Editorial
B-type Natriuretic Peptide – Not Only a Biomarker Mario Cazzola1,2
and Maria Gabriella Matera3
1. Chief, Unit of Respiratory Clinical Pharmacology, Department of Internal Medicine, University of Rome Tor Vergata; 2. Consultant, Department of Pulmonary Rehabilitation, San Raffaele Pisana Hospital, IRCCS; 3. Unit of Pharmacology, Department of Experimental Medicine, Second University of Naples
Abstract
B-type natriuretic peptide (BNP) and its inactive byproduct N-terminal-proBNP (NT-proBNP) are regarded as biomarkers because they function as indicators of increased ventricular mass and a surrogate marker for heart failure. BNP levels are also elevated in patients with pulmonary disease, at least in those with concomitant right ventricular (RV) dysfunction, such as patients with chronic respiratory failure complicated by cor pulmonale. Intriguingly, plasma BNP levels are also elevated in patients with stable chronic obstructive pulmonary disease (COPD) without pulmonary hypertension or cor pulmonale. In addition, plasma BNP levels are augmented in some patients with COPD undergoing exacerbations. Unfortunately, the pathophysiological consequences of these elevated concentrations in COPD are not completely understood, although BNP has an important role in several activities in the lung, such as bronchodilatation, pulmonary permeability and surfactant production; it also blunts acute hypoxic pulmonary vasoconstriction. Recently, we documented the relaxant effect of BNP on isolated human bronchi, particularly after passive sensitisation. We also showed that incubation of human bronchial smooth muscle with BNP inhibited constriction induced by cholinergic and histaminergic stimulation. The bronchial relaxation induced by BNP appears to be associated with the activation of natriuretic peptide receptor (NPR)1 localised on the bronchial epithelium. These findings support a teleological role for elevated BNP concentrations, at least in patients with COPD, in whom BNP might be part of a response aimed at mitigating the effects of the disease. The findings also add important information to current understanding of the local reciprocal interactions of BNP with bronchial tone control and suggest alternative pharmacological options for chronic airway disease therapy, including bronchial asthma or COPD.
Keywords B-type natriuretic peptide, biomarker, heart failure, pulmonary diseases, human isolated bronchi, bronchial relaxant effects
Disclosure: The authors have no conflict of interest to declare. Received: 11 August 2011 Accepted: 1 September 2011 Citation: European Respiratory Disease, 2011;7(2):80–2 Correspondence: Mario Cazzola, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. E:
mario.cazzola@
uniroma2.it
B-type natriuretic peptide (BNP) is a 32-amino acid polypeptide secreted by the cardiac ventricles in response to ventricular volume expansion and pressure overload.1
Although it was first isolated from
the brain, the cardiac ventricles are the main source of BNP. In response to increased myocardial stretch and wall stress, ventricular myocytes secret the pro-hormone pre-proBNP, which is then cleaved into biologically active BNP and the inactive byproduct N-terminal- proBNP (NT-proBNP). The NT-proBNP has a longer plasma half-life and exists at considerably higher concentrations compared with BNP. BNP inhibits renin and aldosterone, decreases sodium retention and increases glomerular filtration rates.2
Moreover, it is regarded as a
biomarker because it functions as an indicator of increased ventricular mass and a surrogate marker for heart failure (HF).2
Biomarkers are
considered to be biological parameters that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention.3
In effect, elevated plasma BNP levels have been associated with reduced left ventricular ejection fraction (LVEF), LV hypertrophy, elevated LV filling pressures, and acute myocardial infarction and ischaemia.4
Observational studies have suggested that, when used in conjunction with other clinical information, BNP (or NT-proBNP) levels
80
are useful in establishing or ruling out the diagnosis of HF in patients with acute dyspnoea.4
A normal BNP level has a high negative
Unfortunately, BNP and NT-proBNP are continuously distributed variables, with some degree of overlap between patients with and without HF.5
predictive value for HF (>95 %), and it helps to exclude cardiac dysfunction as a contributor to dyspnoea, especially in patients with comorbidities.2
The degree of this overlap is not fixed, as it is
influenced by numerous variables in the absence of HF, including normative processes such as age, but also relevant structural heart disease, including abnormalities in heart rhythm, ischaemic heart disease, valvular disease and pulmonary hypertension.5 Accordingly, it should not be surprising that a single cut-point for either peptide is less helpful than considering the markers as continuous variables, where higher concentrations are more likely to be associated with HF and vice versa.5
For both BNP and NT-proBNP to exclude acute HF in patients who are symptomatic, very low values are necessary. For BNP, the value is approximately 20–30 pg/ml,6
has a negative predictive value of 98–99 % is 300 pg/ml.7
whereas for NT-proBNP, a cut point that Values above
these levels, whether or not they are below the rule in cut point, might be associated with HF.5
In the Breathing not properly (BNP) © TOUCH BRIEFINGS 2011
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76