronary artery disease in patients with CHD.10.ROC curve was used to detect the predicted value of different inflammatory biomarkers for GS(≥20).The cut-off level of≥6.16 FAR predicted GS(≥20)[SN76.7%,SP 64.8%,area under curve(AUC)of 0.751,95%CI:0.698 to 0.804,P<0.001),the cut-off level of≥2.41 hs-CRP predicted GS(≥20)(SN 74.9%,SP 64.8%,AUC of0.729 95%CI:0.671 to 0.788,P<0.001).The cut-off level of≥8.66 FAR combined with hs-CRP predicted GS(≥20)(SN 72.8%,SP 68.5%,AUC of 0.761,95%CI:0.708 to0.815,P<0.001).The results revealed that the AUC of FAR was higher comparied with hs-CRP,and the AUC of FAR combined with hs-CRP was the highest in predicting high GS.11.Comparison with low FAR group,the incidence of triple vascular disease and STE-ACS were significantly higher in high FAR group,and the GS was higher similarly(above P<0.05).it suggests when the level of FAR more than 6.16 in those patients,triple coronary artery lesion and STE-ACS are more likely to occur,coronary artery disease is more serious,with the value of clinical application.Conclusion:1.The level of FAR,a novel inflammatory index,increased with the aggravation of clinical types of coronary heart disease,which might help assess the inflammatory load state and the stability of coronary artery lesions in patients with coronary heart disease.2.FAR is positively correlated with other established inflammatory indexes,FAR is correlation with coronary GS,closely related to the severity of coronary artery diseasein patients with coronary heart disease.3.FAR is an independent predictor for high GS,and the application of FAR and hs-CRP can improve the predictive value of high GS.4.FAR is helpful to evaluate the the number and severity of coronary artery lesions in patients with coronary heart disease.It has certain clinical application value.更多还原