Skip Navigation

European Journal of Heart Failure 2006 8(5):468-476; doi:10.1016/j.ejheart.2005.10.018
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Muscari, A.
Right arrow Articles by Zoli, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Muscari, A.
Right arrow Articles by Zoli, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2005 European Society of Cardiology

Non-cardiac determinants of NT-proBNP levels in the elderly: Relevance of haematocrit and hepatic steatosis

Antonio Muscaria,*, Annalisa Berzigottia, Giampaolo Bianchia, Claudia Giannonia, Amedeo Ligabueb, Donatella Magalottia, Dario Sbanoa, Annalisa Zacchinib and Marco Zolia

a Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna, S. Orsola-Malpighi Hospital Via Albertoni, 15, 40138 Bologna, Italy
b Laboratory of the Azienda USL Bologna Bologna, Italy

* Corresponding author. Tel.: +39 051 6362280; fax: +39 051 6362210. Email Address: amuscari{at}med.unibo.it


   Abstract
Top
 Abstract
1. Introduction
 2. Subjects and methods
 3. Results
 4. Discussion
 References
 
Background: The levels of B-type natriuretic peptide (BNP), a marker of heart failure, are higher in women and anaemic subjects, and tend to be lower in obese people. These relationships are still largely unexplained and it is unclear whether they also apply to the N-terminal portion of BNP precursor (NT-proBNP).

Aims: This cross-sectional study was performed to assess general and abdominal obesity, sex and other variables as possible extra-cardiac determinants of NT-proBNP.

Methods and results: A random sample of 713 subjects aged 65–74 years resident of Pianoro (Northern Italy) underwent assessment of NT-proBNP, several haemato-chemical variables, body mass index (BMI), body fat estimation (through skinfold measurement), waist circumference, intra-abdominal thickness and possible presence of hepatic steatosis (by ultrasound examination). An echocardiogram was performed in a subset of 125 subjects. In multivariable analysis NT-proBNP was inversely associated with haematocrit (r=0.22, P<0.0001) and hepatic steatosis (r=0.13, P=0.0001), while no association was found with BMI and body fat estimation. NT-proBNP was higher in women, but this relationship disappeared when haematocrit was included in the multivariable model. The associations with haematocrit and hepatic steatosis were independent from echocardiographic measurements.

Conclusion: NT-proBNP is increased in subjects with low haematocrit, which explains the higher values in women. Although NT-proBNP is not affected by general adiposity, low levels of NT-proBNP are associated with hepatic steatosis.

Key Words: NT-proBNP • Haematocrit • Hepatic steatosis • Obesity • Body mass index • Sex

Received April 14, 2005; Revised July 14, 2005; Accepted October 31, 2005


   1. Introduction
Top
 Abstract
 1. Introduction
2. Subjects and methods
 3. Results
 4. Discussion
 References
 
In recent years the diagnosis of heart failure has benefited from the introduction of measurement of cardiac natriuretic peptides. These hormonal substances are mainly produced by the atrial and ventricular myocardium, and induce vasodilatation, as well as water and salt excretion. B-type natriuretic peptide, in particular, is mainly produced in the left ventricle. Its synthesis is enhanced when wall stress increases, or in the presence of myocardial ischaemia, so that it is used both as a marker of heart failure [1] and in the prognosis of acute coronary syndromes [2].

It has recently been demonstrated that in obese people, BNP levels are lower [3,4], possibly due to an increased number of clearance receptors in the adipose tissue. This phenomenon might have important pathophysiological implications, since a reduced natriuresis might contribute to the appearance of obesity-associated hypertension. On the other hand, the same phenomenon might partially impair the utilization of BNP as a marker of heart failure in obese subjects.

In addition, other extra-cardiac factors are known to be associated with higher BNP levels, such as age [5], female sex [5] and low haemoglobin [6-8], although the mechanisms underlying these relationships are still largely unknown.

The N-terminal portion of BNP precursor (NT-proBNP) is very stable [9,10] and is characterized by a longer half-life and higher concentrations than the mature hormone BNP [11]. Although it has increasingly been used as a marker of heart failure [12-15], few studies have specifically addressed its main determinants [16,17]. Moreover, clearance receptors are not involved in the elimination of this N-terminal fragment from the circulation [18], therefore unlike BNP, NT-proBNP may not decrease in the presence of obesity [19,20]. Thus, this study was performed to identify potential extra-cardiac determinants and confounders of NT-proBNP levels in a wide population sample. In particular, the associations with several measures of general and abdominal adiposity were assessed, and the possible explanations for the different concentrations in the two sexes are discussed.


   2. Subjects and methods
Top
 Abstract
 1. Introduction
 2. Subjects and methods
3. Results
 4. Discussion
 References
 
2.1. Subjects
The Pianoro Study started in November 2003, when a questionnaire was sent to all subjects aged ≥65 years (n=3255) living in the municipality of Pianoro, a town near Bologna (Northern Italy). The questionnaire (8 pages) was a compilation of several smaller questionnaires, which had been previously validated [21-23]. Completed questionnaires providing information on lifestyle, risk factors for atherosclerosis, previous cardiovascular diseases and drugs prescribed were returned by 2022 subjects (62%). These subjects were then asked to attend our clinic, to provide written informed consent and documentation concerning possible previous ischaemic events, and to undergo a physical examination, blood sampling, an ECG, and an abdominal ultrasound assessment. All those who had not participated after the first invitation were sent a second invitation letter. Overall, 1163 subjects underwent all the planned investigations (36% of those invited). In the near future other types of intervention are planned, mainly aimed at promoting physical activity in the elderly, with a longitudinal study to assess the effects of such interventions.

The present investigation only includes the subjects aged 65-74 years. Exclusion criteria were a previous documented diagnosis of heart failure (N=22) or missing data (N=49). Thus, 713 subjects, 360 women and 353 men, eventually participated in the study.

The Pianoro Study was assessed and approved by the joint University-Hospital Ethical Committee.

2.2. Obesity, steatosis and coronary risk assessment
Body mass index (BMI) is the ratio between weight in kilograms and the square of height in meters. The skinfolds (bicipital, tricipital, suprailiac and subscapular) were measured in millimeter using a caliper, and the average of 3 measurements was used. The inclusion of these 4 skinfold values in a formula [24] allowed the estimation of the total amount of body fat, expressed as a percentage of weight. Waist circumference in centimeter was measured in a standing position, at the umbilicus level.

The following variables were assessed by abdominal ultrasound. 1) Thickness in millimeter of abdominal subcutaneous fat, 5 cm over the umbilicus on the xipho-umbilical line (7.5 MHz transducer). 2) Intra-abdominal thickness (distance in millimeter between the internal edge of abdominal muscles and the anterior wall of the aorta, 3.5 MHz transducer, at the same level of subcutaneous thickness measurement). 3) Degree of hepatic steatosis, 5 MHz transducer: 0 = absent, 1 = mild (hyperechoic liver with fine, tightly packed echoes), and 2 = moderate/severe (as 1, plus posterior beam attenuation, sometimes with failure to demonstrate portal vein bifurcation and the diaphragm) [25]. When assessed as a dichotomous variable, steatosis was defined as the presence of a moderate/severe pattern.

Metabolic syndrome was defined according to the presence of at least 3 of 5 possible factors [26], i.e. blood glucose ≥6.11 mmol/l (110 mg/dl), triglycerides ≥1.70 mmol/l (150 mg/dl), HDL cholesterol <1.04 mmol/l (40 mg/dl) in men and 1.30 mmol/l (50 mg/dl) in women, blood pressure ≥130/85 mm Hg, and waist circumference ≥102 cm in men or 88 cm in women. The 10 year risk of ischaemic coronary events was estimated by the Framingham function [27] that takes into account sex, age, systolic blood pressure, total cholesterol, HDL cholesterol, smoking, diabetes and possible left ventricular hypertrophy, as assessed by ECG.

2.3. Blood sampling and measurements
Venous blood sampling was performed in the morning, after a 12 h fast. All measurements were performed in the same laboratory and on the day of sampling. Serum C3 complement (an acute phase reactant and an inflammatory cytokine) was measured by a nephelometric method (Behring kits, Behringwerke AG, Marburg, Germany). Serum NT-proBNP was measured by an ElectroChemiLuminescence ImmunoAssay (ECLIA, proBNP Elecsys, Roche Diagnostics GmbH, Mannheim, Germany). The linear range of detection of NT-proBNP was of 5-35,000 pg/ml. The coefficients of variation for intra- and inter-assay measurements of NT-proBNP were, respectively, 4% and 5% for "low" mean levels (210 pg/ml), and 6% and 7% for higher mean levels (4400 pg/ml).

2.4. Echocardiographic substudy
A two-dimensional echocardiogram was performed in a subset of 125 subjects (58 men and 67 women) without atrial fibrillation, ischaemic ECG changes or a history of coronary heart disease, to ascertain whether the relationship between NT-proBNP and its extra-cardiac covariates were independent from the main cardiac morphological and functional parameters.

2.5. Statistical analysis
Since some variables, including NT-proBNP, were not normally distributed, the univariate analysis was performed by non-parametric tests: Mann-Whitney's test for the comparison of 2 groups, Kruskal-Wallis' analysis of variance for the comparison of 3 or more groups, and Spearman's test (rho correlation coefficient) for simple correlations between pairs of variables. The differences between percentages were assessed by {chi}2 test. Multivariable analysis (multiple linear regression) was performed after natural logarithmic transformation of the variables with non-Gaussian distribution, and partial r correlation coefficients are shown. Two-tailed tests were used throughout. Tests were considered significant for P values <0.01 when the whole population was evaluated, and for P values <0.05 when the smaller subset of subjects who underwent echocardiography was assessed. The statistical analysis was performed with BMDP software (SOLO, v. 4.0).


   3. Results
Top
 Abstract
 1. Introduction
 2. Subjects and methods
 3. Results
4. Discussion
 References
 
Table 1 reports the characteristics of the population studied, by sex. Most subjects were overweight or obese, and two thirds were hypertensive. The medications most frequently prescribed were ACE-inhibitors (41%), calcium antagonists (23%), diuretics (21%), beta-blockers (19%), statins (19%) and antiplatelet drugs (14%).


View this table:
[in this window]
[in a new window]

  		Table 1 Characteristics of the study population

 
NT-proBNP has a log-normal asymmetric distribution (Fig. 1), as indicated by the wider than the mean standard deviation (200.7±412.0 pg/ml). The median was 119 pg/ml, with 67-201 as interquartile range and 6-7283 as absolute range.


Figure 1
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Frequency distribution of NT-proBNP in the study population (the 6 highest outliers are not shown).

 
3.1. Association of NT-proBNP with discontinuous variables
NT-proBNP was higher in women than in men and in the presence of hypertension, but no relationships were detected with BMI class, metabolic syndrome, diabetes and smoking status (Table 2).


View this table:
[in this window]
[in a new window]

  		Table 2 Median NT-proBNP values according to the discontinuous variables

 
In the presence of hepatic steatosis the serum levels of NT-proBNP were lower. In particular, there was a progressive decrease in median NT-proBNP levels with an increasing degree of steatosis: 130 pg/ml, N=371 (no steatosis); 119 pg/ml, N=195 (mild steatosis); and 91 pg/ml, N=147 (moderate/severe steatosis) (P<0.001). The same result was obtained when the 119 subjects who drank more than 2 drinks per day were excluded from the analysis. Fig. 2 shows median NT-proBNP levels stratified according to BMI class and degree of steatosis. An inverse relationship with the degree of steatosis was present even in subjects with normal or low BMI, while NT-proBNP levels were highest in the subjects without steatosis, independent of BMI class. Considering different limit values for NT-proBNP, the best separation (maximum {chi}2 value) between subjects with and without moderate/severe steatosis corresponded to the limit of 80 pg/ml: 66 (29%) of the 225 subjects with NT-proBNP <80 pg/ml had steatosis, vs. 81 (17%) of the 488 subjects with a value greater than the same limit ({chi}2=15.3; P=0.0001).


Figure 2
View larger version (39K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Stratification of median NT-proBNP levels (pg/ml) according to the degree of hepatic steatosis and BMI class.

 
NT-proBNP was higher in the subjects with previous coronary or peripheral ischaemic events, coronary revascularization and ischaemic ECG changes, and in those taking antihypertensive drugs and statins. Finally, there was a strong association of NT-proBNP with atrial fibrillation and, to a lesser extent, with left bundle branch block.

The discontinuous variables significantly associated with NT-proBNP in univariate analysis were simultaneously related to the logarithm of NT-proBNP by multiple linear regression. According to this analysis, only the associations with the following 8 dichotomous variables, in decreasing order of significance, were confirmed: atrial fibrillation, hepatic steatosis, sex, hypertension, coronary revascularization, previous myocardial infarction, left bundle branch block, and ischaemic ECG changes.

3.2. Association of NT-proBNP with continuous variables
Table 3 reports the rho correlation coefficients of NT-proBNP with a series of continuous variables. NT-proBNP correlated directly with age, smoking and ESR, and inversely with heart rate, C3 complement, alanine aminotransferase, total cholesterol, triglycerides, blood glucose, intra-abdominal thickness, erythrocyte count, haemoglobin and haematocrit. There were no significant correlations with creatinine, BMI, body fat estimation, waist circumference and subcutaneous thickness. Moreover, of the above continuous variables univariately associated with NT-proBNP, only haematocrit, age and total cholesterol remained independently associated with the logarithm of NT-proBNP in multivariable analysis. Fig. 3 shows the regression line between haematocrit and logarithm of NT-proBNP: log(NT-proBNP)=7.234–0.059xHct; r=0.24; P<0.0001. The correlation remained significant when men and women were assessed separately: r=0.23, P<0.0001 and r=0.20, P=0.0002, respectively.


View this table:
[in this window]
[in a new window]

  		Table 3 Simple correlations of NT-proBNP with continuous variables

 


Figure 3
View larger version (20K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Linear regression of haematocrit with log (NT-proBNP). Filled circles represent males, unfilled squares females.

 
3.3. Final multivariable models
Several multivariable models were examined to simultaneously relate the 8 dichotomous and the 3 continuous variables identified in the previous analyses, plus BMI, to the logarithm of NT-proBNP (Table 4). After addition of haematocrit to the basal model, the relationship with sex was no longer confirmed. By a backward elimination procedure a conclusive model was obtained which included only variables associated with the logarithm of NT-proBNP with P values <0.01. In decreasing order of significance, these were atrial fibrillation, haematocrit (inverse relationship), age, hypertension, hepatic steatosis (inverse relationship), previous myocardial infarction, coronary revascularization, left bundle branch block, and ischaemic ECG changes. This model could explain 30% of NT-proBNP variability. When the same elimination procedure was separately repeated for men and women, the independent association of NT-proBNP with haematocrit was confirmed in both sexes, while the association with hepatic steatosis was confirmed in men only.


View this table:
[in this window]
[in a new window]

  		Table 4 Covariates of log (NT-proBNP): multiple linear regression analysis

 
3.4. Substudy with adjustment for echocardiographic parameters
In a subgroup of 125 subjects an echocardiogram was performed, and both haematocrit and hepatic steatosis remained significantly associated with the logarithm of NT-proBNP (respectively, r=0.21 and r=0.19, P=0.03) after adjustment for age, sex, BMI, left ventricular ejection fraction and the following parameters referred to body surface: left atrial diameter, end-diastolic left ventricular volume, left ventricular mass and right ventricular diameter.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Subjects and methods
 3. Results
 4. Discussion
References
 
4.1. NT-proBNP, haematocrit and female sex
This study has shown a continuous and progressive inverse relationship of the logarithm of NT-proBNP with haematocrit, which is stronger, in multivariable analysis, than the relationship with haemoglobin (the relationship with haemoglobin had already been found for BNP [6-8], but it had not been adjusted for haematocrit). Most laboratories take into account the repeated findings of higher BNP and NT-proBNP values in women than in men [5,16,17], and often propose different normal values for the two sexes. So far, the reason for such a difference has been unknown. However, the addition of haematocrit to our multivariable model caused the disappearance of the relationship of NT-proBNP with female sex. This is understandable considering the fact that women have lower haematocrit values than men. Thus, the association of NT-proBNP with female sex seems to be entirely explainable on the basis of the association of NT-proBNP with haematocrit. A confirmation that the primary relationship is with haematocrit, and not with sex, also comes from the fact that NT-proBNP and haematocrit are significantly associated in each of the two sexes.

In the presence of a low haematocrit the circulation becomes hyperkinetic, which might be a cause of ventricular wall stress. Indeed in women, as confirmed by this study, average heart rate is higher than in men. However, it has been demonstrated that an increase in heart rate is associated with reduced levels of BNP [17]. On the other hand, a low haematocrit might simply reflect plasma volume expansion, with stretching of the ventricular walls. However, this study has shown that the relationship between haematocrit and NT-proBNP is independent from the main echocardiographic volume and mass indexes of the cardiac chambers, and the same conclusion was reached when the relationship between haemoglobin and BNP was assessed in a Japanese population [6]. Overall, these data may have important pathophysiological implications, suggesting that a low haematocrit may represent a direct stimulus to BNP production, through mechanisms and receptors that are presently unknown, within a homeostatic process of haemodilution control. In turn, the subsequent increase in BNP would tend to bring haematocrit towards normality, as suggested by the increase in haematocrit observed following BNP infusion in animal models [28].

4.2. NT-proBNP, BMI and hepatic steatosis
A strong inverse relationship between BMI and BNP has previously been demonstrated by others [3,4]. However, this study has clearly shown that there is no significant relationship, either univariate or multivariate, between indices of general adiposity, such as BMI and body fat estimation, and NT-proBNP levels, thus supporting our original hypothesis.

This study has also shown that the subjects with increased intra-abdominal thickness, and especially those with hepatic steatosis, have lower levels of NT-proBNP. Although hepatic production of ANP and CNP has been demonstrated [29], it seems that synthesis of BNP does not occur in the liver [29], so that hepatic damage cannot be a direct cause of reduced serum levels of NT-proBNP. Indeed liver cirrhosis, a relevant cause of hepatic damage, is associated with increased (not reduced) BNP and proBNP levels [30].

On the other hand, in the last few years it has been reported that natriuretic peptides exert an important lipolytic action in the adipose tissue, interacting with specific receptors and activating a cGMP dependent pathway [31,32]. It is therefore tempting to consider the speculative hypothesis that in subjects with a primary reduced basal production of BNP, in addition to salt retention, an accumulation of triglycerides in the adipose tissue may take place, which would specifically occur at the abdominal level. And indeed, in the presence of genetically induced variations in natriuretic peptides, an increased susceptibility to abdominal adiposity has been demonstrated [33]. Abdominal obesity is the recognized cause of a relevant proportion of cases of non-alcoholic fatty liver disease [34]. Thus, hepatic steatosis might be regarded as a marker of augmented deep visceral fat, a marker that might be even more sensitive than the usual direct measurements, such as waist circumference or intra-abdominal thickness. Why there may be a subgroup of people with inappropriately low basal BNP production is presently unknown. Such a subgroup might be the result of some form of evolutionary advantage, or might simply correspond to the left tail of the log-normal BNP distribution. However, the implications of these concepts, if confirmed by prospective and interventional studies, would be relevant, as a relative deficiency in BNP could be involved in a potentially modifiable mechanism contributing to the appearance of visceral obesity, with possible ensuing insulin resistance and metabolic syndrome.

4.3. Other main findings
In agreement with other studies [35], NT-proBNP was strongly associated with atrial fibrillation. In our 10 subjects with atrial fibrillation, NT-proBNP ranged from 541 to 5560 pg/ml. From these data it seems that NT-proBNP would be a poor marker of heart failure in the presence of atrial fibrillation. Although the studied sample consisted of an elderly population within a narrow age range, the correlation between age and NT-proBNP was still one of the strongest. On the other hand, it is indeed the narrow age range and the absence of subjects with present or previous heart failure, associated with a restricted range of renal function, that might have weakened the known direct relationship between NT-proBNP and serum creatinine [16]. The increase in NT-proBNP in the presence of left bundle branch block seems to be an almost novel finding (it has only been reported in patients with coronary syndrome X [36]), but it is however compatible with the known dependence of NT-proBNP peptide from ventricular wall stress. Moreover, the associations with coronary revascularization and ischaemic ECG changes are in agreement with the results of previous studies showing a link with myocardial ischaemia [2].

4.4. Limitations
We recognize the following main limitations of our study: 1) its cross-sectional design allows the detection of associations, but not the demonstration of cause-effect relationships; 2) the sample age range was narrow, so that our conclusions might not be applicable to the general population; 3) the mature hormone BNP was not measured; 4) a CT or MR abdominal scanning, which could provide a more sensitive assessment of visceral fat, was not performed and 5) the echocardiograms were not executed in the whole sample, but in a selected subgroup of subjects.

4.5. Conclusions
This population study has shown that levels of NT-proBNP are increased in the presence of a low haematocrit, an association that explains the higher values in women. Unlike the mature hormone BNP [3,4], NT-proBNP is not affected by general obesity. However, low levels of NT-proBNP are associated with hepatic steatosis and increased intra-abdominal thickness, two different markers of visceral adiposity.


   Acknowledgements
 
The study was supported by grants from Fondazione Cassa di Risparmio in Bologna, and Regione Emilia Romagna-Piani per la Salute.


   References
Top
 Abstract
 1. Introduction
 2. Subjects and methods
 3. Results
 4. Discussion
 References
 

  1. Cowie M.R., Mendez G.F. BNP and congestive heart failure. Prog Cardiovasc Dis (2002) 44:293–321.[CrossRef][Web of Science][Medline]
  2. Galvani M., Ferrini D., Ottani F. Natriuretic peptides for risk stratification of patients with acute coronary syndromes. Eur Heart J (2004) 6:327–333.[CrossRef]
  3. Wang T.J., Larson M.G., Levy D., et al. Impact of obesity on plasma natriuretic peptide levels. Circulation (2004) 109:594–600.[Abstract/Free Full Text]
  4. Mehra M.R., Uber P.A., Park M.H., et al. Obesity and suppressed B-type natriuretic peptide levels in heart failure. J Am Coll Cardiol (2004) 43:1590–1595.[Abstract/Free Full Text]
  5. Redfield M.M., Rodeheffer R.J., Jacobsen S.J., Mahoney D.W., Bailey K.R., Burnett J.C. Jr. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol (2002) 40:976–982.[Abstract/Free Full Text]
  6. Tsuji H., Nishino N., Kimura Y., et al. Haemoglobin level influences plasma brain natriuretic peptide concentration. Acta Cardiol (2004) 59:527–531.[CrossRef][Web of Science][Medline]
  7. Kanda H., Kita Y., Okamura T., et al. What factors are associated with high plasma B-type natriuretic peptide levels in a general Japanese population? J Hum Hypertens (2005) 19:165–172.[CrossRef][Web of Science][Medline]
  8. Knudsen C.W., Clopton P., Westheim A., et al. Predictors of elevated B-type natriuretic peptide concentrations in dyspneic patients without heart failure: an analysis from the breathing not properly multinational study. Ann Emerg Med (2005) 45:573–580.[CrossRef][Web of Science][Medline]
  9. Barnes S.C., Collinson P.O., Galasko G., Lahiri A., Senior R. Evaluation of N-terminal pro-B type natriuretic peptide analysis on the elecsys 1010 and 2010 analysers. Ann Clin Biochem (2004) 41:459–463.[Abstract/Free Full Text]
  10. Mueller T., Gegenhuber A., Dieplinger B., Poelz W., Haltmayer M. Long-term stability of endogenous B-type natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) in frozen plasma samples. Clin Chem Lab Med (2004) 42:942–944.[CrossRef][Web of Science][Medline]
  11. Pemberton C.J., Johnson M.L., Yandle T.G., Espiner E.A. Deconvolution analysis of cardiac natriuretic peptides during acute volume overload. Hypertension (2000) 36:355–359.[Abstract/Free Full Text]
  12. Hunt P.J., Yandle T.G., Nicholls M.G., Richards A.M., Espiner E.A. The amino-terminal portion of pro-brain natriuretic peptide (Pro-BNP) circulates in human plasma. Biochem Biophys Res Commun (1995) 214:1175–1183.[CrossRef][Web of Science][Medline]
  13. Hunt P.J., Richards A.M., Nicholls M.G., Yandle T.G., Doughty R.N., Espiner E.A. Immunoreactive amino-terminal pro-brain natriuretic peptide (NT-PROBNP): a new marker of cardiac impairment. Clin Endocrinol (1997) 47:287–296.[CrossRef][Medline]
  14. Richards A.M., Doughty R., Nicholls M.G., et al. Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand heart failure group. J Am Coll Cardiol (2001) 37:1781–1787.[Abstract/Free Full Text]
  15. Richards A.M., Nicholls M.G., Yandle T.G., et al. Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction. Circulation (1998) 97:1921–1929.[Abstract/Free Full Text]
  16. Raymond I., Groenning B.A., Hildebrandt P.R., et al. The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population. Heart (2003) 89:745–751.[Abstract/Free Full Text]
  17. Loke I., Squire I.B., Davies J.E., Ng L.L. Reference ranges for natriuretic peptides for diagnostic use are dependent on age, gender and heart rate. Eur J Heart Fail (2003) 5:599–606.[Abstract/Free Full Text]
  18. Magnusson M., Melander O., Israelsson B., Grubb A., Groop L., Jovinge S. Elevated plasma levels of Nt-proBNP in patients with type 2 diabetes without overt cardiovascular disease. Diabetes Care (2004) 27:1929–1935.[Abstract/Free Full Text]
  19. Schnabel R., Rupprecht H.J., Lackner K.J., et al. Analysis of N-terminal-pro-brain natriuretic peptide and C-reactive protein for risk stratification in stable and unstable coronary artery disease: results from the atherogene study. Eur Heart J (2005) 26:241–249.[Abstract/Free Full Text]
  20. Hermann-Arnhof K.M., Hanusch-Enserer U., Kaestenbauer T., 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) 2005:138–143.
  21. Muscari A., Massarelli G., Bastagli L., et al. Relationship of serum C3 to fasting insulin, risk factors and previous ischaemic events in middle-aged men. Eur Heart J (2000) 21:1081–1090.[Abstract/Free Full Text]
  22. Johnson J.A., Coons S.J., Ergo A., Szava-Kovats G. Valuation of EuroQOL (EQ-5D) health states in an adult US sample. Pharmacoeconomics (1998) 13:421–433.[CrossRef][Web of Science][Medline]
  23. Dinger M.K., Oman R.F., Taylor E.L., Vesely S.K., Able J. Stability and convergent validity of the physical activity scale for the elderly (PASE). J Sports Med Phys Fitness (2004) 44:186–192.[Web of Science][Medline]
  24. Durnin J.V., Womersley J. Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years. Br J Nutr (1974) 32:77–97.[CrossRef][Web of Science][Medline]
  25. Joseph A.E., Saverymuttu S.H., al-Sam S., Cook M.G., Maxwell J.D. Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol (1991) 43:26–31.[CrossRef][Web of Science][Medline]
  26. Expert panel on detection, evaluation and treatment of high blood cholesterol in adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA (2001) 285:2486–2497.[Free Full Text]
  27. Anderson K.M., Odell P.M., Wilson P.W.F., Kannel W.B. Cardiovascular disease risk profiles. Am Heart J (1990) 121:293–298.[CrossRef][Web of Science]
  28. Woods R.L., Jones M.J. Atrial, B-type, and C-type natriuretic peptides cause mesenteric vasoconstriction in conscious dogs. Am J Physiol (1999) 276:R1443–R1452.[Web of Science][Medline]
  29. Vollmar A.M., Paumgartner G., Gerbes A.L. Differential gene expression of the three natriuretic peptides and natriuretic peptide receptor subtypes in human liver. Gut (1997) 40:145–150.[Abstract/Free Full Text]
  30. Henriksen J.H., Gotze J.P., Fuglsang S., Christensen E., Bendtsen F., Moller S. Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease. Gut (2003) 52:1511–1517.[Abstract/Free Full Text]
  31. Sarzani R., Dessi-Fulgheri P., Paci V.M., Espinosa E., Rappelli A. Expression of natriuretic peptide receptors in human adipose and other tissues. J Endocrinol Invest (1996) 19:581–585.[Web of Science][Medline]
  32. Sengenes C., Berlan M., De Glisezinski I., Lafontan M., Galitzky J. Natriuretic peptides: a new lipolytic pathway in human adipocytes. FASEB J (2000) 14:1345–1351.[Abstract/Free Full Text]
  33. Sarzani R., Strazzullo P., Salvi F., et al. Natriuretic peptide clearance receptor alleles and susceptibility to abdominal adiposity. Obes Res (2004) 12:351–356.[Web of Science][Medline]
  34. Sabir N., Sermez Y., Kazil S., Zencir M. Correlation of abdominal fat accumulation and liver steatosis: importance of ultrasonographic and anthropometric measurements. Eur J Ultrasound (2001) 14:121–128.[CrossRef][Medline]
  35. Silvet H., Young-Xu Y., Walleigh D., Ravid S. Brain natriuretic peptide is elevated in outpatients with atrial fibrillation. Am J Cardiol (2003) 92:1124–1127.[CrossRef][Web of Science][Medline]
  36. Dudek D., Rzeszutko L., Petkow Dimitrow P., et al. Circulating N-terminal brain natriuretic peptide precursor and endothelin levels in patients with syndrome X and left bundle branch block with preserved systolic function. Int J Cardiol (2001) 79:25–30.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 StrokeHome page
A. Muscari and M. Zoli
Albumin-Induced Hematocrit-Lowering and B-type Natriuretic Peptide Increase
Stroke, March 1, 2007; 38(3): 858 - 858.
[Full Text] [PDF]

Home page
 StrokeHome page
M. D. Ginsberg, M. D. Hill, and Y. Y. Palesch
Response to Letter by Muscari and Zoli
Stroke, March 1, 2007; 38(3): 859 - 859.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Muscari, A.
Right arrow Articles by Zoli, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Muscari, A.
Right arrow Articles by Zoli, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?