Natriuretic peptides are hormones produced in the heart that serve as vasodilators and play a critical role in regulating fluid volume homeostasis. These peptides feature a similar amino acid ring structure that likely contributes to their biological activity. Atrial myocytes synthesize the precursor prepro atrial natriuretic peptide (ANP), which is a 151 amino acid polypeptide, that is stored in intracellular granules as the 126 amino acid proANP . In response to hypervolemic states, the atrial myocytes release proANP, which is converted by the cardiac transmembrane serine protease corin to the active 28 amino acid C-terminal ANP and N-terminal (NT)-proANP . Brain natriuretic peptide (BNP) is generated in a similar fashion and contains similar properties to ANP. Although also synthesized in the brain (as the name implies), BNP was shown to be largely produced by the ventricle, while ANP is produced in the atria . Even though both ANP and BNP have relatively short half-lives, the N-terminal portions of both proANP and proBNP have larger molecular weights and longer half-lives so are more reliable biomarkers as they are easier to measure in the plasma. While NT-proANP and NT-proBNP are typically thought of as biomarkers for heart failure , these biomarkers have been shown to predict long-term mortality and major adverse cardiovascular events (MACE) in patients with stable coronary artery disease and in patients undergoing primary percutaneous coronary intervention (PCI) . Early studies suggested that ANP may have a cardioprotective role and reduced reperfusion injury and reduced infarct size . BNP levels on admission with ST-elevation myocardial infarction were shown to not only predict clinical outcomes but also myocardial perfusion and angiographic success .

Natriuretic peptides may also serve as prognostic biomarkers in patients when checked prior to undergoing non-emergent PCI . Furthermore, trending NT-proBNP correlated with the magnitude of periprocedural myocardial injury in the JUMBO-TIMI 26 trial . Thus, these biomarkers may serve as a better periprocedural biomarker than troponin, which has been shown to have limited value as a predictor of adverse outcomes for patients with periprocedural myocardial injury following PCI . In this issue of the journal, Nicolli and colleagues present a study assessing the value of pre-procedural levels of NT-proANP and NT-proBNP in 395 patients with stable angina and non-ST-elevation acute coronary syndrome (NSTE-ACS) who underwent PCI with stent placement. Patients who experienced MACE during the mean follow-up of 4 years had higher NT-proANP and NT-proBNP compared with patients who did not experience MACE during follow-up. Importantly, although there was correlation between pre-procedural NT-proANP and NT-proBNP levels, the authors did not find significant collinearity. This was important as multivariate analysis found that only NT-proANP levels were significantly associated with MACE, while NT-proBNP levels did not remain independently associated with MACE. This raises the question of whether biomarkers reflecting ANP levels are superior to those reflecting BNP levels in patients undergoing PCI for prediction of MACE. Though the majority of patients were undergoing PCI for NSTE-ACS, there were some important limitations. First, patients with a history of chronic heart failure and valvular disease were excluded as elevation of these biomarkers may be a result from these disease states. Furthermore, patients with chronic inflammatory disease were also excluded. Finally, this study excluded patients undergoing primary PCI for ST-elevation myocardial infarction due to the difficulty in obtaining consent prior to collection of plasma. While this study is limited as it is in a smaller number of patients, it highlights the need to compare the relative prognostic value of multiple biomarkers in patients undergoing PCI to better predict outcomes. This paper serves as an important reminder that although we often utilize biomarkers and try to simplify our understanding of them, there may be important subtle differences that can be associated with differential prediction of outcomes.