Prognostic Value Of N-terminal B-type Natriuretic Peptide And Big Endothelin-1 In Patients With Severe Heart Failure And The Relationship Between Both Markers And Atrial Fibrillation And Pulmonary Artery Hypertension

Background:B-type natriuretic peptide(BNP) is a important neurohormone,it has a number of systemic effects,including vasodilation,increases in urinary volume and sodium output,and inhibition of the sympathetic nervous system and the renin-angiotensin-aldosterone system.N-terminal fragment of BNP is NT-proBNP,BNP and NT-proBNP are released in blood in equal molar manner.NT-proBNP is inactive,but its level of plasma is significantly increased in patients with heart failure,and its increased levels is significantly related with severity of heart failure(HF), as well as prognosis of HF.Endothelin(ET) is another important member in neurohormone family.Endothelin-1(ET-1) is a strong pressor.The biological precursor of ET is big endothelin-1(big ET-1).It is reported that the plasma concentration of ET-1 is significantly increased in patients with HF and the increased level is correlated with severity of HF and prognosis.The increased plasma levels of ET-1 in HF patients are owed mainly to an increase in the concentration of big ET-1.However,it is not clear that the prognostic significance of NT-proBNP and big ET-1 for Chinese patients with severe HF and the relationship between NT-proBNP or big ET-1 and cardiovascular diseases.This study may provide evidences for the clinical application of NT-proBNP and big ET-1 in patients with severe HF. Objective:To investigate the the clinic application of plasma levels of NT-proBNP and big ET-1 in severe HF patients,especially their clinical significance in prognosis of short term and in different type of cardiovascular diseases combining with severe HF.Methods:We analyzed in 132 patients with severe HF(New York Heart Association[NYHA]classⅢtoⅣ,age 24-80 years,male 83 female 49,ejection fraction 13%-66%),Plasma concentration of NT-proBNP and big ET-1 were measured by enzyme-linked immunosorbent assay(ELISA) and the level of high sensitivity C-reactive protein(hsCRP) were measured by immmunoturbidimetry.These data were compared with 132 healthy subjects(age 22-82 years,male 79 female 53),investigating cardiac events in HF patients leaving hospital in half a year.Results:The plasma NT-proBNP concentrations and big ET-1 concentrations of HF patients were significantly higher than those of the normal controls (P=0.000,P=0.000),and they showed significant positive correlations with NYHA functional classification(P=0.024,P=0.021).LgNT-proBNP showed positive correlation with big ET-1(r=0.(?),P=0.000)and negative correlation with LVEF(r=-0.(?),P=0.0(?)).According to HF patients combining with or without Af or PAH,the plasma big ET-1 concentration showed significant differences between two groups (P=0.022,P=0.000).Applying plasma big ET-1 concentration to diagnose HF combining with PAH,ROC showed that area under curve was 0.742 (95%CI:0.653-0.832,P=0.000),when cutoff value was 4.09fmol/ml,the sensitivity and the specificity were 71.4%and 67.8%respectively.After a follow-up of 6 months,there were 20 deaths and 25 readmission in the 132 HF patients.On a COX proportional hazards analysis,including these biochemical markers,age,sex,functional class,LVEF, LgNT-proBNP,big ET-1,NT-proBNP was the independent predictor of cardiac events,RR were 5.297(95%CI:2.071～13.545,P=0.001),and only NT-proBNP was the independent predictor of death,OR were 13.672 (95%CI:2.587～72.253,P=0.002).big ET-1,LVEF,LVEDD were not independently predictive of cardiac events.Conclusions:NT-proBNP showed positive correlation with big ET-1.The plasma big ET-1 concentrations may be assistant to diagnose HF patients with PAH.NT-proBNP,but not big ET-1 is independently predictive of cardiac events in patients with severe HF leaving hospital in half a year. Measurement of NT-proBNP in patients with severe HF is beneficial to identify patients at higher risk for cardiac events.