What is the role of brain natriuretic peptide (BNP) testing in the evaluation of acute coronary syndrome?

Updated: Jan 08, 2018
  • Author: Donald Schreiber, MD, CM; Chief Editor: Erik D Schraga, MD  more...
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Researchers examined the role of brain natriuretic peptide (BNP) levels as a marker of left ventricular (LV) dysfunction associated with myocardial ischemia in acute coronary syndrome (ACS). In animal studies, the induction of transient hypoxia provoked BNP release without troponin release. Transient BNP elevations are detected during coronary angiography, presumably due to the transient effects of contrast material inhibiting blood flow in the coronary arteries.

A more important finding is that BNP levels are correlated with the extent of ischemic myocardium on stress thallium testing and with the number of diseased vessels detected on coronary angiography. However, BNP levels considerably overlap across study subjects and do not enable sufficient discrimination on their own to rule ACS in or out.

In patients with confirmed ACS, the natriuretic peptides may have a role in risk stratification. NT-proBNP levels were measured in 1791 patients with non–ST-elevation ACS at presentation and were measured again 48 and 72 hours later. [57] The measurements were related to adverse outcome measures of death and/or myocardial infarction (MI) within 7 and 30 days. After adjustment for other risk factors, a baseline NT-proBNP level of greater than 250pg/mL was associated with an adverse cardiac event.

Furthermore, in patients without troponin elevation (ie, those with unstable angina without MI), a high NT-proBNP level portended the same cardiac risk as it did in patients with MI and elevated troponin levels. In addition, patients with persistently elevated NT-proBNP levels over 72 hours had a worsened 30-day prognosis.

Patients with ACS and clinical signs of congestive heart failure (CHF) at presentation are well known to have an increased risk of adverse cardiac events. Therefore, the finding that patients with ACS and elevated natriuretic peptide levels as markers of CHF on admission also have a high risk for adverse cardiac events was not surprising.

In another study, researchers examined the utility of such risk stratification in 1676 patients with non–ST-elevation ACS. [58] Patients were randomly assigned to receive early invasive or conservative management. BNP levels greater than 80pg/mL were predictive of adverse cardiac outcomes beyond those predicted on the basis of troponin levels alone (even after as long as 6 months). However, treatment strategies did not significantly differ when retrospectively stratified by BNP level.

The same researchers found that a BNP cutoff of greater than 80pg/mL at presentation in patients with ST-elevation and non–ST-elevation ACS was predictive of an increased cardiac mortality risk or the onset of CHF at 4 and 12 months. In this study, part of the A to Z trial, the investigators analyzed serial BNP levels in more than 3000 patients presenting with ST-elevation and non–ST-elevation ACS. [59]

Another group evaluated a single baseline NT-proBNP level on admission in 755 patients with non–ST-elevation ACS. [60] Elevated levels predicted a heightened risk of cardiac mortality at 40 months, even after adjustment for clinical background factors, electrocardiographic (ECG) findings, and elevated troponin levels. Compared with the lowest NT-proBNP quartile, patients in the 2nd, 3rd, and 4th quartiles had relative risks of death of 4, 11, and 27, respectively. Although the data were clearly predictive, the role of such information in patient care remains to be determined.

Jernberg et al determined whether NT-proBNP values, in combination with troponin T and interleukin (IL)-6 levels, were predictive of 2-year outcomes in patients randomly selected to receive an early invasive strategy or conservative treatment. [61] Although NT-proBNP was again predictive of long-term outcome, only patients with both elevated NT-proBNP and elevated IL-6 concentrations had a survival benefit with the early invasive strategy. Furthermore, only elevated troponin levels were independently associated with recurrent MI and death from MI.

Similar prognostic value was found in 1034 patients with CAD symptoms who were referred for coronary angiography. [62] Compared with patients with NT-proBNP levels in the lowest quartile, those patients with levels in the highest quartile were older; they had lower left ventricular ejection fractions (LVEFs) and estimated creatinine clearances; and they were more likely to have a history of MI, clinically significant coronary artery disease (CAD), and diabetes.

In the group of study subjects, the NT-proBNP level added prognostic information beyond conventional risk factors, (age, sex, personal history of CAD, family history of CAD, hypertension, diabetes, smoking status), creatinine clearance, BMI, lipid levels, LVEF, and clinically significant CAD on angiography. Similar findings were uncovered in a substudy analysis of the Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease (FRISC)–II data. [63]


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