Page 117 - Biomarkers for risk stratification and guidance in heart failure

Chapter 5
We show that 1 month after hospital discharge, change in NT-proBNP has prognostic power similar to the absolute NT-proBNP concentration measured at 1 month for prediction of mortality (Table 3 ). For prediction of the combined end point of HF readmission or mortality, early outpatient change in NT-proBNP is clearly superior to the absolute concentration at 1 month (Wald 20.5 vs 6.1, respectively; Table 3 ). Thus it seems that in patients at highest risk for events (outpatient destabilized HF and early after admission because of acute HF), a change in NT-proBNP concentration between 2 measurements at relatively short interval is an important predictor for events, and clinical stability cannot be assumed by only 1 NT-proBNP measurement.
Prognostic Importance of Small Changes in NT-proBNP Concentration 1 Month After Hospital Discharge
Changes in natriuretic peptide concentrations may reflect changes in cardiac wall stress and cardiac performance, but may also depend on the biologic variability of these biomarkers. For NT-proBNP, biologic variability has been assessed in chronic HF patients at different time intervals (within-day, week-to-week, 1 to 3 months, and year-to year7,15-19). Short term biologic variability in terms of reference change values (RCVs) differed widely among studies published, varying from 23%19 to 98%,7 suggesting that changes in NT-proBNP concentration even up to 100% may be safely accepted. Our finding that small changes in NT-proBNP concentration (ie, <30%) early after hospital discharge are of prognostic importance challenges these interpretations of so-called “biologic variability” of NT-proBNP. The high RCVs found in the previously mentioned studies are controversial because they appear to be related to the skewed distribution of measured NT-proBNP values and improve after normalizing transformation of the data.16 Also, median NT- proBNP concentrations in studies assessing biologic variability of NT-proBNP were relatively low (579-1,323 pg/mL)15,16 and biologic variability has been shown to decrease with elevating NT-proBNP concentration.15 Furthermore patient numbers were limited in these studies (20-78 patients).18,19 Most importantly, these studies assumed that their patients were in a stable condition based on clinical characteristics and on their stability in the past, but did not take into account the long-term survival after measurement of NT-proBNP concentration. Moreover, it was assumed that clinical stability can easily be assessed without in-depth diagnostic testing, which is most likely not the case. Therefore, objective evidence of clinical stability was lacking and subclinical changes in NT-proBNP
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