NT-ProBNP Adds Prognostic Value in NSTE-ASC

July 16, 2009

July 16, 2009 (Uppsala, Sweden) — N-terminal pro-brain natriuretic peptide (NT-proBNP) was the only one of a panel of biomarkers that added significant prognostic information to conventional risk factors in the six months following non-ST-elevation ACS in a new study [1].

In the study, published in the July 21, 2009 issue of the Journal of the American College of Cardiology, NT-proBNP was independently predictive for adverse outcomes throughout the entire six-month observation period. The authors, led by Dr Kai Eggers (University Hospital Uppsala, Sweden), conclude that NT-proBNP should be considered for improvement of risk stratification during early follow-up in NSTE-ACS patients.

"I think our results are pretty convincing and underline the potential utility of NT-proBNP," Eggers commented to heartwire . "Our study suggested that NT-proBNP was most useful when measured at six weeks."

Focus on Follow-Up Period

Eggers explained to heartwire : "Patients with ACS get very good acute tests and treatment, and several different biomarkers are measured, but after patients are discharged from the hospital, we check their cholesterol and blood pressure but we don't measure anything that gives us an indication of their cardiac state. But patients are still vulnerable at this point. We wanted to see if any of the cardiac biomarkers could be useful to predict risk if measured during follow-up."

To investigate this, they measured NT-proBNP, C-reactive protein (CRP), cardiac troponin I (cTnI), and estimated glomerular filtration rate (eGFR) at randomization and after six weeks and six months in 877 NSTE-ACS patients included in the FRISC II trial. The biomarkers' prognostic value during five-year follow-up was evaluated by three different methods.

Their results showed that NT-proBNP was a strong predictor of adverse events throughout the entire six-month sampling period, and this predictive status remained after other clinical risk indicators, including biomarkers of cardiomyocyte necrosis, inflammation, and renal dysfunction, were taken into account. The authors note that NT-proBNP levels were particularly predictive for mortality, which they suggest is probably because this substance reflects larger infarct size and progressive remodeling and thus a more pronounced degree of myocardial dysfunction.

At randomization, NT-proBNP was the strongest predictor for mortality, while cTnI was the strongest predictor of MI and the composite end point (death/MI). CRP or eGFR at randomization did not provide independent prognostic information.

During follow-up, NT-proBNP was the strongest predictor for mortality and MI, and CRP also became predictive for death and MI, while cTnI and the eGFR provided only limited prognostic value.

When the tested biomarkers were added to prognostic models based on conventional risk indicators, only NT-proBNP at six weeks provided incremental prognostic value, showing a significant increase of the C statistic. At six months, NT-proBNP still showed the greatest increase of the C statistic, but this did not reach statistical significance.

Eggers et al say: "Our findings raise the question of whether and which biochemical markers should be assessed in the stable phase after NSTE-ACS to improve prognostication." They add that measuring NT-proBNP at six weeks might be particularly useful and should allow reclassification of a relative large subset of patients without events to lower categories of risk and enable identification of some high-risk subjects with persistent left ventricular dysfunction after NSTE-ACS in whom optimization of pharmacological treatment is mandatory. They add that testing for CRP could be useful for risk stratification at a later time point (eg, after six months).

But Eggers commented to heartwire that further studies are needed to define the correct threshold of NT-proBNP that signals increase risk. "At the moment we don't have any reference as to what should be defined as a high level. We need a prospective study to look at this."

Reclassifying Patients

In an accompanying editorial [2], Drs Christopher DeFilippi and Stephen Seliger (University of Maryland, Baltimore) point out that Eggers et al's results suggest that measuring NT-proBNP would mean that 11% of patients would be correctly reclassified into higher- or lower risk-categories (mostly lower). "Whether 11% net reclassification justifies the routine measurement of NT-proBNP six weeks after an ACS event depends in part on cost-effectiveness considerations and whether a reclassification to a lower-risk category has the same ramifications for clinical care as reassignment to a higher-risk category," they write.

DeFilippi commented to heartwire : "Several different biomarkers are measured in the acute phase of ACS, each one representing a different pathway in the pathophysiology of the disease. But over time the different pathways may become more or less relevant. People have had a lot of difficulty trying to figure out which marker to measure when. We know that troponins are particularly useful at the beginning. This paper suggests that NT-proBNP may be most helpful when measured during early follow-up, and CRP may be of some use at later follow-up."

But he added that this paper won't change clinical practice by itself. "This is a good start. We know that NT-proBNP at six weeks gives information about risk. But we now need to know what to do with a positive or negative result. Will this change treatment? We need more studies to address this."