血清白介素6、空腹血糖水平与冠心病及不良心血管事件关系的研究

Study on the Correlation of Serum Interleukin-6 and Fasting Blood Glucose with Coronary Heart Disease and Adverse Cardiovascular Events

背景冠心病(CHD)是全世界的主要公共卫生负担之一。虽然已经制订了相应治疗策略,但CHD仍然是全球人口发病和死亡的主要原因。CHD诊断主要依靠冠状动脉造影或冠状动脉增强CT,然而基层医院设备不足,早期诊断及对预后的判断相对困难,故寻找相对简便、易获得的实验室指标,有利于为基层医生诊治CHD提供依据。目的探讨血清白介素6(IL-6)、空腹血糖(FPG)水平与CHD患者冠状动脉狭窄程度、临床分型、病变支数及不良心血管事件的关系。方法纳入2020年9—11月就诊于新疆医科大学第五附属医院的CHD患者为研究对象,收集患者的一般资料与实验室检查结果。依据Gensini积分评分标准,将患者得分结果按中位数分为轻度狭窄组(A组,Gensini积分≤33.25分,n=40)和中重度狭窄组(B组,Gensini积分>33.25分,n=40)。根据冠状动脉造影结果,将患者按照病变支数分为单支病变组(n=28)、双支病变组(n=21)及多支病变组(病变支数≥3,n=31)。根据患者临床分型,将患者分为稳定型心绞痛组(n=34)和急性冠状动脉综合征组(n=46)。采用Spearman秩相关分析探索血清IL-6、FPG与患者相关资料的关系。采用Kaplan-Meier法绘制患者的生存曲线,生存曲线的比较采用Log-rank检验。采用单因素及多因素Cox比例风险模型探究CHD患者不良心血管事件发生风险的影响因素。绘制IL-6预测不良心血管事件发生的受试者工作特征曲线(ROC曲线)。结果A组IL-6、FPG水平低于B组,多支病变组IL-6水平高于单支病变组,FPG水平高于双支病变组,急性冠状动脉综合征组IL-6、FPG水平高于稳定型心绞痛组,差异有统计学意义(P<0.05)。Spearman秩相关分析结果显示,血清IL-6水平与临床分型、冠状动脉病变支数、Gensini积分、性别、三酰甘油(TG)、FPG有相关性,FPG水平与临床分型、冠状动脉病变支数、Gensini积分、年龄、IL-6水平有相关性(P<0.05)。按IL-6中位表达水平(45.8 ng/L)将患者分为IL-6>45.8 ng/L组(n=39)和IL-6≤45.8 ng/L组(n=41),FPG以参考值上限(6.1 mmol/L)作为分组标准,将患者分为FPG>6.1 mmol/L组(n=36)和FPG≤6.1mmol/L组(n=44)。Log-rank检验结果显示,IL-6>45.8 ng/L组不良心血管事件发生率高于IL-6≤45.8 ng/L组(76.9%与36.6%;χ^(2)=16.075,P<0.001)、FPG>6.1 mmol/L组不良心血管事件发生率高于FPG≤6.1 mmol/L组(69.4%与45.5%;χ^(2)=4.292,P=0.038)。多因素Cox比例风险模型结果显示IL-6是患者发生不良心血管事件的影响因素(HR=2.396,95%CI=1.203~6.054,P<0.05)。IL-6预测患者发生不良心血管事件的ROC曲线下面积为0.769(95%CI=0.658~0.880),最佳截断值为40.97 ng/L,灵敏度为0.867,特异度为0.683。结论血清IL-6、FPG水平与CHD及其不良预后相关,血清IL-6是CHD患者不良心血管事件发生风险的独立危险因素。

Background Coronary heart disease(CHD)is one of the major public health burdens in the world.Although treatment strategies have been developed,but CHD remains a leading cause of morbidity and mortality worldwide.The diagnosis of CHD mainly relies on coronary angiography or contrast-enhanced computed tomography.However,due to the lack of equipment in primary hospitals,early diagnosis and prognosis judgment are relatively difficult.Therefore,the search for relatively simple and easy-to-obtain laboratory indicators is conducive to providing basis for primary care physicians to diagnose and treat CHD.Objective To investigate the correlation of serum interleukin-6(IL-6)and fasting blood glucose(FPG)levels with the degree and clinical classification of coronary stenosis,number of lesions and adverse cardiovascular events in patients with CHD.Methods CHD patients admitted to the Fifth Affiliated Hospital of Xinjiang Medical University from September to November 2020 were included as the study objects,and their general data and laboratory test results were collected.According to Gensini score criteria,the patients were divided into the mild stenosis group(group A,Gensini score≤33.25 points,n=40)and moderate and severe stenosis group(group B,Gensini score>33.25 points,n=40)based on the Gensini scoring criteria.According to the results of coronary angiography results,patients were divided into the single-vessel lesion group(n=28),double-vessel lesion group(n=21)and multi-vessel lesion group(number of lesion branch≥3,n=31)based on the number of lesions.According to the clinical classification,patients were divided into stable angina group(n=34)and acute coronary syndrome group(n=46).Spearman rank correlation analysis was used to explore the relationship of serum IL-6,FPG with relevant data of patients.Survival curves of patients were plotted using the Kaplan-Meier method,and the comparison of survival curves was performed by Log-rank test.Univariate and multivariate Cox proportional hazard regression analyses were used to explore the factors influencing the risk of adverse cardiovascular events in patients with CHD.The receiver operating characteristic(ROC)curve of IL-6 predicting the occurrence of adverse events was plotted.Results IL-6 and FPG in group A were lower than those in group B,IL-6 in the multi-vessel lesion group was higher than that in the single-vessel lesion group,FPG was higher than that in double-vessel lesion group,and IL-6 and FPG in acute coronary syndrome group was higher than that in stable angina group,with statistical significance(P<0.05).Spearman rank correlation analysis showed that serum IL-6 was correlated with clinical type,number of coronary lesions,Gensini score,gender,triglyceride(TG)and FPG,and FPG was correlated with clinical type,number of coronary lesions,Gensini score,age and IL-6(P<0.05).The patients were divided into IL-6>45.8 ng/L group(n=39)and IL-6≤45.8 ng/L group(n=41)according to the median IL-6 expression level(45.8 ng/L),and the upper limit of normal FPG(6.1 mmol/L)was used as the grouping standard to divide the patients into FPG>6.1 mmol/L group(n=36)and FPG≤6.1 mmol/L group(n=44).Log-rank test results showed that the incidence of adverse cardiovascular events in IL-6>45.8 ng/L group was higher than that in IL-6≤45.8 ng/L group(76.9%vs.36.6%;χ^(2)=16.075,P<0.001),FPG>6.1 mmol/L group had a higher incidence of adverse cardiovascular events than FPG≤6.1 mmol/L group(69.4%vs.45.5%;χ^(2)=4.292,P=0.038).Multivariate Cox proportional hazard regression analysis showed that IL-6 was a significant factor in adverse cardiovascular events in patients with CHD(HR=2.396,95%CI=1.203-6.054,P<0.05).The area under ROC curve of IL-6 for predicting adverse cardiovascular events was 0.769(95%CI=0.658-0.880),the best optimal value was 40.97 ng/L,with the sensitivity and specificity of 0.867 and 0.683.Conclusion Serum IL-6 and FPG levels are associated with CHD and its poor prognosis.Serum IL-6 is an independent risk factor for adverse cardiovascular events in patients with CHD.