The Diagnostic And Prognostic Values Of Pregnancy Associated Plasma Protein A (PAPPA) In Patients With Chronic Heart Failure

ObjectiveThe diagnosis of heart failure at home and abroad rely mainly on ultrasonic cardiogram and laboratory examination indexes B-type brain natriuretic peptide (BNP) or N-terminal pro-Brain Natriuretic Peptide (NT-proBNP). BNP is a indicator widely used for the diagnosis of heart failure, however, the diagnostic sensitivity and specificity of BNP is lower in patients with acute heart failure than those in heart failure patients with a reserved ejection fraction and at a progressive stage. It is generally known that the normal level of BNP is< 100 pg/mL. However, sometimes, we found some patients showed obvious signs and symptoms of heart failure without increased BNP levels. So we need to find a new biological marker to improve diagnostic accuracy. A laboratory biological indicator related to inflammation was reported abroad, pregnancy associated plasma protein A (PAPPA), which had a tendency to rise in patients with heart failure and closely linked with the patient prognosis. However, few studies have been implemented about the relationship between heart failure and PAPPA in China. This study suggests that PAPPA level has increased in patients with heart failure and demonstrated its value in diagnosis and prognosis of heart failure.Methods1. Experimental patients and groupsA total of 126 patients with heart failure were enrolled in the heart failure group(HF group),which was divided into 4 subgroups(Ⅰ,Ⅱ,Ⅲ and IV) according to the standard of American New York Heart Association (NYHA), and 40 healthy objectives were taken as controls. Mean age was 70±13 years old. Etiology include ischemic heart disease, dilated cardiomyopathy, hypertensive heart disease, valvular heart disease, hypertrophic cardiomyopathy, and chronic pulmonary heart disease.2. Measurement criteriaThe blood samples of all patients and controls were collected and all the following indexes, blood sugar, height, weight, TC, TG, LDL-C and HDL-C, were measured in the next morning. The resting blood pressure was taken twice every other day, and compute the average systolic blood pressure. BMI=weight (kg)/hight (m)2. Routine blood, liver, kidney, heart ultrasound, chest radiograph and other related inspection were preformed, the concentration of serum PAPPA and BNP were detected.3. MethodsSerum PAPPA and b-type brain natriuretic peptide (BNP) concentration was detected with double antibody sandwich method of enzyme linked immunosorbent assay (ELISA).4. StatisticsSPSS 17.0 software was used for statistical analysis. After statistical analysis, parameters with a normal distribution were expressed as mean and standard deviation (SD). Parameters that did not have a normal distribution were presented as median and inter-quartile range. The Kruskal-Wallis was compared between groups and the relationship between two factors was used Pearson correlation analysis. The selected patients were followed up for more than 1 year and survival data were analyzed by Kaplan-Meier method. A Cox proportional hazards regression analysis was performed to evaluate the associations between cardiac events and related factors. We portray the receiver operating characteristic (ROC) curve of PAPPA and BNP and use Youden’s index (sensitivity+accuracy-1) to determine the cutoff value.Results1.The concentration of PAPPA of the HF group were higher than that of the control group(P<0.05); which was the worse the cardiac function,the higher the PAPPA was.2.The ROC curve showed the cut-off value of PAPPA is 5.73ng/ml (sensitivity 79.44%, specificity 64.41%, AUC 0.755,95%CI 68% to 83%);3.The concentration of PAPPA in the HF group was positively correlated with BNP and left ventricular end-diastolic diameter (LVEDD) (r=0.399,0.432 respectively, P< 0.05),but negatively correlated with left ventricular ejection fraction (LVEF) (r=-0.402, P<0.05);4. Kaplan-Meier analysis demonstrated that the risk of cardiac events is higher in the high PAPPA group than those in the low PAPPA group.5.The Cox proportional hazards regression analysis showed that PAPPA is a independent risk factor for heart failure.Conclusion1. PAPPA concentration in patients with NYHA class I to class IV significantly was higher than that of patients in control group. The severity of heart failure in these patients was closely associated with the serum concentration of PAPPA That is to say, with the increase of PAPPA concentration, the cardiac functional grading of NYHA gradually increased.2. The correlation analysis showed that the serum levels of PAPPA were related to those of BNP in patients with heart failure (r=0.399, P<0.05), suggesting that serum levels of BNP and PAPPA could be used to evaluate the severity of cardiac function.3. The serum levels of PAPPA were positively correlated with LVEDD (r=0.432, P< 0.05) and the left ventricular ejection fraction (LVEF) (r=0.402, P< 0.05), reflecting the PAPPA is associated with the left heart structure and function. So we speculated that PAPPA might participate in the development of heart failure in the process of left ventricular remodeling.4. PAPPA may be used as a good indicator for the clinical diagnosis of heart failure and assessing the prognosis of patients with cardiac failure.