Natriuretic peptide levels in plasma can provide clinically relevant information on prognosis and left ventricular function following acute myocardial infarction. Researchers have investigated a number of natriuretic peptides. However, there have been few direct comparisons showing the relative prognostic value of these entities.

Dr. Squire and colleagues have completed a comparison of B-type natriuretic peptide (BNP), N-terminal BNP (N-BNP), N-terminal atrial natriuretic peptide (N-ANP) and C-type natriuretic peptide (CNP). The comparison shows the value of these 4 different natriuretic peptides in predicting death, reinfarction and hospitalization after complicated acute myocardial infarction.

The analysis is part of a neurohormonal substudy of OPTIMAAL (Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan). The main purpose of the trial was to compare losartan to captopril in patients with heart failure or left ventricular dysfunction following acute myocardial infarction.

In the neurohormonal substudy, investigators acquired natriuretic peptide levels for 236 patients. This included 121 patients who received losartan and 115 on captopril. They took measurements at randomization, then at one month, 1 year and 2 years after myocardial infarction.

The mean follow-up was 958 days. There were 14 deaths in the first 30 days following myocardial infarction. An additional 20 deaths occurred after 30 days. There were 40 reinfarctions and 134 hospitalizations.

Temporal Release of Peptides

Investigators found very different patterns of secretion of these 4 peptides after myocardial infarction. This implies that natriuretic peptides are not a homogeneous group of compounds subject to the same stimulus.

Both BNP and N-BNP levels were high within a few days of acute myocardial infarction. There was a steady drop-off at 1 month and 1 year.

Levels of N-ANP exhibited a different pattern. Circulating levels increased significantly between baseline and 1 month. Levels fell somewhat between 1 month and 1 year, but in the following year, there was a significant decrease.

By contrast, CNP levels remained steady between baseline and one month, then fell significantly over 1 year, and increased slightly at the year 2 measurement.

Mortality

Baseline BNP and N-BNP were strong predictors of mortality at 30 days, with p values of 0.001 and 0.004, respectively, according to Dr. Squire. Baseline N-ANP levels were also predictive (p = 0.012), but baseline CNP levels were not. The only baseline measurement that predicted mortality after 30 days was N-BNP (p = 0.05).

Reinfarction

None of the peptides predicted reinfarction over the follow-up period.

Hospitalization During Follow-up

Peptide levels at baseline and 1 month did not predict later hospital days. However, N-BNP level at 1 year was a powerful predictor of the number of hospital days (p < 0.0005).

In addition, the mean number of hospital days was higher among patients who had higher than median levels of N-BNP or N-ANP. However, these findings did not reach statistical significance.

Treatment Outcomes

The change in N-BNP between baseline and 1 month was highly predictive of outcome, according to Dr. Squire. In patients who had positive outcomes past 1 month, n-BNP fell significantly more than for patients who had adverse outcomes thereafter. According to Dr. Squire, this finding indirectly supports work from Japanese investigators indicating that n-BNP may be a marker for efficacy of therapy in heart failure.

Together, these results suggest that baseline levels of BNP and n-BNP strongly predict mortality and unplanned rehospitalization in patients with complicated acute myocardial infarction. Change in N-BNP between baseline and 1 month is also highly predictive of adverse outcomes; in particular, patients with less change over time have worse outcomes.

Both BNP and N-BNP appear to be consistent and powerful predictors of outcomes for patients who have an acute myocardial infarction with evidence of heart failure or left ventricular dysfunction. Measuring plasma levels of these peptides may help further substratify patients into high risk and very-high-risk groups. One day, physicians may use BNP or N-BNP to identify patients who require more intensive or aggressive therapy.