Study The Expression Of Plasma STWEAK And Prognosis In Patients With Chronic Heart Failure

BACKGROUNDHeart failure is started by myocardial injury, and then the function and structure of heart are changed. Impaired left ventricular fraction and filling lead to a complicated clinical syndrome (such as dyspnea, weakness and decreased exercise tolerance). Heart failure is the end stage of various kinds of cardiovascular diseases whose disability and mortality are still high. Along with the human society’s development the life span of human beings has been significantly prolonged. Heart failure has become one of the major threats to the public health of the world. Ventricular remodeling is important fundament of heart failure development. How to prevent or reserve ventricular remodeling is important. Much of recent reseach has focused on tumor necrosis factor superfamily and interlenkin family. TWEAK Tumor necrosis factor-like weak inducer of apoptosis is a new member of tumor necrosis factor superfamily. And to de found more powerful in heart failure.In 1997, a cDNA about 1.3kb long similar to tumor necrosis factor (TNF) superfamily was extracted from human tonsils and fetal liver cDNA library. Then it was named after TWEAK, and carried on 17q13 chromosome. Fibroblast growth factor-inducible 14(Fn14) is one acceptor of TWEAK. When TWEAK binds to Fn14, they take part in the development of heart failure. It is the smallest member of tumor necrosisi superfamily so far. CD 163, a scavenger receptor on monocytes and macrophages, also can bind to TWEAK. Its molecular weight is 130000 and rich in cysteine. Maybe the function of CD 163 is to clean TWEAK.In subsequent experiments, researchers found TWEAK was involved in many cellular activities, for instance, proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. It has been proved that TWEAK/Fn14 can lead to myocardial proliferation, hypertrophy, myocardial instistital fiobrosis and activated inflammation cells using animal experiments and cell culture in vitro. There is less clinical research on heart falure, and the some conclusion is controvesal. The levels of TWEAK expression in acute and chronic heart failure showed significant difference, the prognosis has a contradiction conclusion too.The goal of this study was to see the expression of plasma sTWEAK levels in patients with different causes of chronic heart failure (CHF) and healthy controls. Then to explore the relationships between plasma sTWEAK levels with other clinical indexes. To evaluate plasma sTWEAK levels’ short-term prognosis value in chronic heart failure patients.OBJECTIVEThe experiment was to see the expression of plasma sTWEAK levels in patients with different causes of chronic heart failure and healthy controls. To explore the relationship between plasma sTWEAK levels with other clinical indexes. To evaluate plasma sTWEAK levels’ short-term prognosis value in chronic heart failure patients.SUBJECTS & METHODS1. SubjectsFrom January 2013 to August 2014, a total of 212 patients with chronic heart failure and 29 healthy persons who attended Guangzhou General Hospital of Guangzhou Military Region were divided into CHF group and control group.1.1 Inclusion criteria of CHF group①The patients should according with the prognosis of chronic heart failure or left ventricular enlargement ejection fraction decreased;②had clear cause of chronic heart failure; ③≥ 18 years old, all genders;④ regular treatment at least 1 month.1.2 Exclusion standard of CHF group①Patients with malignant or inflammatory diseases, acutely decompensated heart failure, a history of organ transplantation, or significant renal or hepatic failure were excluded; ② One month prior to admission patients had a acute coronary event (unstable angina pectoris, acute ST segement elevation myocardial infarction, acute non ST segement elevation myocardial infarction);③ Some diseases or condition may affect the expression of sTWEAK. Such as autoimmune diseases or taking immunosuppressants, acute necrotizing diseases, acute or chronic infectious diseases (septicopyemia, bacterial infection), clotting hemorrhagic or hemolytic disease, peripheral arterial disease.1.3 Control groupHearthy persons must take detailed interrogation, adequant medcal checkout and labotary examination. Who got heart diseases or other system diseases can not inclused.2. Designe2.1 Assement the expression of sTWEAK in CHF group and control group.2.2 The CHF patients who got only one cause were divided into some sub-groups (hypertension CHF group, coronary heart disease chf group and dilated cardiomyopathy CHF group. then assessment the expression of sTWEAK in these patients’.2.3 To explore the relationship between plasma sTWEAK levels and heart classification.2.4 The CHF patients were divided into high sTWEAK level group and low sTWEAK level by the ROC cutoff point. And explore the prognosis value of sTWEAK in CHF patients.2.5 Follow-up① The follow-up time was 3 month. All the CHF were visited by phone call or in the outpatient departments. ②The content of the follow-up forms was mainly from the general information of patients (gender, age, occupation, medication, regular recertification, compliance, blood pressure, blood fat, glucose, weight, smoking, drink, exercise tolerance, rehospitalization) and some new events(such as new renal function failure, new stroke and new atrial fibrillation).③ Starting event:Time of CHF discharged from hospital.④ The end event was adverse events, such as cardiac death, acute decompensated heart failure, acute myocardial infarction and unstable angina pectoris.⑤Censored value was a time that there was not the end events happened during follow-up period. ⑥ The interval from discharged until onset adverse events was defined time to recurrence of cardiovascular events.3. Methods3.1 Blood samplePlasma samples were obtained in the morning of the next day of admission before intake of medication from a drying pipe. Plasma samples were performed by centrifugation at 1000r/min for 15 min at 4℃ within 30 min of collection. Drying pipes were stored at -80℃ until analysis.3.2Plasma sTWEAK levels’ testingPlasma sTWEAK levels were measured with commercially available ELISA (Cloud-Clone corporation, the USA, test kit batch number:L140417513) according to the manufacturers’ instructions.3.3 Clinical indexesOther blood indexes (total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, hyper-sensitive C reactive protein, blood glucose, urea nitrogen, creatine) were measured by standard laboratory methods in a certified laboratory. The data of left ventricular end diastolic and left ventricular ejection fraction were got from all the entrants’ heart ultrasound results.4. Statistical and analysisSPSS software version 13.0 was used for the statistical analyses. Data are reported as mean Χ±SD. The independent Student’s t-test or Mann Whitney U test was used to assess the data and Levene’s test was used to evaluat the equality of variances. One way ANOVA were applied in sub-group. Kruscal wallis test were prepared for the unequal variances. Enumeration data were chi-square test. The correlations of variances were examined by Spearman’s correlation coefficient. To determine cutoff value of sTWEAK in CHF patients by using receiver operating characteristic curve (ROC curve). Then all the patients were divided into two groups (plasma sTWEAK of high level group and low level group). The risk of cardiovascular events in patents with CHF was determined by Kaplan-Meier analysis. Survival curve was compared with long rank test. The rate of adverse events between plasma sTWEAK of high level group and low level group was determined by chi-square test. The significant level equaled to 0.05. P<0.05 meant statistical signification.RESULTS1. The density of sTWEAK in plasma of the CHF group was 195.75±72.62 pg/ml, which of the control group was 355.26±22.75 pg/ml. There was significant difference between the density of sTWEAK in plasma of the CHF group and the control group (P=0.000). Within the CHF group, no significant difference was shown between male-female (P=0.310) and patients younger than 60-older than 60(P=0.074).The density of sTWEAK in plasma of NYHA Ⅰ,Ⅱ,Ⅲ group were 196.1±75.1 pg/ml、175.7±65.3 pg/ml、207.0±699.3 pg/ml. There was no significant difference among the three groups.howerve, BNP and Hs-crp showed siginificant different.2. The density of sTWEAK in plasma of the hypertension CHF group, coronary heart disease CHF group and dilated cardiomyopathy CHF group were 167.80±40.83 pg/ml,148.48±63.8 pg/ml,273.41±39.46 pg/ml in sequence. Levels of sTWEAK in dilated cardiomyopathy CHF group is higher then hypertension CHF group and coronary heart disease CHF group (P=0.000), The plasma sTWEAK levels between hypertension group and coronary heart disease group showed no significant difference (P=0.043),.3. The plasma sTWEAK level was positive correlated with left ventricular end diastolic diameter, BNP, high sensitivity C-reactive protein and glycosylated hemoglobin.4. Evaluate the prediction of the plasma sTWEAK level for adverse events. The AUC of the ROC curve was 0.611 (P=0.047), the cut off was 192.14 pg/ml, of which the sensitivity and specificity were 0.563 and 0.668.the rate of cardiovascular events was higher in high plasma sTWEAK level than in low level(Χ2=6.136, P=0.013).5. In high plasma sTWEAK level group, the average time of adverse events was 79.841±2.290 day, and in low plasma sTWEAK level group was 84.955±1.387 day. The high plasma sTWEAK level patients would had higher risk for adverse events than the low plasma sTWEAK level patien (Log-rank Χ2=5.979, P=0.014)CONCLUSIONS1. The plasma sTWEAK level in CHF patients is significant lower then the healthy’, basic diseases may influence the expression of sTWEAK.2. The plasma sTWEAK level was correlated with index for left ventricular function, such as BNP. But,it has little function of assessment the severity of CHF patients.3. The plasma sTWEAK level in CHF patients may has a predictive value for short-term adverse events.