Received on April 18, 2008
Accepted on October 29, 2008

Proteomics and Protein Markers

Only Large Reductions in Concentrations of Natriuretic Peptides (BNP and NT-proBNP) Are Associated with Improved Outcome in Ambulatory Patients with Chronic Heart Failure

¹ Cardiovascular Division, Mayo Medical Center, Rochester, MN
² Department of Biostatistics, Mayo Medical Center, Rochester, MN
³ Cardiovascular Division, Mayo Medical Center, Rochester, MN, and Department of Laboratory Medicine and Pathology, Mayo Medical Center, Rochester, MN

^* To whom correspondence should be addressed. E-mail: miller.wayne{at}mayo.edu.

BACKGROUND: Concentrations of B-type natriuretic peptides (BNPs), including N-terminal probrain natriuretic peptide (NT-proBNP), can be used to estimate prognosis in chronic heart failure. Large biologic variability, however, limits the usefulness of serial measurements in individual patients. As a result, the magnitude of change in peptide concentrations that is clinically meaningful remains to be established.

METHODS: We studied 172 New York Heart Association class III–IV outpatients. Primary endpoints were death/transplantation or heart failure hospitalization. The magnitude of peptide changes was categorized as no change (<20% increase or decrease from enrollment), 20% to 80% increase or decrease; and >80% increase or decrease. Changes were also assessed using cutpoints (500 ng/L for BNP and 1000 ng/L for NT-proBNP).

RESULTS: Fifty-two patients died or received transplants during the course of the study. Risk reduction for heart failure hospitalization was demonstrated only for BNP decreases of >80% from enrollment [hazard ratio (HR) 0.318, P = 0.0315]. BNP increases from less than to more than the prespecified cutpoint of 500 ng/L were associated with increased mortality risk (HR 2.101, P = 0.0069), whereas decreases from more than to less than the cutpoint did not reduce risk. NT-proBNP decreases from more than to less than the cutpoint of 1000 ng/L were associated with reduced risk of death/transplantation (HR 0.119, P = 0.0354).

CONCLUSIONS: BNP increases from less than to more than the cutpoint were associated with increased risk of events, whereas further increases did not add to risk. In contrast, only substantial natriuretic peptide decreases (>80%) reduced risk. These data suggest that only robust decreases in natriuretic peptide concentrations should be targeted to reduce mortality and heart failure–related hospitalizations.