Role Of Cystatin C And N-Terminal Pro-BNP In Hospitalized Copd Patients With Preserved Left Ventricular Ejection Fraction

Objectives:To identify the role of NTproBNP and cystatin c in patient of COPD with preserved ejection fraction.To determine the role of NTproBNP and Cystatin c in both Stable COPD and acute exacerbated COPDTo determine effect of NTproBNP and Cystatin with regard toduration of hospitalization in both and AECOPD and SCOPDMethodology:Its hospital based retrospective cross section study review admitted patient with diagnosis of COPD at Qilu hospital of Shandong University.Analyzed data were of admitted patients at Qilu hospital in the respiratory department diagnosed with COPD from January 2013 to November 2017.COPD defined as ratio of force expiratory volume in one second/force vital capacity(FEV1/FVC)less than 70%after bronchodilator test based on ICD 10 criteria/American thoracic society criteria.Furthermore,COPD was categorized in two major groups'acute exacerbation COPD(AECOPD)and stable COPD(SCOPD).Defined AECOPD as new onset or worsening respiratory symptoms(wheezing,difficult breathing,sputum purulent,fever)which require addition of new drug/s as per GOLD definition,whereas defined stable COPD as patient with known COPD but with no new symptoms that require new addition of drug/s.Baseline data obtained included demographic data,age,sex,weight and BMI was calculated.Data of the serum biomarkers Cystatin c,N-terminal pro BNP were retrieved from hospital data pool,other parameters included echocardiographic results of left ventricular ejection fraction.Normal ejection fraction(EF)defined as preserved ejection fraction when EF is equal or above 50%,and cut off value set for concentration level of NT-proBNP and cystatin c of>900pg/mL and 0.9mg/L respectively.Other blood tests included serum creatinine,cholesterol,Low density lipoprotein(LDL),triglyceride,white blood cell counts and high density lipoprotein(HDL).NT-proBNP was log-transformed to reduce extreme values.Ethical clearance was requested and approved by the institution research administrative committee.Sample size;Initial sample size was 4038 patients followed exclusion and inclusion criteria analyzed data of 1999 COPD patients.Inclusion criteria were patient aged above 18 years,diagnosed with COPD based on ATS criteria.Patients with other diagnoses includes renal failure,malignancy,interstitial lung diseases,asthma with no COPD,recently stroke and myocardial infarction where excluded from our study.Data were analyzed using SPSS version 16.Kolmogorov-smirnov method was used to ensure data normality.Data that were normally distributed were expressed in as mean ± standard deviation(SD)and median(range)was used for non-normal distributed data.Mann-Whitney test or Independent sample t test was used to compare difference between two groups,chi square was used for frequency data test.Correlations between cystatin c,log-transformed NTproBNP and left ventricular ejection fraction,hospital admission(days),age,and other laboratory blood results were analyzed using the spearman correlation test and liner regression model also was used to find relationship between dependent variables(log-transformed NTproBNP,cystatin c).p value statistical significant if?0.05.Results;A total of 1999 patients with Chronic obstructive lung diseases were studied,1387(69.2%)were male and 612(30.6%)were female,giving male to female ratio of 2.3/1.Patients with acute exacerbation COPD(AECOPD)were 1637 cases(81.7%)and stable COPD(SCOPD)were 362(18.1%).The mean weight of 52±24.7 and mean age of the study was 72.60±10.196.This study found,based on seasonal admission,winter season has high incidence of admission of COPD patients(33.6%),followed by summer(28.0%),and there was no admission difference between autumn and spring,whereby in autumn incidence of admission was(19.7%),spring has lowest admission incidence(18.5%).The mean days of hospital stay was 12±6 days,with minimum duration of hospital admission of 1 day and maximum duration spent by admitted patient was 64 days.From retrieved data,left ventricular ejection fraction results of 886 COPD patients was obtained,whereby 795 patients(89.7%)had preserved ejection fraction and 91(10.3%)patients had reduced left ventricular ejection fraction.Cystatin c and COPD in relation to NT-pro BNPIn this study,results found that cystatin c level increases significantly with the increased NTproBNP,correlation coefficient r=0.042,p<0.001,C.I 95%,however there was no difference between cystatin c in AECOPD and SCOPD(1.206±0.47,1.180±0.47)P=0.45,The level of NTproBNP was significant higher in AECOPD(mean 1420±3419pg/mL)than SCOPD(1015±2514pg/mL)(p<0.039).Based on sex preference,there was no sex difference between AECOPD and SCOPD(p<0.76),moreover,correlationship between creatinine and cystatin c found positively correlated 0.320(p<0.001).Hospital admission wasfound prolonged in COPD patients with higher level of Cystatin c p<0.003,and elevated log-transformed NTproBNP level p<0.001.The mean LV ejection fraction of AECOPD and SCOPD were(60.28±11.09%),(60.19±9.24%)respectively.Serum biomarker cystatin c showed weak negative correlation with LV ejection fraction-0.068(p<0.044),however there is moderate negative correlation coefficient between log-transformed NTproBNP with LV ejection fraction-0.303(p<0.001).Cystatin c level and NTproBNP were significantly positive correlated with age(correlation coefficient r=0.262 p<0.001),(correlation coefficient r=0.252),p<0.001 respectively.Furthermore,we found that elevated neutrophils and white blood cell correlate with exacerbation COPD(p-value<0.001,p<0.001 respectively).ConclusionSerum Cystatin c and NTproBNP found to be independent usefully biomarker that may be used to determine progression and involvement of COPD with left ventricular functional changes that includes its progressionand for follow-up management,in this study results found that early changes occurred in COPD patients involving left ventricles may be associated with heightened level of NTproBNP and cystatin c.Furthermore,elevated level of cystatin c and NTproBNP was associated with prolongation of duration of hospitalization of COPD with left ventricular EF and triggers its exacerbation rate.However,Cystatin c may be used as reliable markers for determining progression and outcome of AECOPD and SCOPD but with limitation since it may not be used to differentiate the two.Further prospective studies with large sample size is needed to be done to determine role of cystatin c in COPD based on right ventricular involvement and severity of COPD including lung function test as per GOLD definition.