Incidence of normal values of natriuretic peptides in patients with chronic heart failure and impact on survival: A direct comparison of N-terminal atrial natriuretic peptide, N-terminal brain natriuretic peptide and brain natriuretic peptide

1. Brain natriuretic peptide is a new natriuretic hormone with striking similarity to atrial natriuretic peptide, but there are no previous data concerning its clearance in man. Two pathways of clearance for atrial natriuretic peptide are recognized: degradation by neutral endopeptidase and binding to atrial natriuretic peptide clearance receptors. We have examined the effect of candoxatril, an inhibitor of neutral endopeptidase (dose range 10–200 mg), and the effect of an infusion of a pharmacological dose [45 μg (90 μg in two patients)] of synthetic human atrial natriuretic peptide on plasma human brain natriuretic peptide-like immunoreactivity levels in seven patients with mild to moderate chronic heart failure. 2. Plasma human brain natriuretic peptide-like immunoreactivity levels were elevated in all patients (mean ± sem 22.0 ± 6.2 pmol/l) compared with healthy control subjects (1.3 ± 0.2 pmol/l, n = 11). 3. In all patients, candoxatril increased both plasma atrial natriuretic peptide (P < 0.05) and plasma human brain natriuretic peptide-like immunoreactivity (P < 0.05) levels. 4. By contrast, an exogenous infusion of atrial natriuretic peptide had no effect on plasma human brain natriuretic peptide-like immunoreactivity levels despite increasing the plasma atrial natriuretic peptide concentration to 424 ± 74 pmol/l, which is a level of atrial natriuretic peptide which would have ‘swamped’ all atrial natriuretic peptide clearance receptors. 5. We have therefore shown that plasma human brain natriuretic peptide-like immunoreactivity levels in chronic heart failure are increased by a neutral endopeptidase inhibitor, but are unchanged by an exogenous infusion of atrial natriuretic peptide. Our results suggest that in patients with chronic heart failure, degradation by neutral endopeptidase is an important pathway for clearance of brain natriuretic peptide. By an indirect approach, we did not find any evidence of a role for atrial natriuretic peptide clearance receptors in the metabolism of brain natriuretic peptide in these patients. Although this is in agreement with work in vitro, there could be alternative explanations for the lack of a change in circulating human brain natriuretic peptide-like immunoreactivity during exogenous administration of atrial natriuretic peptide.

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Evaluation of Atrial Natriuretic Peptide and Brain Natriuretic Peptide in Atrial Granules of Rats with Experimental Congestive Heart Failure

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215540104901012 ◽

2001 ◽

Vol 49 (10) ◽

pp. 1293-1300 ◽

Cited By ~ 16

Author(s):

Gad M. Bialik ◽

Zaid A. Abassi ◽

Ilan Hammel ◽

Joseph Winaver ◽

Dina Lewinson

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Atrial Natriuretic Peptide ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Aortocaval Fistula ◽

Granule Formation ◽

Gold Particles ◽

The Mean ◽

Atrial Natriuretic

The natriuretic peptides are believed to play an important role in the pathophysiology of congestive heart failure (CHF). We utilized a quantitative cytomorphometric method, using double immunocytochemical labeling, to assess the characteristics of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in atrial granules in an experimental model of rats with CHF induced by aortocaval fistula. Rats with CHF were further divided into decompensated (sodium-retaining) and compensated (sodium-excreting) subgroups and compared with a sham-operated control group. A total of 947 granules in myocytes in the right atrium were analyzed, using electron microscopy and a computerized analysis system. Decompensated CHF was associated with alterations in the modal nature of granule content packing, as depicted by moving bin analysis, and in the granule density of both peptides. In control rats, the mean density of gold particles attached to both peptides was 347.0 ± 103.6 and 306.3 ± 89.9 gold particles/μm2 for ANP and BNP, respectively. Similar mean density was revealed in the compensated rats (390.6 ± 81.0 and 351.3 ± 62.1 gold particles/μm2 for ANP and BNP, respectively). However, in rats with decompensated CHF, a significant decrease in the mean density of gold particles was observed (141.6 ± 67.3 and 158.0 ± 71.2 gold particles/μm2 for ANP and BNP, respectively; p < 0.05 compared with compensated rats, for both ANP and BNP). The ANP:BNP ratio did not differ between groups. These findings indicate that the development of decompensated CHF in rats with aortocaval fistula is associated with a marked decrease in the density of both peptides in atrial granules, as well as in alterations in the quantal nature of granule formation. The data further suggest that both peptides, ANP and BNP, may be regulated in the atrium by a common secretory mechanism in CHF.

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Plasma atrial natriuretic peptide (ANP) fragments proANP (1–30) and proANP (31–67) measurements in chronic heart failure: a useful index for heart trasplantation?

Clinica Chimica Acta ◽

10.1016/s0009-8981(01)00520-4 ◽

2001 ◽

Vol 310 (1) ◽

pp. 49-52 ◽

Cited By ~ 9

Author(s):

Enrico Cappellin ◽

Rosalba Gatti ◽

Paolo Spinella ◽

Carlo B De Palo ◽

Wolfgang Woloszczuk ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Plasma Atrial Natriuretic Peptide ◽

Atrial Natriuretic

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Abstract 2793: Comparison of Midregional Pro-atrial Natriuretic Peptide, B-type Natriuretic Peptide, and Amino-terminal Pro-B-type Natriuretic Peptide in Patients with Chronic Heart Failure: Influencing Factors, Detection of Left Ventricular Systolic Dysfunction, and Prediction of Death

Circulation ◽

10.1161/circ.116.suppl_16.ii_620-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Deddo Moertl ◽

Martin Huelsmann ◽

Joachim Struck ◽

Andreas Gleiss ◽

Alexandra Hammer ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Influencing Factors ◽

Natriuretic Peptides ◽

Left Ventricular Systolic Dysfunction ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Ventricular Systolic Dysfunction

Background: Although natriuretic peptides are increasingly used for the management of chronic heart failure (CHF), there are sparse comparative data. Therefore, we compared the importance of influencing factors, the ability to detect left ventricular systolic dysfunction, and the prognostic power of midregional pro-atrial natriuretic peptide (MR-proANP), B-type natriuretic peptide (BNP), and aminoterminal pro-B-type natriuretic peptide (NT-proBNP) in patients with chronic heart failure. Methods and Results: MR-proANP, using a new assay directed at the midregion of aminoterminal-proANP, was compared with BNP and NT-proBNP, using conventional assays, in 797 patients with CHF. All three natriuretic peptides were independently influenced by left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and the presence of ankle edema. Area under receiver-operator characteristic curves for detection of an LVEF <40% were similar between MR-proANP (0.799 [0.753– 0.844]) and BNP (0.803 [0.757– 0.849]), and NT-proBNP (0.730 [0.681– 0.778]. During a median observation time of 68 months, 492 patients died. In multiple Cox regression analysis each natriuretic peptide was the strongest prognostic parameter among various clinical variables, but proportion of explained variation showed that NT-proANP was a significantly stronger predictor of death than NT-proBNP and BNP (Figure ). Conclusions: Despite similarities in influencing factors and detection of reduced LVEF, MR-proANP outperformed BNP and NT-proBNP in the prediction of death. A new assay technology and the high biological stability of MR-proANP are potential explanations for these findings.

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