what is less appreciated is that , according to the us renal data system , 217 hospitalisations per 1,000 patient - years are attributed to congestive heart failure ( chf ) . in the general population , single measurements of brain natriuretic peptide ( bnp ) and its n - terminal fragment ( nt - probnp ) accurately discriminate between chf and other causes of breathlessness that lead to hospital admissions .
concentrations of these natriuretic peptides are related to left ventricular ( lv ) filling pressures and wall stress . in dialysis patients , fluid overload and lv structural and functional abnormalities are both frequent and difficult to differentiate . in dialysis patients , bnp and nt - probnp levels
single , cross - sectional measurements of nt - probnp are powerful predictors for all - cause mortality and cardiovascular death , and baseline nt - probnp measurements may facilitate efforts to stratify the risk in patients starting hd .
however , few studies have examined the diagnostic utility of serial assessments of nt - probnp in the hd population .
nevertheless , monitoring bnp levels is currently used for patients with heart failure as troughton et al
.   showed that bnp - guided treatment of heart failure reduced total cardiovascular events and delayed the time to the first event compared with intensive clinically guided treatment . in the family of natriuretic peptides
, nt - probnp seems to be the best predictor of clinical outcome and the best marker of extracellular fluid overload .
this peptide is larger and has a longer half - life than bnp ( the active form ) , making its measurement easier .
therefore , we sought to examine the relationship between an increase in nt - probnp levels and future clinical events in a prospective cohort , i.e. whether follow - up nt - probnp measurements add further prognostic information in hd patients .
more specifically , we assessed the value of the relative changes in nt - probnp as independent predictive markers of chf events .
a prospective cohort study of hd patients was conducted during 18 months . both prevalent and
the medical history of all patients was collected at baseline , and events occurring during follow - up were systematically recorded .
patients were followed up for the occurrence of medical adverse events , i.e. chf events , cardiac ischaemia , arrhythmia , hospitalisation for other cardiac events or infectious disease , and death .
the patients were censored at the time of renal transplantation , death , and first chf event .
this study was approved by the local institutional review board , and informed consent was obtained from all patients who participated in the study . at the beginning of the follow - up , i.e. at baseline , measurement of the nt - probnp level was performed every month .
serum nt - probnp was quantified by electrochemiluminescence immunoassay on the cobas e601 analyser ( roche diagnostics corp . ) .
the variability of the nt - probnp assay is always below 6% in our lab ( recommended : below 9% ) .
a chf event was defined as the first admission for chf requiring hospitalisation and any episode of chf requiring a session of additional dialysis as an emergency in our centre .
the clinical diagnosis of chf was made by the attending physician on the basis of the presence of symptoms and signs of chf including moderate to severe dyspnoea ( class iii and iv according to the new york heart association ) , raised jugular venous pressure , and basal crepitations .
this information was retrieved from the computerized medial medical record system ( echo , nantes , france ) that keeps detailed records of all hospitalisation and/or acute events .
the following characteristics of the patients were collected at baseline to adjust our analyses : age and sex , weight and height ( body mass index ) , time on dialysis , comorbidities including diabetes , coronary artery disease , valvular heart disease , arrhythmia , hypertrophic cardiomyopathy , dilated cardiomyopathy , and altered lv ejection fraction ( lvef ; < 40% on 2-dimensional echocardiography ) .
quantitative variables were presented as mean  standard deviation ( min  max ) and binary variables were presented as proportions .
then , patients were divided according to the outcome criteria , i.e. the occurrence of a chf event , and their characteristics and levels of nt - probnp at baseline were compared .
we assessed the evolution of nt - probnp separately in patients without a chf event and in patients who developed a chf event .
this regression analysis was a nested case - control study . in a nested case - control study ,
cases of a disease that occur in a defined cohort are identified and , for each , a specified number of matched controls is selected from among those in the cohort who have not developed the disease by the time of disease occurrence in the case .
the nested case - control design is particularly advantageous for studies of biologic disease precursors .
the evolution of the nt - probnp measurements before a chf event was compared to the evolution of the nt - probnp measurements at the same time for the controls , using a polynomial regression for repeated measurements .
then , the usefulness of the relative change in nt - probnp level to predict the risk of a chf event was assessed by the analysis of receiver operating characteristic ( roc ) curves . the relative change in nt - probnp was defined as the proportion of increase or decrease in nt - probnp measured compared to the previous measurement .
a prospective cohort study of hd patients was conducted during 18 months . both prevalent and
the medical history of all patients was collected at baseline , and events occurring during follow - up were systematically recorded .
patients were followed up for the occurrence of medical adverse events , i.e. chf events , cardiac ischaemia , arrhythmia , hospitalisation for other cardiac events or infectious disease , and death .
the patients were censored at the time of renal transplantation , death , and first chf event .
this study was approved by the local institutional review board , and informed consent was obtained from all patients who participated in the study .
at the beginning of the follow - up , i.e. at baseline , measurement of the nt - probnp level was performed every month .
serum nt - probnp was quantified by electrochemiluminescence immunoassay on the cobas e601 analyser ( roche diagnostics corp . ) .
the variability of the nt - probnp assay is always below 6% in our lab ( recommended : below 9% ) .
a chf event was defined as the first admission for chf requiring hospitalisation and any episode of chf requiring a session of additional dialysis as an emergency in our centre .
the clinical diagnosis of chf was made by the attending physician on the basis of the presence of symptoms and signs of chf including moderate to severe dyspnoea ( class iii and iv according to the new york heart association ) , raised jugular venous pressure , and basal crepitations .
this information was retrieved from the computerized medial medical record system ( echo , nantes , france ) that keeps detailed records of all hospitalisation and/or acute events .
a chf event was defined as the first admission for chf requiring hospitalisation and any episode of chf requiring a session of additional dialysis as an emergency in our centre .
the clinical diagnosis of chf was made by the attending physician on the basis of the presence of symptoms and signs of chf including moderate to severe dyspnoea ( class iii and iv according to the new york heart association ) , raised jugular venous pressure , and basal crepitations .
this information was retrieved from the computerized medial medical record system ( echo , nantes , france ) that keeps detailed records of all hospitalisation and/or acute events .
the following characteristics of the patients were collected at baseline to adjust our analyses : age and sex , weight and height ( body mass index ) , time on dialysis , comorbidities including diabetes , coronary artery disease , valvular heart disease , arrhythmia , hypertrophic cardiomyopathy , dilated cardiomyopathy , and altered lv ejection fraction ( lvef ; < 40% on 2-dimensional echocardiography ) .
quantitative variables were presented as mean  standard deviation ( min  max ) and binary variables were presented as proportions .
then , patients were divided according to the outcome criteria , i.e. the occurrence of a chf event , and their characteristics and levels of nt - probnp at baseline were compared .
we assessed the evolution of nt - probnp separately in patients without a chf event and in patients who developed a chf event .
this regression analysis was a nested case - control study . in a nested case - control study ,
cases of a disease that occur in a defined cohort are identified and , for each , a specified number of matched controls is selected from among those in the cohort who have not developed the disease by the time of disease occurrence in the case .
the nested case - control design is particularly advantageous for studies of biologic disease precursors .
the evolution of the nt - probnp measurements before a chf event was compared to the evolution of the nt - probnp measurements at the same time for the controls , using a polynomial regression for repeated measurements .
then , the usefulness of the relative change in nt - probnp level to predict the risk of a chf event was assessed by the analysis of receiver operating characteristic ( roc ) curves . the relative change in nt - probnp was defined as the proportion of increase or decrease in nt - probnp measured compared to the previous measurement .
the mean age of the population was 59.84  17.4 years ( 18.388.3 ) , and 36% were female .
the mean hd duration was 46  74.3 months ( 0482 ) . in total , 61.4% of our patients were caucasian , 11.5% were black , and 27.1% of other origins .
patients had a history of diabetes in 25% of the cases and a history of coronary artery disease in 30.5% .
echocardiographic data from baseline showed hypertrophic cardiomyopathy , dilated cardiomyopathy , and altered lvef in 25.4 , 7.2 , and 23% of the cases , respectively .
the mean follow - up was 12.5 months ( 218 ) , during which 44 ( 18.6% ) patients developed a chf event , of which 22 patients required hospitalisation and 22 patients required a session of additional dialysis in our centre .
the length of hospitalisation was 8.64  6.1 days ( 121 ) , depending on the need for further exploration or the patient 's general condition .
table 1 provides a comparison of the patients baseline characteristics according to their evolution with or without a chf event .
baseline nt - probnp levels were significantly higher among patients who subsequently developed a chf event than among those who did not ( 2,438 vs. 7,982
patients who developed a chf event had significantly more dilated cardiomyopathy ( 18.2 vs. 4.7% , respectively ) and/or altered lvef ( 47.7 vs. 17.2% , respectively ) at baseline compared with patients who did not develop a chf event .
the body mass index was lower in the group of patients who subsequently developed a chf event .
the graphical representation of the evolution of nt - probnp before a chf event showed a clear increase of the biomarker during the months preceding the chf event ( fig .
the regression analysis showed that this difference of evolution was statistically significant ( p < 0.05 ) for the measurement during approximately the 2 months preceding the event .
the proportion of the increase or decrease in nt - probnp measured at two consecutive visits was assessed as a predictor of a chf event ( fig .
the auc was 0.80 . if the threshold of positivity was chosen in favour of specificity , then , at 20% of the relative increase in nt - probnp , the sensitivity of the test was 0.57 and the specificity 0.77 . if the threshold was chosen in favour of sensitivity , then , if all positive relative changes were considered as predictors , the sensitivity was 0.97 but at the price of a low specificity of 0.59 .
only 1 patient had a decrease in nt - probnp between the two last visits before a chf event .
the mean age of the population was 59.84  17.4 years ( 18.388.3 ) , and 36% were female .
the mean hd duration was 46  74.3 months ( 0482 ) . in total , 61.4% of our patients were caucasian , 11.5% were black , and 27.1% of other origins .
patients had a history of diabetes in 25% of the cases and a history of coronary artery disease in 30.5% .
echocardiographic data from baseline showed hypertrophic cardiomyopathy , dilated cardiomyopathy , and altered lvef in 25.4 , 7.2 , and 23% of the cases , respectively .
the mean follow - up was 12.5 months ( 218 ) , during which 44 ( 18.6% ) patients developed a chf event , of which 22 patients required hospitalisation and 22 patients required a session of additional dialysis in our centre .
the length of hospitalisation was 8.64  6.1 days ( 121 ) , depending on the need for further exploration or the patient 's general condition .
table 1 provides a comparison of the patients baseline characteristics according to their evolution with or without a chf event .
baseline nt - probnp levels were significantly higher among patients who subsequently developed a chf event than among those who did not ( 2,438 vs. 7,982
patients who developed a chf event had significantly more dilated cardiomyopathy ( 18.2 vs. 4.7% , respectively ) and/or altered lvef ( 47.7 vs. 17.2% , respectively ) at baseline compared with patients who did not develop a chf event .
the body mass index was lower in the group of patients who subsequently developed a chf event .
the graphical representation of the evolution of nt - probnp before a chf event showed a clear increase of the biomarker during the months preceding the chf event ( fig .
the regression analysis showed that this difference of evolution was statistically significant ( p < 0.05 ) for the measurement during approximately the 2 months preceding the event .
the proportion of the increase or decrease in nt - probnp measured at two consecutive visits was assessed as a predictor of a chf event ( fig .
the auc was 0.80 . if the threshold of positivity was chosen in favour of specificity , then , at 20% of the relative increase in nt - probnp , the sensitivity of the test was 0.57 and the specificity 0.77 . if the threshold was chosen in favour of sensitivity , then , if all positive relative changes were considered as predictors , the sensitivity was 0.97 but at the price of a low specificity of 0.59 .
only 1 patient had a decrease in nt - probnp between the two last visits before a chf event .
these data show that the relative change in nt - probnp plasma levels is a significant risk predictor of a chf event .
all patients were monitored by monthly nt - probnp plasma level measurements . a relative increase of 20% in nt - probnp measurements
was associated with a risk of developing a chf event during the next month , with a sensitivity of 0.57 and a specificity of 0.77 , given by the roc curve analysis . of note ,
baseline nt - probnp levels were higher among patients who suffered a chf event than among those who did not .
wang et al .   made similar observations and concluded that baseline nt - probnp measurement was an important risk predictor of cardiovascular congestion in peritoneal dialysis patients ; the baseline nt - probnp level was noted to be at least 3-fold higher among patients who developed subsequent circulatory congestion .
however , the present data on monitoring serial nt - probnp measurements provide more important prognostic information that could potentially be used for assessing treatment adequacy and adjusting therapy in the hd population .
if all positive relative changes were considered as predictors of a chf event , the sensitivity would be high and the specificity of the test by roc analysis would be 0.59 . although the specificity is not so high , we know that inflammation , malnutrition , and anaemia are significantly related to nt - probnp levels .
gutierrez et al .   measured baseline nt - probnp concentrations in incident hd patients and calculated the change in concentrations after 3 months in a subset of 585 patients .
patients with the greatest increase in nt - probnp after 3 months of dialysis had a 2.4-fold higher risk of mortality than those with the greatest decrease in nt - probnp .
interestingly , a change in weight was only weakly associated with changes in nt - probnp in the univariate analysis , and this association was attenuated in the multivariate - adjusted analysis .
these data suggest that monitoring nt - probnp not only reflects fluid volume overload but also myocardial damage .
an increased bnp level is a sensitive marker of lv diastolic dysfunction in hd patients .
thus , in addition to monitor nt - probnp levels , other methods assessing dry weight should be performed , including clinical examination , bioimpedance analysis , and relative plasma volume monitoring .
have reported that bnp and interdialytic fluid retention are independent and incremental predictors of mortality in hd patients .
dry weight is a very subjective parameter based first on clinical examination and blood pressure .
patients with altered lv function suffer from anorexia , and , in our study , the body mass index was lower in the group of patients who subsequently developed a chf event .
for these patients , it could be difficult to determine the clinically overload status and the risk of chf event . whereas there is growing enthusiasm for longitudinally following natriuretic peptide concentrations in patients with cardiac failure to help guide therapy
, it is unclear whether employing a similar strategy would be advantageous in hd patients .
prospective randomised studies are needed to determine the cost analysis and cost - effectiveness of nt - probnp - guided therapy in the hd population .
a dynamic change in the nt - probnp plasma level is an important risk predictor of chf events .
we showed an increase of nt - probnp concentrations before the occurrence of a chf event in hd patients .
prospective randomised studies are needed to determine whether specific therapeutic interventions driven by longitudinal changes in nt - probnp can significantly improve outcomes in hd patients .
 backgroundcross - sectional studies have shown that b - type natriuretic peptide ( bnp ) and its n - terminal fragment ( nt - probnp ) are predictive of cardiovascular death in haemodialysis ( hd ) patients . in the present study , 
 we tested the hypothesis that monitoring nt - probnp measurements adds further prognostic information , i.e. predicts congestive heart failure ( chf ) events.methodsin a prospective cohort of 236 hd patients , nt - probnp levels were measured monthly during 18 months . patients were divided according to the occurrence of chf events . in a nested case - control study , 
 we assessed the evolution of nt - probnp levels.resultson average , the 236 hd patients were followed up for 12.5 months , a period during which 44 patients developed a chf event ( half requiring hospitalisation ) . at baseline , 
 patients who developed a chf event had significantly more dilated cardiomyopathy and/or altered left ventricular ejection fraction and higher nt - probnp levels compared with patients who did not develop a chf event . during follow - up , we observed a significant increase in nt - probnp levels preceding the chf event . at a 20% relative increase of nt - probnp , 
 the sensitivity of nt - probnp as a predictor of chf events was 0.57 and the specificity 0.77.conclusionthe relative change in nt - probnp levels is a significant risk predictor of a chf event . 
Introduction
Patients and Methods
Study Design and Study Population
Studied Variable: NT-proBNP
Outcome: CHF Events
Potential Confounding Factors
Statistical Analysis
Results
Patient Characteristics
Outcomes
Change in NT-proBNP as a Predictor of CHF Events
Relative Change in NT-proBNP as a Predictor for Clinical Practice
Discussion
Conclusion
Disclosure Statement