The Level Of Serum IGFBP7 In Heart Failure Patients With Preserved Ejection Fraction And Its Clinical Significance

Background:Heart failure(HF)is a complex clinical syndrome caused by any structural and/or functional cardiac abnormality,resulting in ventricular systolic and/or diastolic dysfunction,namely impairment of ventricular filling and/or ejection of blood.The cardinal manifestations of HF are dyspnea and fatigue,which may limit exercise tolerance,and fluid retention,which may lead to pulmonary and/or splanchnic congestion and/or peripheral edema.The main function of heart is ventricular pumping of blood by its contraction,therefore,left ventricular ejection fraction(LVEF)is considered important in classification of patients with HF.It comprises heart failure with reduced ejection fraction(HFrEF),heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF).HFpEF affects approximately half of patients with the clinical syndrome of HF.The prevalence of HFpEF continues to rise(at about 10%per ten year).It may become the predominant phenotype of heart failure in the future.However,there has been no such parallel progress with diagnosis and therapy for HFpEF compared to HFrEF.The underlying reasons for this clinical conundrum are incompletely understood for the pathophysiology of HFpEF,lacking of uniform diagnosis criteria and the heterogeneity of the broad HFpEF patient population.Taken together,HFpEF is a major global public health issue.The search for a rapid,simple and repeated biomarker for HFpEF has important clinical value,which is not only helpful to clarify the pathophysiological mechanism,but also helpful for early diagnosis,assessment,prediction of cardiovascular event risk and guidance of treatment decision.Insulin-like growth factor binding protein 7(IGFBP7)is a soluble and secretory glycoprotein expressed in multiple normal tissues and belongs to the IGFBP family.This protein has been associated with many physiologic processes,including cell proliferation,adhesion,senescence,apoptosis,and angiogenesis,and it is known to be a tumor suppressor in multiple malignancies.In recent years,studies have shown that elevated serum IGFBP7 levels are associated with insulin resistance and the risk of metabolic syndrome.IGFBP7 has been identified as a biomarker associated with cardiac hypertrophy and HF through systematic proteomic candidate searches.Follow-up studies have identified that IGFBP7 serves as a potential biomarker for left ventricular diastolic dysfunction in HFpEF patients and is associated with the prognosis of HF.However,the correlation between IGFBP7 and HFpEF is rarely reported in China.This study aims to analyse the changes of serum IGFBP7 in HFpEF patients and its clinical significance,so as to provide valuable reference for clinical diagnosis and treatment decision of HFpEF.Objective:Through the detection of serum IGFBP7 of HFpEF and patients with normal left ventricular diastolic and systolic function,this study observes the level of serum IGFBP7 in HFpEF patients,and analyzes the relationships between serum IGFBP7 levels and parameters of left ventricular diastolic function and exercise tolerance in patients with HFpEF,and may provide a new idea for early diagnosis and targeted therapy of HFpEF.Methods:A prospective study was conducted among 50 patients with HFpEF(HF group),30 patients with normal left ventricular diastolic and systolic function(control group)in the Fifth Affiliated Hospital of Zhengzhou University from December 2018 to March 2019.Patients in HF group were categorized into 3 subgroups according to New York Heart Association functional classification:class Ⅰ subgroup,class Ⅱ subgroup,class Ⅲ subgroup.Serum levels of IGFBP7 were detected by enzyme linked immunosorbent assay(ELISA),and N-terminal pro-brain natriuretic peptide(NT-proBNP)was measured by chemi-lumin escence assay.The concentrations of biomarkers were compared between the two groups.Cardiac structure and function were assessed by transthoracic echocardiography,exercise tolerance was assessed by cardiopulmonary exercise testing(CPET).All analyses were performed using SPSS 17.0 statistical software and all P values are two-sided with results<0.05 considered significant.Results:Serum levels of IGFBP7 showed abnormal distribution in the two groups.The concentrations of IGFBP7 in HF group was significantly higher than control group[median 62.52(55.54～69.77)vs.50.81(42.68～52.11),P<0.001].Levels of NT-proBNP were higher among HFpEF patients when compared with those in control group[median 252.35(153.75～329.25)vs.109.30(92.33～148.00),P<0.001].In multivariable analysis,NT-proBNP and IGFBP7 were independently associated with HFpEF(all P<0.05).The area under receiver operating characteristic curve(AUC)of IGFBP7 and NT-proBNP for the diagnosis of HFpEF were 0.801 and 0.865 respectively(all P<0.001).The serum concentrations of IGFBP7 increased with the increase of cardiac function grade,and IGFBP7 levels were significantly different in different New York Heart Association class patients with HFpEF(all P<0.05).IGFBP7 levels were correlated with NT-proBNP and echocardiographic parameters of diastolic function including mitral inflow peak early filling velocity(E),E/mitral inflow peak late diastolic filling velocity(E/A),E/early diastolic mitral annular velocity(E/e’),left atrial volume index(LAVi)and estimated right ventricular systolic pressure(RVSP)[all P<0.05].Compared to control group,HFpEF patients displayed lower peak oxygen uptake(peak VO2)and anaerobic threshold(AT).Furthermore,IGFBP7 concentrations were also significantly associated with parameters of functional capacity such as peak VO2 and AT[all P<0.05].Conclusions:Serum IGFBP7 and NT-proBNP could serve as satisfactory biomakers for HFpEF diagnosis.The serum concentration of IGFBP7 in patients with HFpEF may reflect HF severity.Serum IGFBP7 may be a potential biomarker of HFpEF.A rise in IGFBP7 may reflect worsening diastolic function and reduced exercise tolerance.Therefore,the detection of serum IGFBP7 would be of value to assist with the early diagnosis and further understanding of the pathophysiology and mechanism of HFpEF,and possibly even the optimal treatment strategies for patients who suffer from this complex condition.