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N-Terminal pro-B-type natriuretic peptide and echocardiographic abnormalities in severely obese patients: correlation with visceral fat.

To the Editor:

B-Type natriuretic peptide (BNP) and its co-released peptide N-terminal propeptide (NT-proBNP) are both secreted mainly by the left cardiac ventricle as a consequence of pressure overload and wall stretch. This situation often occurs in obesity, in which the amount of intraabdominal fat may worsen the severity of morphologic and dynamic cardiac abnormalities detectable by echocardiography (1).

Many studies have confirmed NT-proBNP as a sensitive marker for left ventricular hypertrophy and/or asymptomatic left ventricular dysfunction (2, 3), and it is particularly reliable because of its high negative predictive value (4). To our knowledge, however, recent findings on the relationship between NT-proBNP and morphologic and dynamic cardiac abnormalities in obesity are still inconsistent and controversial. Rivera et al. (5) reported lower NT-proBNP concentrations in obese patients with heart failure compared with nonobese patients. Conversely, Hermann-Annhof et al. (6) found that NT-proBNP concentrations were increased in obese individuals and were comparable to the values for New York Heart Association class I patients. Therefore, to gain further information on the utility of NT-proBNP as an indicator of possible preclinical cardiac disease in normotensive, severely obese individuals, we measured NT-proBNP concentrations in 27 severely obese women with no complications [mean (SD) body mass index, 43.5 (4.8) kg/[m.sup.2] (median, 41.7 kg/[m.sup.2]); mean (SD) age, 33.3 (8.3) years (median, 31 years)] and 15 normal-weight patients. All participants were premenopausal, normotensive, normoglycemic, drug-free young women with normal renal function, who were not dyspneic; this excluded the possibility that high NT-proBNP concentrations might be associated with hypertension and diabetes (7, 8). All patients and controls underwent echocardiography (M-mode color Doppler; VSF Vingmed-System Five; General Electric). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas in the obese group were assessed by computed tomography.

Serum NT-proBNP concentrations were measured by the proBNP (Roche) assay on an Elecsys 2010 analyzer (Roche). Intra- and interassay CVs were 2.7% (at a mean of 176 ng/L) and 5.5% (at a mean of 196 ng/L), respectively.

As recently reported in a similar series (1), obese patients showed impairment of several echocardiographic characteristics compared with lean individuals, and some of these differences correlated significantly with the VAT area. Obese women had higher mean (SD) NT-proBNP concentrations than controls [172.41 (54) vs 56.16 (19.8) ng/L; median, 150 vs 65 ng/L; P <0.001]. Basal NT-proBNP concentrations were also positively correlated with some echocardiographic characteristics (Table 1). Further analysis showed that NT-proBNP concentrations were correlated with the VAT area ([r.sup.2] = 0.60; P <0.0001) and VAT/ SAT ([r.sup.2] = 0.38; P <0.001), but not with SAT (P = -0.61) (9). Fifteen obese patients with a greater amount of visceral fat (VAT >130 [cm.sup.2]) (10) had higher mean NT-proBNP concentrations than those with VAT <130 [cm.sup.2] (n = 12) [mean (SD), 194.13 (14.6) vs 145.25 (10.7) ng/L; median 162 vs 138 ng/L; P <0.02].

Senegen6s et al. (11) confirmed that both animal and human adipose tissue contains natriuretic peptide receptors (NPRs) and suggested that natriuretic peptides may have a lipolytic effect in human subcutaneous adipose cells. However, an interaction between natriuretic peptides and adipose tissue needs an intact NPR system. Moreover, Dessi-Fulgheri et al. (9) reported that expression and synthesis of the natriuretic peptide clearance receptor (NPR-C) in adipose tissue may cause more molecules of circulating A-type natriuretic peptide and BNP to be trapped, thus reducing their biological activity and increasing blood pressure. The lipolytic effect of natriuretic peptides would therefore be reduced, facilitating abdominal fat deposition. In addition, NT-proBNP is not believed to bind NPR-C, and its clearance mechanism is attributed only to the kidney (12). All of these data were obtained in SAT, however, and our findings are concerned with in vivo studies. In fact, we found a relationship of NT-proBNP concentrations with VAT and with VAT/SAT ratio but not with SAT, which supports the different roles of VAT and SAT in producing and processing cytokines and others hormonelike proteins.

The most novel finding in our study is the significant correlation between NT-proBNP and echocardiographic characteristics (left ventricular mass indexed for height, left ventricular mass, end-diastolic posterior wall, end-diastolic septum thickness, myocardial performance index, early diastolic filling wave velocity) in a homogeneous population, even after correction for increased VAT (P <0.05). This may indicate that NT-proBNP itself could serve as an indicator of left ventricular morpho-functional changes. The importance of VAT in influencing cardiac abnormalities and NT-proBNP concentrations in severely obese patients is further sustained by the differences that we observed in these variables when we divided patients on the basis of a VAT cutoff value of 130 [cm.sup.2] (10). The relationship might be reinforced by the fact that our recruitment criteria were designed to avoid confounding factors as much as possible.

In conclusion, although more extensive studies in larger groups of patients are needed, NT-proBNP appears to offer possibilities for identifying preclinical cardiac disease, as already suggested by Hermann-Arnhof et al. (6), particularly in obese women with large amounts of visceral fat.

References

(1.) Morricone L, Malavazos AE, Coman C, Donati C, Hassan T, Caviezel F. Echocardiographic abnormalities in normotensive obese patients: relationship with visceral fat. Obes Res 2002; 10:489-97.

(2.) Yamamoto K, Burnett JC, Jougasaki M, Nishimura R, Bailey K, Saito Y, et al. Superiority of brain natriuretic peptide as marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy. Hypertension 1996;28: 988-94.

(3.) de Lemos JA, McGuire DC, Dranzer MH. B-Type natriuretic peptide in cardiovascular disease. Lancet 2003;262:316-22.

(4.) Pfister R, Scholz M, Wielckens K, Erdmann E, Schneider CA. Use of NT-proBNP in routine testing and comparison to BNP. Eur J Heart Fail 2004;6:289-93.

(5.) Rivera M, Cortes R, Salvador A, Bertomeu V, de Burgos FG, Pay! R, et al. Obese subjects with heart failure have lower N-terminal probrain natriuretic peptide plasma levels irrespective of etiology. Eur J Heart Fail 2005;7: 1168-70.

(6.) Hermann-Arnhof KM, Hanusch-Enserer U, Kaestenbauer T, Publig T, Dunky A, Rosen HR, et al. N-Terminal pro-B-type natriuretic peptide as an indicator of possible cardiovascular disease in severely obese individuals: comparison with patients in different stages of heart failure. Clin Chem 2005;51:138-43.

(7.) Mueller T, Gegenhuber A, Dieplinger B, Poelz W, Haltmayer M. Capacity of B-type natriuretic peptide (BNP) and amino-terminal proBNP as indicators of cardiac structural disease in asymptomatic patients with systemic arterial hypertension. Clin Chem 2005; 51:2245-51.

(8.) Halse KG, Lindegaard MLS, Goetze JP, Damm P, Mathiesen ER, Nielsen LB. Increased pro-Btype natriuretic peptide in infants of women with type I diabetes. Clin Chem 2005;51: 2296-302.

(9.) Dessi-Fulgheri P, Sarzani R, Rapelli A. Role of the natriuretic peptide in lipogenesis/lipolysis. Nutr Metab Cardiovasc Dis 2003;13:244-9.

(10.) Williams MJ, Hunter GR, Kekes-Szabo T, Nicholson C, Berland L. Intra-abdominal adipose tissue cut-points related to elevated cardiovascular risk in women. Int J Obes Relat Metab Disord 1996;20:613-7.

(11.) Sengenes C, Berlan M, De Glisezinski I, Lafontan M, Galitzky J. Natriuretic peptides: a new lipolytic pathway in human adipocytes. FASEB 2000;14:1345-51.

(12.) Vanderheyden M, Bartunek J, Goethals M. Brain and other natriuretic peptides: molecular aspects. Eur J Heart Fail 2004;6:261-8.

DOI: 10.1373/clinchem.2006.067736

Alexis E. Malavazos [1]

Lelio Morricone [1]

Alessandro Marocchi [2]

Federica Ermetici [1]

Bruno Ambrosi [1]

Massimiliano M. Corsi [3] *

[1] Endocrinology Unit

Department of Medical and

Surgical Sciences

University of Milan

Milan, Italy

[2] Institute of General Pathology

Laboratory of Clinical Pathology

University of Milan

Milan, Italy

[3] Policlinico San Donato IRCE

San Donato Milanese Italy

Department of Laboratory Medicine

Niguarda Ca' Granda Hospital

Milan, Italy

* Address correspondence to this author at: Institute of General Pathology, Laboratory of Clinical Pathology, University of Milan, Via L. Mangiagalli 31, Milan, I-20133, Italy. Fax 39-02-5031-5338; e-mail mmcorsi@unimi.it.
Table 1. Linear regression analysis of log-transformed NT pro-BNP
concentrations vs echocardiographic characteristics.

Echocardiographic characteristic P [r.sup.2]

LVMh x [m.sup.2.7], g/[m.sup.2.7] <0.0001 0.73
LVM, g <0.0001 0.50
End-diastolic posterior wall, cm <0.001 0.42
End-diastolic septum thickness, cm <0.001 0.43
Relative wall thickness, cm <0.01 0.32
Myocardial performance index <0.001 0.44
Early diastolic filling wave velocity, m/s <0.01 0.31

(a) LVMh x [m.sup.2.7], left ventricular mass indexed for height.
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Title Annotation:Letters
Author:Malavazos, Alexis E.; Morricone, Lelio; Marocchi, Alessandro; Ermetici, Federica; Ambrosi, Bruno; Co
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:Jun 1, 2006
Words:1419
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