慢性心力衰竭患者血清可溶性ST2、基质金属蛋白酶2、基质金属蛋白酶9水平变化及其与心血管事件的关系研究

Changes of Serum Levels of sST2,MMP-2,MMP-9 and Their Relations to Cardiovascular Events in Patients with Chronic Heart Failure

背景慢性心力衰竭(CHF)是多种心血管疾病的终末期表现,寻找可靠的生物学标志物以快速、准确地预测心力衰竭患者心血管事件发生风险具有重要临床意义。目的分析CHF患者血清可溶性ST2(sST2)、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)水平变化及其与心血管事件的关系。方法选取2016年2月-2018年6月四川大学华西广安医院收治的CHF患者96例作为CHF组,另选取30例同期体检的健康志愿者作为对照组;根据随访期间心血管事件发生情况将CHF患者分为A组(发生心血管事件,n=36)和B组(未发生心血管事件,n=60)。比较对照组与CHF组受试者、不同纽约心脏病协会(NYHA)分级CHF患者血清sST2、MMP-2及MMP-9水平,并比较A组及B组患者一般资料、血红蛋白、血钠、肾小球滤过率、左心室射血分数(LVEF)及血清N末端脑钠肽前体(NT-proBNP)、sST2、MMP-2、MMP-9水平;CHF患者心血管事件的影响因素分析采用多因素Logistic回归分析;绘制ROC曲线以评价LVEF及血清NT-proBNP、sST2、MMP-2、MMP-9水平对CHF患者心血管事件的预测价值。结果(1)CHF组患者血清sST2、MMP-2及MMP-9水平高于对照组(P<0.05)。(2)NYHA分级Ⅲ、Ⅳ级CHF患者血清sST2、MMP-2及MMP-9水平高于NYHA分级Ⅱ级,NYHA分级Ⅳ级CHF患者血清sST2、MMP-2及MMP-9水平高于NYHA分级Ⅲ级(P<0.05)。(3)随访期间CHF组患者心血管事件发生率为37.5%(36/96);A组与B组患者性别,年龄,高血压、糖尿病、冠心病发生率,心率,收缩压,使用β-受体阻滞剂、血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂(ACEI/ARB)者所占比例,血红蛋白,血钠比较,差异无统计学意义(P>0.05);A组患者肾小球滤过率及LVEF低于B组,血清NT-proBNP、sST2、MMP-2及MMP-9水平高于B组(P<0.05)。(4)多因素Logistic回归分析结果显示,LVEF〔OR=1.208,95%CI(1.043,1.399)〕及血清NT-proBNP〔OR=1.332,95%CI(1.087,1.634)〕、sST2〔OR=1.560,95%CI(1.059,2.300)〕、MMP-2〔OR=1.385,95%CI(1.037,1.852)〕及MMP-9〔OR=1.461,95%CI(1.208,1.767)〕水平是CHF患者心血管事件的影响因素(P<0.05)。(5)ROC曲线显示,LVEF及血清NT-proBNP、sST2、MMP-2、MMP-9水平预测CHF患者心血管事件的曲线下面积分别为0.668、0.671、0.819、0.760、0.782。结论 CHF患者血清sST2、MMP-2及MMP-9水平明显升高且与心功能有关,三者均是CHF患者心血管事件的影响因素且对心血管事件的预测价值较高。

Background Chronic heart failure(CHF)is the end-stage manifestations of various cardiovascular diseases,thus it is of great clinical significance to find reliable markers to quickly and accurately predict the risk of cardiovascular events.Objective To analyze the changes of serum levels of sST2,MMP-2,MMP-9 and their relations to cardiovascular events in patients with CHF.Methods From February 2016 to June 2018,a total of 96 patients with CHF were selected as CHF group in West China Guang’an Hospital of Sichuan University,meanwhile 30 healthy volunteers admitted to this hospital for physical examination were selected as control group;patients with CHF were divided into A group(complicated with cardiovascular events,n=36)and B group(did not complicate with cardiovascular events,n=60)according to the incidence of cardiovascular events during follow-up.Serum levels of sST2,MMP-2 and MMP-9 were compared between control group and CHF group,in CHF patients with different NYHA grades;general information,hemoglobin,serum natrium,GFR,LVEF,serum levels of NT-proBNP,sST2,MMP-2 and MMP-9 were compared between A group and B group;influencing factors of cardiovascular events in patients with CHF were analyzed by multivariate Logistic regression analysis;ROC curve was drawn to evaluate the predictive value of LVEF,serum levels of NT-proBNP,sST2,MMP-2 and MMP-9 on cardiovascular events in patients with CHF.Results(1)Serum levels of sST2,MMP-2 and MMP-9 in CHF group were statistically significantly higher than those in control group(P<0.05).(2)Serum levels of sST2,MMP-2 and MMP-9 in CHF patients with Ⅲ-and Ⅳ-NYHA grade were statistically significantly higher than those in CHF patients with Ⅱ-NYHA grade,serum levels of sST2,MMP-2 and MMP-9 in CHF patients with Ⅳ-NYHA grade were statistically significantly higher than those in CHF patients with Ⅲ-NYHA grade(P<0.05).(3)Incidence of cardiovascular events in CHF group was 37.5%(36/96)during follow-up;there was no statistically significant difference in gender,age,incidence of hypertension,diabetes or coronary heart disease,heart rate,SBP,proportion of patients using β-receptor blockers or ACEI/ARB,hemoglobin or serum natrium between A group and B group(P>0.05);GFR and LVEF in A group were statistically significantly lower than those in B group,while serum levels of NT-proBNP,sST2,MMP-2 and MMP-9 were statistically significantly higher than in B group(P<0.05).(4)Multivariate Logistic regression analysis results showed that,LVEF〔OR=1.208,95%CI(1.043,1.399)〕,serum levels of NT-proBNP〔OR=1.332,95%CI(1.087,1.634)〕,sST2〔OR=1.560,95%CI(1.059,2.300)〕,MMP-2〔OR=1.385,95%CI(1.037,1.852)〕and MMP-9〔OR=1.461,95%CI(1.208,1.767)〕were influencing factors of cardiovascular events in patients with CHF(P<0.05).(5)ROC curve showed that,AUC of LVEF,serum levels of NT-proBNP,sST2,MMP-2 and MMP-9 in predicting cardiovascular events in patients with CHF was 0.668,0.671,0.819,0.760 and 0.782,respectively.Conclusion Serum levels of sST2,MMP-2 and MMP-9 are significantly elevated and related to cardiac function in patients with CHF,and the above three are influencing factors of cardiovascular events in patients with CHF,with relatively high predictive value on cardiovascular events.