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Letters to the Editor |
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
aAddress 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{at}unimi.it.
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-Arnhof 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/m2 (median, 41.7 kg/m2); 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 (r2 = 0.60; P <0.0001) and VAT/SAT (r2 = 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 cm2) (10) had higher mean NT-proBNP concentrations than those with VAT <130 cm2 (n = 12) [mean (SD), 194.13 (14.6) vs 145.25 (10.7) ng/L; median 162 vs 138 ng/L; P <0.02].
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Senegenès 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 hormone-like 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 cm2 (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
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