Natriuretic Peptides Improve Risk Assessment in Low-Risk Coronary Diseases

LORENSKOG, Norway, July 10 -- B-type natriuretic peptides have earned a new vote of confidence as a prognostic biomarker for low-risk patients with stable coronary disease.

A new analysis of data from a multicenter clinical trial showed that measuring BNP in these patients, when added to conventional risk factors, enhances prognostic assessment, concluded Torbjorn Omland, M.D., Ph.D., of Akershus University Hospital in Lorenskog, and international colleagues, in the July 17 issue of the Journal of the American College of Cardiology.

Rising levels of BNP independently predicted an increased risk of fatal or nonfatal heart failure, they reported online. N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicted the risk of cardiovascular mortality, fatal or nonfatal heart failure, and fatal or nonfatal stroke. Neither biomarker accurately predicted a patient's risk of myocardial infarction.

"BNP and NT-proBNP significantly improved the predictive accuracy of the best available model for incident heart failure, and NT-proBNP significantly improved the model for cardiovascular death," said Dr. Omland.

They went on to state that the data "support measurement of BNPs in low-risk populations for prognostic assessment but do not provide a mandate for the use of these peptides for tailoring therapy for individual patients."

The findings came from an analysis of data from the Prevention of Events With Antiogensin-Converting Enzyme Inhibition (PEACE) trial. BNP and NT-proBNP have proven to be predictive of short- and long-term survival in patients with acute coronary syndromes. However, the peptide fragments' prognostic value in low-risk coronary-disease patients had remained unresolved.

For the current study, Dr. Omland and colleagues evaluated 3,761 PEACE patients who had plasma samples available for measurement of the BNPs obtained prior to randomization. Baseline characteristics of these patients did not differ from those of the remaining 4,529 PEACE patients who were excluded from the analysis. The primary objective was to examine the association between natriuretic peptide concentrations and the rate of cardiovascular mortality, fatal or nonfatal myocardial infarction, heart failure, and stroke.

After a median follow-up of 4.8 years, the total number of events consisted of 127 cardiovascular deaths, 104 fatal or first nonfatal heart failure events, 241 fatal or first nonfatal acute MI events, and 86 fatal or first nonfatal stroke events.

In a univariate analysis, BNP and NT-proBNP predicted the risk of cardiovascular mortality, fatal or nonfatal stroke, and fatal or nonfatal heart failure. After adjustment for conventional cardiovascular risk factors, BNP remained an independent predictor of heart failure events (hazard ratio 1.62, P<0.001). NT-proBNP predicted the risk of cardiovascular mortality (HR 1.69, P<0.001), heart failure (HR 2.35, P<0.001), and stroke (HR 1.63, P<0.001).

The investigators found that NT-proBNP outperformed BNP for all of the endpoints assessed except fatal and nonfatal MI, for which neither of the two biomarkers proved to be an independent predictor.

The study did not identify a specific cutoff value for risk stratification. In fact, the authors stated that "the risk associated with increasing BNP and NT-proBNP concentrations is largely monotonic and does not allow definition of a specific threshold value." They also pointed out that cutoff values for heart failure were derived from trials of acutely dyspneic patients. As such, those values should not be viewed as reflecting the upper limit of normal.

The results showed that measurement of BNPs did not identify patients who might benefit from treatment with an ACE inhibitor. The primary purpose of the PEACE trial, which yielded a negative result, was to evaluate the effect of trandolapril on a composite cardiovascular event rate.

In acknowledging the study's limitations, the investigators stated that the subset of patients from the PEACE trial might not reflect all patients with stable CAD. Additionally, plasma samples for the study were contributed by multiple sites, which could influence the consistency of samples and their collection.