B-type Natriuretic Peptide – Not Only a Biomarker
multinational study, a landmark study that involved 1,586 patients with dyspnoea, Maisel et al.8
showed that a BNP concentration
>100 pg/ml had 83 % accuracy for the clinical diagnosis of HF. The International Collaborative Of NT-proBNP (ICON) Study9
comprised 720
patients with acute HF as the primary cause of their shortness of breath, whereas in another 536 patients, other causes for acute dyspnoea were diagnosed. The study suggested that, for the exclusion of acute HF, a general age-independent cut-point of 300 pg/ml should be used, whereas for diagnosis of HF, age-dependent cut-points are more useful: namely NT-proBNP >450 pg/ml for patients <50 years; >900 pg/ml for patients in between 50 and 75 years; and NT-proBNP >1,800 for patients >75 years.
In the Brain natriuretic peptide for acute shortness of breath evaluation (BASEL) study, Mueller et al.10
showed that the use of
BNP levels significantly reduced the need for hospital admission (75 % versus 85 %) or to intensive care (15 % versus 24 %). Time to discharge was also reduced in the BNP group compared with the control group (8 days versus 11 days), without the trade-off of increased rehospitalisation, resulting in a significant cost reduction of 26 %. Similarly, the Improved Management of patients with congestive heart failure (IMPROVE CHF) study11
validated this point
Levels of natriuretic peptides might be elevated meaningfully in women and in people over 60 years of age who do not have HF; thus, these levels should be interpreted cautiously in such individuals when distinguishing between cardiac and non- cardiac causes of dyspnoea.4
for NT-proBNP. BNP levels tend to be less elevated in HF with preserved EF than in HF with low EF, and are lower in patients who are obese.4
BNP levels are also elevated in patients with pulmonary diseases, at least in those with concomitant RV dysfunction.12
They increase in
proportion to the severity of RV dysfunction and could be a useful indicator of this condition.13
In patients with RV pressure overload
owing to primary pulmonary hypertension and thromboembolism, plasma BNP levels correlate with mean pulmonary artery pressure, right atrial pressure, RV end-diastolic pressure and total pulmonary resistance.13
In addition, plasma BNP levels are augmented in some subjects with COPD undergoing exacerbations21,25
Elevated levels of NT-proBNP are and, in any case, the period until
initial COPD exacerbation in subjects with a high plasma BNP level seems to be significantly shorter.21
Interestingly, in patients with chronic pulmonary hypertension, an increase in BNP not only correlates with the degree of RV dysfunction, but also with the risk of mortality.14
Moreover, high
BNP concentrations resulting from pulmonary hypertension secondary to end-stage lung disease have been reported,13 the absence of LVF.15
Elevated BNP concentrations identify significant
pulmonary hypertension with a sensitivity of 85 % and specificity of 88 % and predicted mortality.15
Elevated BNP levels have been found in patients with hypoxaemia and COPD, particularly in patients with cor pulmonale when compared with patients with COPD alone. Hypoxemia seems to be more severe in patients with higher BNP levels than in those with lower BNP levels.16
In chronic lung disease, hypoxia is supposed to be the most important factor in the development of pulmonary hypertension. Interestingly, NT-proBNP was highly elevated in patients with chronic hypercapnic respiratory failure and correlated with the degree of respiratory impairment.17
BNP concentrations are higher in patients with chronic respiratory failure complicated by cor pulmonale. The specificity and sensitivity of the plasma BNP concentration for detecting cor pulmonale have been reported to be 73.3 % and 100 %, respectively.18
The BNP Consensus EUROPEAN RESPIRATORY DISEASE even in
This latter finding suggests that cardiac involvement in exacerbations of COPD is an important determinant of prognosis.26
In any case, the
overall diagnostic ability of both NT-proBNP and BNP are lower for detecting HF in stable patients with chronic dyspnoea and a diagnosis of COPD than in patients with acute dyspnoea presenting at the emergency department.28
Unfortunately, the pathophysiological consequences of these elevated concentrations in COPD are not completely understood, although the intravascular application of exogenous BNP has been shown to blunt acute hypoxic pulmonary vasoconstriction in rat lungs29
and healthy volunteers.30
vasodilation in patients with chronic cor pulmonale.31 exerts antiproliferative effects in vitro32
In addition, BNP caused pulmonary Moreover, BNP
remodelling process in chronically hypoxia-exposed rats.33
and attenuates the In two
models of non-hypoxia-mediated pulmonary vasoconstriction, BNP induced cyclic guanosine monophosphate (cGMP) and led to vasodilation during either intravascular or aerosol application.34
81
strong predictors of early mortality among patients admitted to hospital with acute exacerbations of COPD independently of other known prognostic indicators.26
NT-proBNP levels <587.9 pg/ml in
patients with acute exacerbations of chronic pulmonary diseases were associated with favourable one-year outcomes.27
Panel guidelines state that cor pulmonale is associated with an intermediate elevation of BNP, typically ranging from 100 to 500 pg/ml.19
Levels <100 and >500 pg/ml have high negative and positive predictive values, respectively, for HF. Between these thresholds, a Bayesian approach is warranted, using BNP to corroborate the clinical evaluation. The increase in BNP and NT-proBNP might be useful as a marker of severity and, therefore, as a prognostic indicator of COPD and chronic cor pulmonale, because this increase reflects water–electrolyte imbalances produced by hypoxia and pulmonary vein and right chamber distension.20
Intriguingly, plasma BNP levels are also elevated in patients with stable COPD without pulmonary hypertension or cor pulmonale, although there is a significant correlation between plasma BNP level and % ejection fraction and pulmonary artery systolic pressure;21
normal RV function after exercise.22
they are also increased in patients with COPD with van Gestel et al. demonstrated
that COPD is associated with elevated plasma NT-proBNP levels in patients undergoing vascular surgery with a normal LV systolic function.23
Even patients with mild COPD were three times more likely to have had elevated NT-proBNP levels than those without COPD, whereas those with severe disease were approximately six times more likely to have had elevated NT-proBNP levels. Importantly, elevated NT-proBNP levels were associated with increased risk of death in patients with COPD independent of well- established risk factors, such as smoking status and age. Recent research has documented that NT-proBNP predicts survival, but not hospital admission in patients with COPD.23
The ability of NT-proBNP
to predict death or hospitalisation independently is superseded by the presence of a dilated left atrium, aortic stenosis and LV systolic dysfunction.24
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