Study Of Red Blood Cell Distribution Width As A Prognostic Marker In Heart Failure Patients

Heart failure (HF) is the terminal stage of heart disease caused by various reasons. Many clinical diseases such as coronary heart disease, hypertension and pulmonary emphysema can lead to pathological changes of the heart. When diseases progress in the end-stage, they would turn out symptoms of heart failure. Along with the number of aged people increasing, incidences of coronary heart disease and hypertension, which is common and frequently-occurring in old people, increase year after year. In addition, as the medical technology developping, diagnosis and treatment improving, there are marked inceases in survival rates of heart disease patient, which leads to the increasing significantly in the patients of the world. Heart failure is a chronic and continuous developing process with poor short and long-term prognosis, and with high mortality. It is reported that mortality of patients with chronic heart failure can reach60%in five years;1-year mortality of patients with worse illness can achieve50%. Once suffering from heart failure, patients have to repeatedly hospitalize due to recurrence of heart failure symptoms. The heavy economic and psychological burdens on patients themselves and their families decrease patients’life quality. Some patients can even not take care of themselves. Heart failure becomes a serious disease that impacts on public health around the world, so it is necessary to find effective prognostic indicators that can accurately stratify patients with poor prognosis in the early development of the disease, and then clinicians can execute positive and effective intervention treatments to improve patient outcomes.The changes in the shape and size of red blood cells in the peripheral blood are often associated with the occurrence and development of blood system diseases. However, researchers have found that it has a certain relationship with the prognosis of cardiovascular diseases recently. Red blood cell distribution width (RDW), an index reflecting the red blood cell size changes in peripheral blood, may have a certain value in predicting short and long-term prognosis in patients with heart failure.ObjectiveThe purpose of this thesis is to confirm the relationship between RDW and long-term prognosis of heart failure, and to analyze the predictive value of RDW on two-year mortality risk by a retrospective analysis of patients admitted to hospital for heart failure. Then in order to explain the mechanism of RDW predicting the prognosis, the differences of predictive value of RDW in different causes of heart failure are compared. At last, the reasons why RDW increased in heart failure patients are discussed.Materials and Methods1Object1021consecutive patients with heart failure hospitalized in heart failure ward from October2009to December2011. Excluding the following patients:with incomplete medical records, under18years old, with diseases such as anemia, leukemia, malignant tumor, serious liver or kidney disease, digestive tract hemorrhage, and other diseases that could possibly change RDW. The patients with infectious endocardium inflammation, aortic dissection, constriction pericarditis, hydropericardium and pulmonary thromboembolism were also excluded. Selected patients were aged from18to90years old, with720males and301females. 2Methods2.1Collect patients’clinical information on admissionAccording to the medical records of patients, information of age, gender, BMI and complication diseases, such as hypertension, hyperlipidemia and diabetes, were collected on admission. NYHA heart function classification, ultrasonic cardiogram results on admission, as well as the earlist routine blood test and biochemical test results after admission was recorded.2.2Collect patients’blood samplesFasting blood were collected from patients by highly trained nurses the next morning after admission. Specimen was timely sent to the Clinical Laboratory Center after collection and executed routine blood, biochemical, amino-terminal B-type natriuretic peptide (NT-proBNP) and other tests as soon as possible. Routine blood and NT-proBNP tests were collected in EDTA anticoagulant tubes, and biochemical tests in tubes without anticoagulant2.3Testing equipmentRDW, Red blood cell count (RBC), Hemoglobin (Hb) were tested by Sysmex XE-2100blood cell analyzers and mating reagents; Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Total Bilirubin (TBil), blood urea nitrogen (BUN), serum creatinine (Cr); high-sensitivity C-reactive protein (hs-CRP) by Olmplus AU5100biochemistry analyzer and the reagents produced by Biosino bio-technology and science incorporation; NT-proBNP with enzyme-linked immunosorbent kit produced by Biomedica company and ELx800microplate reader producted by Bio-Tek; left ventricular ejection fraction (LVEF) with Philips iE33all-digital echocardiography.2.4Follow-upPrognosis of patients was followed-up:as for patients who died in hospital, time of death and causes of death were recorded; for patients discharged, time of discharge and the last RDW test results before discharge were recorded; patient himself or his family was followed-up by telephone, situation of re-hospitalization or death were recorded after discharge. Readmission is that patients hospitalized with heart failure or symptoms appear again (including inpatients and emergency hospitalization). Death is all causes of death after discharge.3Statistics analysisThe data was analyzed statistically by SPSS17.0version.RDW was non-normal distribution data and representated as median [first quartile, third quartile, M (Q1, Q3)]. Two group compared by t test or Mann-Whitney U test or Kruskal Walks’H test, further comparisons by Bonferroni. The survival rate of patients estimated by Kaplan-Meier and log-rank tested the difference between two groups. ROC curve analysed the predictive value of RDW for death risk in heart failure patients, areas under the curve were compared by Z test. Cox proportional hazards models assessed the independent predictors of death risk in patients with heart failure. Spearman analysed the correlation between RDW and other indicators. The RDW impact factors were analysed by multiple linear stepwise regression. P<0.05means statistically significance.Results1General information of selected patients:1021cases meeting the admission criteria, the median RDW in these patients was13.5%, RDW≥15%patients account for17%. After follow-up a median693days,116cases lost, loss rate was11.4%.137cases died during follow-up, mortality rate was15.1%, RDW in patients of death was14.8%, signifficantly higher than that(13.3%) of survivors(P<0.001). Death patients have lower BMI and blood pressure, faster heart rate, poorer heart function, higher RDW and more patients with liver and kidney abnormal.2Increased RDW related to the increased two-year risk of death and rehospitalization:The mortality rate of patients with abnormal RDW (≥15.0%) was34.8%, readmission rate was31.6%, mortality rate of normal patients was11.0%, re-hospitalization rate was33.6%. The mortality rate of patients with abnormal RDW was significantly higher than that of patients with normal RDW, and the survival time was shorter. Cox regression analysis showed that RDW was related to two-year prognosis in heart failure patients and the risk of death with abnormal RDW was about4times higher than that of normal patients(adjusted HR=3.77).3RDW had a certain predictive value for two-year prognosis in patients with heart failure:ROC curve analysis, area under the curve (AUC) was0.716(P<0.001). When Youden index reached the maximum, cutoff value of RDW was13.45%, the predicted sensitivity76.3%, specificity56.7%, positive predictive value24.2%and negative predictive value93.7%.4RDW, mortality and survival time in patients with different causes of heart failure were different:Coronary heart disease, dilated cardiomyopathy and valvular heart disease patients, three major causes of heart failure, were selected as investigated subject. RDW, mortality and survival time were significantly different in three groups. RDW and mortality in valvular heart disease and dilated cardiomyopathy patients were significantly higher than that of coronary heart disease, survival time was shorter, while there was no difference between patients of valvular heart disease and dilated cardiomyopathy.5The predictive value of RDW for the two-year risk of death in different causes of heart failure patients was different:ROC curve analysis showed that RDW had predictive value for death in heart failure caused by coronary heart disease and dilated cardiomyopathy, AUC was0.704,0.753, respectively (allP<0.001); no value in valvular heart disease, AUC was0.593(P=0.168). When Youden index reached the maximum, the sensitivity of RDW in coronary heart disease was59%, specificity75%, the sensitivity in dilated cardiomyopathy was60%and a specificity of79%.6The related risk factors of elevated RDW:As RDW elevated, the patient’s BMI and LVEF decreased and heart function become worse. The correlation coefficients of RDW with BMI, LVEF and cardiac function classification were0.230,-0.261,0.357, respectively (allP<0.001). RDW related to Hb, TBil, hs-CRP and NT-proBNP, correlation coefficients were-0.092,0.363,0.205,0.442, respectively (all P<0.01). Multiple linear stepwise regression analysis showed that increased RDW was affected by BMI decline, NYHA functional classification rise, NT-proBNP, TBil and hs-CRP increase, but the biggest impact on RDW was bilirubin metabolism abnormity. Conclusions1. RDW can be used as a prognostic indicator in patients with congestive heart failure, forecasts sensitivity for the two-year mortality risk is similar to NT-proBNP.2. In patients with different etiology, predicting values of RDW are different. RDW can be used as prognostic indicators of heart failure caused by coronary heart disease and dilated cardiomyopathy, but have no predictive value on valvular heart disease, which may provide the basis for RDW in specific clinical application.3. Higher RDW in patients with heart failure under the influence of many factors, elevated total bilirubin is an important factor. Causes of RDW elevated in patients with congestive heart failure with poor prognosis, follow-up studies are needed to explain.