Case 38
Andrew Solomon, Julia Anstey, Liora Wittner, Priti Dutta in Clinical Cases, 2021
NT-proBNP is the inactive fragment of a hormone released by the heart when the ventricles are stretched, for example by fluid overload. The hormone causes fluid and sodium loss in the urine and mild vasodilation. Thus, in theory, a natriuretic peptide would generate natriuresis, utilising a renal mechanism that would ensure salt and fluid loss as a physiological response to the sensation of fluid overload. The serum levels of NT-proBNP have been validated in laboratory assays for diagnostic purposes. NT-proBNP levels are raised in heart failure and increase in level according to the New York Heart Association classification. If NT-proBNP is normal, it has a potential to help reduce the chance of there being heart failure present – with an approximate negative predictive value of 97%.
New treatments for hypertension
H. Gavras in The Year in Hypertension 2004, 2004
This study provides insight into the neurohumoral mechanism mediating the observed haemodynamic effects of vasopeptidase inhibition. In this study, the effect on pre-load was maintained with long-term administration, suggesting that pre-load reduction is an important component of antihypertensive effects of vasopeptidase inhibitors. The combination of reduction in pre-load along with arterial vasodilation may contribute to the more potent antihypertensive effects of vasopeptidase inhibitors when compared with other agents. In contrast to heart failure, in which the activation of natriuretic peptides is more obvious, in this study no increase in plasma natriuretic peptide levels was observed with inhibition of their degradation, perhaps because of the pre-load reduction. Although the significant increase in adrenomedullin levels with short- and long-term omapatrilat therapy may contribute to the arterial vasodilation observed, adrenomedullin has not been shown to reduce pre-load when given alone, even at pharmacological doses associated with a marked hypotensive effect. Thus, other vasodilatory substances such as bradykynin, NO, or prostacyclin, enhanced by dual NEP/ACE inhibition, maybe involved. Finally, these data provide insight into the role of natriuretic peptides, adrenomedullin, and the RAS, and underscore the complexity of these novel antihypertensive agents, suggesting unique features that could potentially result in greater cardioprotective effects than with other drugs.
Cardiovascular responses in pathological situations
Neil Herring, David J. Paterson in Levick's Introduction to Cardiovascular Physiology, 2018
During cardiac failure, the kidneys retain salt and water. The resulting expansion of the extracellular fluid compartment, by up to 30%, contributes to cardiac dilatation and oedema formation. Salt and water retention is caused by the increased renal sympathetic activity, which causes renal vasoconstriction (Figure 18.18) and activates the RAAS. Circulating aldosterone is raised further through reduced degradation in the congested, underperfused liver. Circulating natriuretic factors (NFs) are also raised, due to atrial NF secretion by the distended atria and a big increase in brain NF secretion by the distended ventricles. NFs may have a beneficial role in attenuating the excessive renal retention of salt and water. Raised plasma brain natriuretic peptide is used clinically as a marker of heart failure.
Regulation of circulating chromogranin B levels in heart failure
Published in Biomarkers, 2018
Felix M. Heidrich, Carolin Melz, Mimi S. Buechau, Christian Pfluecke, Silvio Quick, Uwe Speiser, David M. Poitz, Antje Augstein, Tobias Ruf, Nadine K. Wässnig, Akram Youssef, Ruth H. Strasser, Stephan Wiedemann
In terms of potential extra-cardiac confounders on circulating CGB and NT-proBNP levels, age, sex, BMI, renal impairment and PPI medication were assessed. Circulating natriuretic peptide levels are known to be body weight dependent (Wang et al.2004). Obese HF patients are known to have almost three times less BNP and NT-proBNP levels than non-obese patients (McCord et al.2004). False-negative rates of about 15–20% have been shown in obese patients admitted for decompensated HF (Krauser et al.2005). In our study, higher BMI was associated with lower NT-proBNP values and this was confirmed in ANCOVA analysis. On the contrary, CGB levels were independent of body weight. Moreover, BNP and NT-proBNP levels are known to be age dependent with higher values in older individuals (Redfield et al.2002). Notably, we show that CGB levels in HF patients are independent of age. Considering a constantly weight gaining and aging population (Ortega et al.2016), obesity and age are likely to reach more relevance and may complicate interpretation of plasma natriuretic peptide values even more. Additionally, BNP and NT-proBNP levels were shown to be sex dependent with higher plasma levels in healthy women compared to healthy men (Redfield et al.2002). According to our study population, however, neither NT-proBNP nor CGB plasma levels were sex dependent. An overview of known confounders of circulating CGB and natriuretic peptide levels in HF patients is provided (Table 3).
A common humoral background of intraocular and arterial blood pressure dysregulation
Published in Current Medical Research and Opinion, 2018
Janusz Skrzypecki, Iwona Grabska-Liberek, Joanna Przybek, Marcin Ufnal
Natriuretic peptides, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), are a group of compounds that lower BP by producing diuresis, natriuresis, and vasodilation34,35. ANP is produced by miocytes of the right atrium in response to the increased venous return35. BNP is produced by the overstretched ventricles, and is commonly used as a marker of heart failure36. In contrast to ANP and BNP, CNP lacks diuretic activity and decreases BP, causing vasodilation37. Interestingly, levels of natriuretic peptides are increased in hypertension related to volume expansion, e.g. primary hyperaldosteronism, whereas do not change in essential hypertension38.
Novel heart failure biomarkers: why do we fail to exploit their potential?
Published in Critical Reviews in Clinical Laboratory Sciences, 2018
Arnold Piek, Weijie Du, Rudolf A. de Boer, Herman H. W. Silljé
The levels of natriuretic peptides can be influenced by other syndromes and diseases, and kidney dysfunction is an important factor that may elevate natriuretic peptide levels [31]. In addition, obesity may be associated with lower natriuretic peptide concentrations and this may modestly reduce the diagnostic sensitivity in morbidly obese patients [32]. Importantly, with the positive results of clinical HF trials with entresto (LCZ-696) [33,34], the introduction of this drug in daily clinical HF practice will make the interpretation of BNP levels in such treated patients more difficult. Entresto is made up of the angiotensin-receptor blocker (ARB), valsartan, and the neprilysin inhibitor prodrug, sacubitril; the latter inhibits degradation of natriuretic peptides, thereby enhancing their beneficial effect during cardiac stress [35]. The concept that the lower the BNP levels in chronic HF patients, the better the prognosis during treatment monitoring will no longer hold true in these patients. Because NT-proBNP and MR-proANP are not subject to breakdown by neprilysin, these biomarkers can still be used for patient monitoring in this setting [36].
Related Knowledge Centers
- Atrial Natriuretic Peptide
- Cyclic Guanosine Monophosphate
- Circulatory System
- Hormone
- Brain Natriuretic Peptide 32
- Urodilatin
- Kidney
- Dendroaspis Natriuretic Peptide
- Heart Failure
- Npr1