摘要
目的研究慢性心力衰竭(CHF)患者血清胶原代谢物Ⅰ型胶原羧基端肽(CITP)和基质金属蛋白酶-1(MMP-1)比值(CITP/MMP-1)水平与心肌纤维化(MF)严重程度相关性及在MF的诊断和预后价值。方法回顾性研究,选取2021年5月18日至2022年2月30日在泰达国际心血管病医院心内科住院并行核磁检查的110例CHF患者,男86例,(56.60±11.15)岁;女24例,(60.06±12.02)岁。应用酶联免疫法检测血清CITP及MMP-1并计算CITP/MMP-1,全自动化学发光分析仪检测血浆脑钠肽(BNP)。采用方差分析及非参数检验比较各组间指标差异,Spearman分析血清胶原代谢物与心肌纤维化严重程度相关性,Logistic回归进行多因素分析,ROC曲线评估相关指标的辅助诊断价值。对患者定期随访,记录出院后1年内主要不良心脏事件,包括心源性死亡、HF再住院、恶性心律失常、心肌梗死。Cox回归分析不良预后的危险因素。对LGE(+)组患者的CITP/MMP-1比值进行中位数分成两组,以及联合BNP、CITP/MMP-1比值进行中位数分组,用Kaplan-Meier进行生存分析,并用Log Rank检验。结果血清MMP-1及BNP在LGE(+)组中高于LGE(-)组(1.79 ng/ml>0.91 ng/ml,Z=-2.924;503 pg/ml>367 pg/ml,Z=-1.932;P均<0.05);CITP/MMP-1比值在LGE(+)组中低于LGE(-)组(3.84<10.85,Z=-3.601,P<0.001)。MMP-1在CHF伴心律失常组中高于CHF组(1.98 ng/ml>1.25 ng/ml,Z=-2.016),CITP/MMP-1比值低于CHF组(3.25<5.73,Z=-2.751),P均<0.05。CHF患者血清CITP/MMP-1比值与MF严重程度成负相关(r=-0.363,P<0.001),BNP、MMP-1与MF严重程度成正相关(r=0.267,r=0.264,P均<0.05)。血清BNP与胶原代谢物MMP-1成正相关,与CITP/MMP-1比值成负相关(P均<0.05)。Logistic多因素回归分析发现,只有CITP/MMP-1是心肌纤维化的预测指标,OR值为0.624(P=0.005)。ROC曲线评估血清BNP、MMP-1及CITP/MMP-1比值对HF患者心肌纤维化的辅助诊断价值,AUC分别0.653、0.696、0.754。比较CITP/MMP-1比值及BNP诊断纤维化价值的ROC曲线的AUC的结果显示,CITP/MMP-1诊断纤维化的准确性优于BNP诊断的准确性,差异有统计学意义(Z=-3.808,P<0.001)。Cox回归分析结果显示CITP/MMP-1≤3.84是不良预后的危险因素,OR=2.647(P=0.009)。1年内随访Kaplan-Meier生存分析结果显示CITP/MMP-1比值较低的一组的存活率明显低于较高组(P=0.014)。联合BNP、CITP/MMP-1比值的Kaplan-Meier生存分析结果显示CITP/MMP-1升高及BNP降低组存活率高于CITP/MMP-1比值降低及BNP升高组(P=0.011)。结论CITP/MMP-1比值可作为交联程度的负相关指标,该比值在MF评估中优于BNP,对慢性心衰患者心肌纤维化有较好的辅助诊断价值,有望成为慢性心衰患者保护性指标并用于临床心肌纤维化评估。CITP/MMP-1比值与主要不良心脏事件发生率相关,CITP/MMP-1≤3.84可作为CHF患者预后心血管不良事件的预测因子。
Objective To investigate the association between CITP/MMP-1 ratio and the severity of Myocardial fibrosis(MF)in patients with Chronic Heart failure(CHF)and its diagnostic and prognostic value in patients with MF.Methods A retrospective study was conducted to select 110 cases[86 males,(56.60±11.15)years old;24 females,(60.06±12.02)years old]who were hospitalized in the Department of Cardiology,Teda International Cardiovascular Hospital from May 18,2021 to February 30,2022 and underwent magnetic magnetic examination.Serum CITP and MMP-1 were detected by enzyme-linked immunoassay and CITP/MMP-1 ratio was calculated.Plasma brain natriuretic peptide(BNP)was detected by automatic chemiluminescence analyzer.Anova and non-parametric test were used to compare the difference of indexes among all groups.Spearman analysis was used to analyze the correlation between serum collagen metabolites and the severity of myocardial fibrosis.Logistic regression analysis was performed for multivariate analysis,and ROC curve was used to evaluate the auxiliary diagnostic value of related indexes.Major adverse cardiac events within 1 year after discharge were recorded,including cardiogenic death,HF rehospitalization,malignant arrhythmia,and myocardial infarction.The risk factors of poor prognosis were analyzed by Cox regression.Patients were divided by the median value of CITP/MMP-1 ratio or the median value of CITP/MMP-1 ratio and BNP.Survival analysis was performed by Kaplan-Meier and Log Rank test was performed.Results Serum MMP-1 and BNP in LGE(+)group were higher than those in LGE(-)group(1.79 ng/ml>0.91 ng/ml,Z=-2.924;503 pg/ml>367 pg/ml,Z=-1.932;P<0.05);The CITP/MMP-1 ratio in the LGE(+)group was lower than that in the LGE(-)group(3.84<10.85,Z=-3.601,P<0.001).MMP-1 in CHF with arrhythmia group was higher than that in CHF group(1.98 ng/ml>1.25 ng/ml,Z=-2.016),while CITP/MMP-1 ratio was lower than that in CHF group(3.25<5.73,Z=-2.751),all P<0.05.CITP/MMP-1 ratio in CHF patients was negatively correlated with the severity of MF(r=-0.363,P<0.001),and BNP and MMP-1 were positively correlated with the severity of MF(r=0.267,r=0.264,P<0.05).Serum BNP was positively correlated with collagen metabolite MMP-1 and negatively correlated with CITP/MMP-1 ratio(all P<0.05).Logistic multivariate regression analysis showed that only CITP/MMP-1 was a predictor of myocardial fibrosis,with an OR value of 0.624(P=0.005).ROC curve was used to evaluate serum BNP,MMP-1 and CITP/MMP-1 ratio in the diagnosis of myocardial fibrosis in HF patients,with AUC of 0.653,0.696 and 0.754,respectively.The accuracy of CITP/MMP-1 ratio in diagnosing fibrosis was better than that of BNP by comparing their AUC,and the difference was statistically significant(Z=-3.808,P<0.001).Cox regression analysis showed that CITP/MMP-1≤3.84 was a risk factor for poor prognosis,OR=2.647(P=0.009).Kaplan-Meier survival analysis at 1-year follow-up showed that the survival rate of the group with lower CITP/MMP-1 ratio was significantly lower than that of the group with higher CITP/MMP-1 ratio(P=0.014).The survival rate of CITP/MMP-1 increased and BNP decreased group was higher than that of CITP/MMP-1 decreased and BNP increased group(P=0.011).Conclusions The ratio of CITP/MMP-1 can be used as a negative correlation indicator of the degree of cross-linking,which is better than BNP in the evaluation of MF,and has a good auxiliary diagnostic value for myocardial fibrosis in patients with chronic heart failure,and is expected to become a protective indicator for patients with chronic heart failure and be used in clinical evaluation of myocardial fibrosis.CITP/MMP-1 ratio is associated with the incidence of major adverse cardiac events,and CITP/MMP-1≤3.84 can be used as a predictor of prognostic adverse cardiovascular events in CHF patients.
作者
刘雨庭
郭维丽
杜桂迎
周田
韩雪晶
贾茗宇
范丽娟
贾克刚
Liu Yuting;Guo Weili;Du Guiying;Zhou Tian;Han Xuejing;Jia Mingyu;Fan Lijuan;Jia Kegang(Clinical School of Cardiovascular Disease,Tianjin Medical University,Tianjin 300457,China;Department of Clinical Laboratory,Xi′an Children′s Hospital,Xian 710100,China;Department of Radiology,Teda International Cardiovascular Hospital,Tianjin 300457,China;Department of Clinical Laboratory,Teda International Cardiovascular Hospital,Tianjin 300457,China;School of Imaging,Suzhou University Medical School,Suzhou 215006,China)
出处
《中华检验医学杂志》
CAS
CSCD
北大核心
2023年第12期1259-1267,共9页
Chinese Journal of Laboratory Medicine
基金
天津市泰达国际心血管病医院院级项目(2022-TD-010)
天津市滨海新区卫生健康委科技项目(2022BWKZ002)。
