Clinical Studies On SST2 And Cystatin C In The Diagnosis And Prognosis Of Heart Failure Patients With Preserved Ejection Fraction

Part I. Comparative analysis the clinical features in patients with heart failure with preserved and reduced ejection fractionObjective:To analysis the clinical behavior in patients with heart failure with preserved and reduced ejection fraction.Methods:From May 2014 to January 2015,288 hospitalized heart failure patients were selected in Department of Cardiology, Chizhou People's Hospital in Anhui province. 182 cases were male, and 106 cases were female. There were 120 patients with heart failure with preserved ejection fraction (HF-PEF). Others were patients with heart failure with reduced ejection fraction (HF-REF). Patient's information with gender, age, hypertension, coronary heart disease, atrial fibrillation, cardiac function, hemoglobin, serum creatinine, blood uric acid, triglyceride, total cholesterol, low density lipoprotein, high density lipoprotein, NT-proBNP and estimated glomerular filtration rate (eGFR) value was collected. Classification of cardiac function was according to NYHA classification. eGFR was calculated to use the modified simplified MDRD equation for Chinese people. eGFR (ml/min/1.73m2)= 186* serum creatinine (mg/dL)-1.154* age-0.203* 1.233* 0.742 (female). Echocardiography data of patients was recorded. These data was left atrial diameter, left ventricular diameter, interventricular septum thickness, left ventricular posterior wall thickness, left ventricular ejection fraction, E peak, A peak and E peak/A peak. Biochemical and echocardiographic parameters between HF-PEF and HF-REF patients were compared. Heart function classification of HF-PEF with HF-REF was compared.Results:(1) HF-PEF patients were 120 cases in this group of 288 heart failure patients. They were accounting for 41.67%. The age of patients in HF-PEF group was 65.61+9.74 years old, while the age of HF-REF group was 62.53+11.51 years old. There was a significant difference between the two groups (P<0.05). Women patients were 55 cases (45.83%) in HF-PEF group, and women patients were 51 cases (30.36%) in HF-REF group. Compared to the two groups, the relative majority of women in HF-PEF group, the difference is statistically significant (P<0.05). The incidence of hypertension in patients with HF-PEF was greater than HF-REF group (P<0.05). The incidence of CHD in patients with HF-PEF was greater than HF-REF group (P<0.05). The incidence of atrial fibrillation in patients with HF-PEF was greater than HF-REF group (P<0.05). (2) Compared with HF-REF group, the values of hemoglobin, serum creatinine, serum uric acid and LgNT-proBNP in HF-PEF group were lower. The difference was statistically significant (P<0.05). The value of eGFR in HF-PEF group was higher than that in HF-REF group (P<0.05). (3) Compared with HF-PEF patients, the value of left atrial diameter, left ventricular diastolic end diastolic diameter, E peak and E peak/A peak was greater in HF-REF patients (P<0.05). Compared with HF-REF patients, the value of interventricular septum thickness, left ventricular posterior wall thickness, EF value and A peak was greater in HF-PEF patients (P<0.05). The differences were statistically significant. (4) According to NYHA cardiac function classification, cardiac function ? grade was 28 cases (23.33%) in HF-PEF group; cardiac function ? grade was 74 cases (61.67%), and cardiac function ? grade 18 cases (15%). Cardiac function ? grade was 33 cases (19.64%) in HF-REF group; cardiac function ? grade was 105 cases (62.50%), and cardiac function ? grade 30 cases (17.86%). There was no significant difference in NYHA cardiac function classification between the two groups (P>0.05).Conclusions:(1) The incidence of HF-PEF patients was high in all heart failure patients. (2) Compared with HF-REF group, female was much more in HF-PEF group. The patients in HF-PEF group were much older. The incidence rate of hypertension, CHD and atrial fibrillation in HF-PEF group was higher than that of HF-REF group. (3) NT-proBNP value of HF-PEF group was lower than that of HF-REF group. The assesment value of NT-proBNP was greater for HF-REF patients. (4) Echocardiography was widely used in the evaluation of patients with HF-PEF and HF-REF. It was still the most important diagnostic tool for HF-PEF patients.Part II. The diagnostic value of sST2 and cystatin C in patients with heart failure with preserved ejection fractionObjective:To evaluate the diagnostic value of serum sST2 and cystatin C in patients with heart failure with preserved ejection fraction.Methods:From May 2014 to January 2015,120 patients with heart failure with preserved ejection fraction (HF-PEF) were selected in Department of Cardiology, Chizhou People's Hospital in Anhui province.65 cases were male (54.17%), and 55 cases were female (45.83%). Age was 65.61±9.74 years old. There were 82 cases in healthy control group. They were healthy population in the same period in Anhui province Chizhou People's Hospital.45 cases were male (54.88%), and 37 cases were female (45.12%). Age was 64.79+9.68 years old. Gender and age of baseline data in the two groups was not statistically significant. The serum level of sST2, C cystatin and NT-proBNP was measured in two groups. Their information with gender, age, left ventricular ejection fraction, cardiac function, serum sST2, NT-proBNP and serum C cystatin values were collected. Classification of cardiac function was according to NYHA classification. sST2, cystatin C and NT-proBNP values between HF-PEF group and healthy control group were compared. Serum sST2 and cystatin C levels in HF-PEF group with different heart function classification were compared. Bivariate correlation analysis for the relationship between sST2, cystatin C and LVEF, LgNT-proBNP. Pearson linear correlation analysis was used in these indicators. The application of AUC in the ROC curve of sST2, cystatin C and joint detection with NT-proBNP was in the diagnosis of HF-PEF.Results:(1) The levels of sST2, cystatin C and LgNT-proBNP in HF-PEF group were significantly higher than those in healthy control group, the difference was statistically significant (P<0.05). (2) Serum sST2 levels in patients with NYHA class IV was apparently greater than that in patients with cardiac function grade ? and cardiac function grade II. Serum sST2 levels in patients with NYHA class ? was apparently greater than that in patients with NYHA class ?. There were statistically significant differences in the three groups (P<0.05). The cystatin C level gradually increased with heart function level increasing. The differences were statistically in the three groups (P<0.01). (3) Pearson linear correlation analysis showed that there was no correlation between serum sST2 and LVEF. Serum C cystatin was negatively correlated with LVEF (r=-0.162, P<.05). The value of serum sST2 was positively correlated with the value of NT-proBNP (r=0.771, P<O.05). The value of serum C cystatin was positively correlated with the value of NT-proBNP (r=0.220, P<0.05). (4) The ROC curves of sST2, cystatin C and NT-proBNP to diagnosis HF-PEF were produced. The AUC of serum sST2 to diagnose HF-PEF was 0.635 (95% CI: 0.534-0.735), the optimal diagnostic cut-off value was 49.63pg/ml, sensitivity was 53.75%, specificity was 83.33%. The AUC of serum cystatin C to diagnose HF-PEF was 0.841 (95% CI:0.761-0.922), the optimal diagnostic cut-off value was 0.99 mg/L, sensitivity was 80.00%, specificity was 77.78%%. The AUC of serum NT-proBNP to diagnose HF-PEF was 0.849 (95% CI:0.774-0.924), the optimal diagnostic cut-off value was 512.95pg/ml, sensitivity was 71.25%, specif icity was 75.00%. (5) The ROC curves of sST2+NT-proBNP, cystatin C+NT-proBNP and NT-proBNP to diagnosis HF-PEF were produced. The AUC of serum sST2+NT-proBNP to diagnose HF-PEF was 0.868 (95% CI:0.801-0.934). The AUC of serum cystatin C+NT-proBNP to diagnose HF-PEF was 0.911 (95% CI:0.857-0.966).Conclusions:(1) The serum levels of sST2 and cystatin C in HF-PEF patients were usually higher than those in healthy people. (2) The levels of serum sST2 and cystatin C in patients with HF-PEF were remarkably correlated with the severity of heart failure. The levels of serum sST2 and cystatin C were the predictive factors for the degree of cardiac insufficiency. (3) Serum sST2 and cystatin C were the new biomarkers for the diagnosis of HF-PEF. The combined application of sST2, cystatin C and NT-proBNP could improve the value to diagnosis HF-PEF much more than the use of NT-proBNP alone. Serum sST2 and cystatin C could be a supplementary means of NT-proBNP, and improved the diagnostic value of HF-PEF.Part III. Prognostic prediction value of sST2 and cystatin C in patients with heart failure with preserved ejection fractionObjective:To estimate the forecast value of serum sST2 and cystatin C in predicting the prognosis of patients with heart failure with preserved ejection fraction.Methods:From June 2014 to August 2015,220 patients with heart failure with preserved ejection fraction were selected in Department of Cardiology, Chizhou People's Hospital in Anhui province.132 cases were male, and 88 cases were female. Age was 68.35±10.82 years old. The serum levels of sST2, cystatin C and NT-proBNP were measured in HF-PEF patients. Patient's information with gender, age, left ventricular ejection fraction, serum sST2, NT-proBNP and serum C cystatin values were collected. According to the level of serum sST2, HF-PEF patients were divided into two groups, namely the sST2 low level group:serum sST2 was equal to or less than 50 pg/ml, sST2 high level group:serum sST2>50 pg/ml. According to the serum cystatin C level, HF-PEF patients were divided into two groups, namely cystatin C normal group:Serum Cystatin C was equal to or less than 1.15 mg/L and cystatin C increased group:Serum Cystatin C>1.15 mg/L. The selected cases were given standardized treatment after hospitalization and discharge. The death of cases after discharged from hospital and the situation of rehospitalization for cardiac causes was followed up. The duration of follow-up was at least 6 months (180 days), and the terminal point of follow-up was known to occur during the period. Follow up by telephone follow-up and outpatient combination. The value of serum sST2, cystatin C and joint detection with NT-proBNP in the prognosis of patients with HF-PEF was analyzed by using ROC curve. The survival curve was drawn by Kaplan-Meier method. Survival analysis used Log-rank test.Results:(1) All HF-PEF patients were followed up for 180 to 420 days, and the median follow-up time was 270 days. A total of 17 patients died during the follow-up period, and the incidence was 7.73%. There were 78 patients who were hospitalized due to cardiac causes, and the incidence was 35.45%. (2) The ROC curves of sST2, cystatin C and NT-proBNP were used to predict all-cause death in HF-PEF patients. The AUC of serum sST2 to predict all-cause death in HF-PEF patients was 0.704 (95% CI:0.563-0.846), the optimal diagnostic cut-off value was 63.02 pg/ml, sensitivity was 58.82%, specificity was 81.77%. The AUC of serum cystatin C to predict all-cause death in HF-PEF patients was 0.774 (95% CI:0.667-0.882), the optimal diagnostic cut-off value was 1.20 mg/L, sensitivity was 70.59%, specificity was 78.33%. The AUC of serum NT-proBNP to predict all-cause death in HF-PEF patients was 0.428 (95% CI:0.259-0.596). (3) The ROC curves of sST2, cystatin C and NT-proBNP were used to predict all-cause death or cardiac rehospitalization in HF-PEF patients. The AUC of serum sST2 to predict all-cause death or cardiac rehospitalization in HF-PEF patients was 0.596 (95% CI:0.514-0.678), the optimal diagnostic cut-off value was 75.85 pg/ml, sensitivity was 26.92%, specificity was 95.77%. The AUC of serum cystatin C to predict all-cause death or cardiac rehospitalization in HF-PEF patients was 0.605 (95% CI:from 0.524-0.686), the optimal diagnostic cut-off value was 1.34 mg/L, sensitivity was 33.33%, specificity was 90.14%. The AUC of serum NT-proBNP to predict all-cause death or cardiac rehospitalization inHF-PEF patients was 0.517 (95% CI:0.438-0.595). (4) The ROC curves of sST2+NT-proBNP, cystatin C+NT-proBNP and NT-proBNP were used to predict all-cause death or cardiac rehospitalization in HF-PEF patients. The AUC of serum sST2+NT-proBNP to predict all-cause death in HF-PEF patients was 0.708 (95% CI:0.567-0.850). The AUC of serum cystatin C+NT-proBNP to predict all-cause death in HF-PEF patients was 0.791 (95% CI:0.683-0.900). The AUC of serum sST2+NT-proBNP to predict all-cause death or cardiac rehospitalization in HF-PEF patients was 0.616 (95% CI:0.534-0.698). The AUC of serum cystatin C+NT-proBNP to predict all-cause death or cardiac rehospitalization in HF-PEF patients was 0.611 (95% CI:0.530-0.691). (5) The incidence of death and cardiac rehospitalization in sST2 high level group HF-PEF patients were greater than that in sST2 low level group (P< 0.05). The incidence of death and cardiac rehospitalization in Cystatin C increased group HF-PEF patients were greater than that in Cystatin C normal group (P< 0.05). (6) The Kaplan-Meier method was used to analyze survival curve of HF-PEF patients with sST2 low level group and sST2 high level group during follow-up period. The results showed that the all-cause mortality of sST2 high level group was apparently greater than that of sST2 low level group during the follow-up period, the statistical value of Log-rank test was 5.49, P< 0.05. The all-cause mortality or cardiac rehospitalization rate of sST2 high level group was apparently greater than that of sST2 low level group during the follow-up period, the statistical value of Log-rank test was 6.76, P< 0.01. (7) The Kaplan-Meier method was used to analyze survival curve of HF-PEF patients with cystatin C normal group and cystatin C increased group during follow-up period. The results showed that the all-cause mortality of cystatin C increased group was apparently greater than that of cystatin C normal group during the follow-up period, the statistical value of Log-rank test was 14.54, P< 0.01. The all-cause mortality or cardiac rehospitalization rate of cystatin C increased group were significantly higher than that of cystatin C normal group during the follow-up period, the statistical value of Log-rank test was 8.30, P< 0.01.Conclusions:(1) There were adverse prognostic predicted values of high level of serum sST2 in HF-PEF patients. The evaluation of prognostic value in patients with HF-PEF had significant role by monitoring the changes of serum sST2 level. (2) Serum cystatin C had an important guiding significance on the prognosis of patients with HF-PEF. In clinical practice, the detection of serum cystatin C level is expected to have application value to evaluate the prognosis. (3) Serum sST2 and cystatin C has potential research value of biomarkers in patients with HF-PEF. Serum sST2 and cystatin C had a strong guiding significance to predict mortality and cardiac readmission rate in patients with HF-PEF. The role of serum sST2 and cystatin C in the evaluation of the prognosis of patients with HF-PEF had even more than that of traditional markers NT proBNP. (4) The combined application of serum sST2 and cystatin C could greatly improve the evaluation ability of prognosis in HF-PEF patients. Serum sST2 and cystatin C could be used as a powerful supplement with NT-proBNP to the prognosis of HF-PEF patients.