Even mild changes in free thyroxine could influence the degree of heart failure measured by its biological surrogates

Both, severe hypo- or hyperthyroidism may alter hemodynamic parameters. The aim of our study was to ascertain, whether also distinct changes within normal range of free thyroxine (fT4) would be associated with an impairment of left ventricle function in patients with chronic heart failure. Hundred-forty-eight patients (m121, f27, mean age 63.8 +/- 1.14 years) with chronic heart failure, fT4 levels within the normal range (9-22 pmol/l) and without thyrostatics or substitution treatment. Degree of heart failure was quantified by plasma B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP). Patients with fT4 in the range 11.9-14.6 pmol/l [optimal, second-third quintile] had significantly lower NT-proBNP (718 +/- 70.4 pg/ml), than those with fT4 < or = 11.8 [low-normal, bottom quintile](1236 +/- 223.6 pg/ml; p<0.03) and those with fT4 over 14.6 pmol/l [high-normal, top two quintiles] (1192 +/- 114.9 pg/ml; p<0.0002). These differences remain significant, also if adjusted for age, gender and other confounders; adjusted odds ratio was 1.30 (1.05-1.59) for optimal vs. low-normal and 1.27 (1.04-1.55) for optimal vs. high-normal. Similar statistical differences were also found in BNP, but only when optimal and high-normal fT4 ranges were compared. In conclusion, the severity of heart failure seems to be also influenced by only mild deviations of fT4 concentrations from optimal levels.     

The clearance of BNP modeled using the NT-proBNP-BNP relationship

BACKGROUND: The ventricular myocardium simultaneously secretes two natriuretic peptides useful in the evaluation of heart failure: BNP, hormonally active, and NT-proBNP, the N-terminal end, non-hormonally active, but ultimately their concentrations differ and their clearance patterns are poorly defined. METHODS: We measured NT-proBNP and BNP in patients with and without heart failure and compared their concentrations using regression analysis. RESULTS: The relationship between NT-proBNP with BNP is nonlinear. Between 45 and 70 pmol of BNP/L (class II heart failure) the slope is much higher than in other ranges and the NT-proBNP/BNP ratio reaches its maximum in patients with class II NYHA heart failure. CONCLUSIONS: The difference in concentration for NT-proBNP and BNP can be related to the diffusion across the renal basement membrane. Their ratio is nonlinear because BNP is cleared faster than in patients with class II heart failure than other classes or normal, suggesting a change in a non-renal mode of clearance.     

Head-to-head comparison of BNP and IL-6 as markers of clinical and experimental heart failure: Superiority of BNP

Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P<0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P<0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P<0.01 vs. CTRL) and LV dysfunction (EF<45%, both P<0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P<0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P<0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P<0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P<0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.     

Intérêt du dosage des peptides natriurétiques en urgence dans la dyspnée aiguë

Acute dyspnea often leads to an emergency room visit. B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are natriuretic peptide factors secreted by ventricular myocytes when pressure is exerted on the ventricular wall. BNP fights against the activation of the renin-angiotensin-aldosterone system, while NT-proBNP exhibits no activity in this regard. Elevated blood levels of these factors correlate with a variety of functional indices for left-sided heart failure. Several studies have demonstrated their usefulness as markers of left-sided heart failure, the main cause of acute dyspnea seen in emergency rooms. The diagnostic performance of BNP and NT-proBNP appears to be identical; it is, however, greater than that of the emergency room physician. BNP and NT-proBNP have high sensitivity and specificity in the diagnosis of acute heart failure. Briefly, when BNP is less than 100 pg/ml, heart failure is very unlikely (NT-proBNP <500 pg/ml); when it is greater than 400 pg/ml (NT-proBNP >2000 pg/ml); when it is greater than 400 pg/ml (NT-proBNP >2000 pg/ml), it is very likely. The early measurement of BNP in emergency room situations improves the care of patients presenting with acute dyspnea and makes it possible to reduce hospitalisation costs.     

Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

OBJECTIVE: We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes. METHODS: 22 GHD patients were investigated in a double-blind randomized study and 90 GHD patients in an open study at baseline and after 6 and 12 months of GH replacement therapy. RESULTS: In the placebo-controlled trial, the FT(3) levels increased after 6 months in the GH-treated group, and in the open study the FT(3) levels tended to increase. Other hormone concentrations did not change in either part of the study. Four patients required an increase in thyroxine dose, while 2 patients needed dose reduction. One originally euthyroid patient required thyroxine replacement. Two patients with originally conserved pituitary-adrenal function developed ACTH insufficiency. The hydrocortisone dose was increased in 1 and decreased in 1 of the 66 patients with secondary hypocortisolism. None of the females required any adjustment of sex hormone replacement therapy. Two of 37 males needed dose increase of testosterone, while 1 needed dose reduction. CONCLUSION: GH replacement therapy required dose adjustments regarding other hormone replacement therapies in 12.2% (n = 11), while initiation of new hormone replacement was performed in 3.3% (n = 3) of the 90 patients during the 1-year follow-up. Monitoring of pituitary hormone axes is advisable after commencement of GH replacement therapy, since changes of hormone replacement therapy was observed in a small but clinically significant number of patients.     

Plasma levels of total and active ghrelin in acromegaly and growth hormone deficiency

Ghrelin is an endogenous growth hormone (GH) secretagogue recently isolated from the stomach. Although it possesses a strong GH releasing activity in vitro and in vivo, its physiological significance in endogenous GH secretion remains unclear. The aim of this study was to characterize plasma ghrelin levels in acromegaly and growth hormone deficiency (GHD). We investigated plasma total and active ghrelin in 21 patients with acromegaly, 9 patients with GHD and 24 age-, sex- and BMI-matched controls. In all subjects, we further assessed the concentrations of leptin, soluble leptin receptor, insulin, IGF-I, free IGF-I and IGFBP-1, 2, 3 and 6. Patients with acromegaly and GHD as well as control subjects showed similar levels of total ghrelin (controls 2.004+/-0.18 ng/ml, acromegalics 1.755+/-0.16 ng/ml, p=0.31, GHD patients 1.704+/-0.17 ng/ml, p=0.35) and active ghrelin (controls 0.057+/-0.01 ng/ml, acromegalics 0.047+/-0.01 ng/ml, p=0.29, GHD patients 0.062+/-0.01 ng/ml, p=0.73). In acromegalic patients plasma total ghrelin values correlated negatively with IGF-I (p<0.05), in GHD patients active ghrelin correlated with IGF-I positively (p<0.05). In the control group, total ghrelin correlated positively with IGFBP-2 (p<0.05) and negatively with active ghrelin (p=0.05), BMI (p<0.05), WHR (p<0.05), insulin (p=0.01) and IGF-I (p=0.05). Plasma active ghrelin correlated positively with IGFBP-3 (p=0.005) but negatively with total ghrelin and free IGF-I (p=0.01). In conclusion, all groups of the tested subjects showed similar plasma levels of total and active ghrelin. In acromegaly and growth hormone deficiency plasma ghrelin does not seem to be significantly affected by changes in GH secretion.     

NT-proBNP and BNP values in cardiac patients with different degree of left ventricular systolic dysfunction

We investigated the performance of brain natriuretic peptides (BNP and NT-proBNP) in detecting various degrees of left ventricular systolic dysfunction. The NT-proBNP assay (Roche) and the BNP assay (Bayer Shionoria) were performed in 46 patients (mean age 50 years; range 20-79 years) with various types of heart disease (chronic heart failure due to coronary artery disease, cardiomyopathy, acquired valve disease, congenital heart diseases) and different impairment of left ventricular systolic dysfunction was assessed by echocardiography. Patients were divided into four groups according to the left ventricular ejection fraction (LVEF) correlated with clinical severity. Significant differences in medians of NT-proBNP and BNP values between all groups were determined (P= 0.0161 for NT-proBNP and P=0.0180 for BNP). For identifying patients with severe systolic dysfunction (LVEF<40%), receiver operating characteristic (ROC) analysis for both BNP and NT-proBNP was performed. The diagnostic performances expressed as areas under the curve were of 0.69 for NT-proBNP (cut off value 367 pg/ml) and 0.60 for BNP (cut off value 172 pg/ml). However, the BNP showed higher sensitivity (85 % vs. 63 %) and a higher positive predictive value (69 % vs 55 %) than the NT-proBNP. The negative predictive values of BNP and NT-proBNP were similar (70 % and 71 % respectively). Brain natriuretic peptides are promising markers for the diagnosis of severe left ventricular systolic dysfunction.     

Long-term efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension

Background. Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) is associated with a poor survival. Objectives. To evaluate the long-term response to a dual endothelin receptor antagonist in patients with inoperable CTEPH. Methods. All consecutive 18 patients (mean age 63±14 years) treated with bosentan for symptomatic inoperable CTEPH were included. Efficacy was evaluated by the log value of serum levels of N-terminal-pro brain natriuretic peptide (log NTpro BNP), New York Heart Association functional class (NYHA), and the six-minute walk test (6-MWT). All follow-up data (median 31 months) were compared with baseline and divided into: short-term (<12 months), mid-term (between 12 and 24 months), and long-term follow-up (>24 months). Results. At baseline, 15 patients were in NYHA class III and three in NYHA class IV, mean log NT-pro BNP level was 7.2±1.4 log pg/ml, and mean 6-MWT distance was 404±125 m. During short-term follow-up (n=18), the NYHA class improved (p=0.001), 6-MWT distance increased by 33 m (p=0.03), and log NT-pro BNP decreased to 6.9±1.4 log pg/ml (p=0.007). During mid-term follow-up (n=17), the NYHA class improved (p<0.001), the mean 6-MWT distance increased by 41 m (p=0.01), and log NT-pro BNP was 6.9±1.4 log pg/ml (p=0.31). During late followup (n=14) the NYHA class was still improved (p=0.03), the 6-MWT distance decreased by 9 m (p=0.73), and log NT-pro BNP was 7.1±1.5 log pg/ml (p=0.91). The overall four year survival rate was 88%. Conclusion: Bosentan seems to be effective during long-term treatment in patients with inoperable CTEPH. (Neth Heart J 2009;17:329–33).     

Leptin expression and leptin receptor gene polymorphisms in growth hormone deficiency patients

Growth hormone deficiency (GHD) patients have lower weight, height, bone age, insulin-like growth factor 1 (IGF-1) levels, GH levels, fat metabolism and skeletal growth. The association of leptin with GHD characteristics and the effect of gene variants of leptin on GHD are unknown. Our aim was to examine the association of circulating leptin levels and common genetic variants in leptin (LEP) and leptin receptor (LEPR) genes with anthropometric measures, circulating hormone concentrations and GHD. A case control study of 125 GHD cases and 159 control subjects were characterized for bone age, body mass index (BMI), height, weight, leptin, IGF-1, GH and their genotype at the leptin promoter G-2548A, and LEPR variants, K109R and Q223R, at Chung Shan Medical University Hospital. Leptin levels were significantly associated with lower bone age, weight and BMI in GHD patients. Leptin levels were also significantly associated with reduced IGF-1 levels in girls but not boys in both groups. The frequency of LEPR223 [A/G or A/A] genotype was significantly higher than the LEPR223 G/G genotype in the GHD group. The LEPR223 [A/G or A/A] genotype was significantly associated with increased weight and BMI in the control group, but not in the GHD group. In conclusion, the GHD group carried a significantly higher frequency of the LEPR [G/A or A/A] genotype and of the A allele (LEPR223R). The LEPR223R polymorphism affected weight and BMI in control, but not in GHD patients, suggesting that the effect of LEPR223 [A/G or A/A] genotype was counteracted by other factor(s) in GHD patients.     

Neurohormones and inflammatory mediators in patients with heart failure undergoing cardiac resynchronization therapy: time courses and prediction of response

Despite interest in neurohormonal activation as a determinant of prognosis in chronic heart failure (CHF) and as a target for pharmacological treatments, data are lacking on the time-related effects of electrical cardiac resynchronization therapy (CRT) on a broad spectrum of neurohormones and cytokines. The aim of this study was to assess time-courses and extents of changes within the neurohormonal profile of CHF patients treated with CRT. We performed a prospective follow-up study in 32 patients with NYHA class III-IV CHF to investigate the effects of CRT on a broad panel of neurohormones proposed for characterization of CHF patients. Levels of atrial and brain natriuretic peptides (ANP, BNP), epinephrine, norepinephrine, aldosterone, plasma renin activity, IL-6, TNF, soluble receptors sTNFR1 and 2, and chromogranin A were assessed before implantation and after 3 months of CRT; when feasible, measurements were also performed at 1 week, 1 month and 12 months (clinical evaluation, echocardiography and ECG were also performed at each time-point). The results showed that at 3 months improvement in NYHA class and echographically assessed left ventricular (LV) reverse structural remodeling were accompanied by significant reductions versus baseline in ANP and BNP, but not in other neurohormones. Moreover a baseline ANP concentration < or = 150 pg/ml was a good predictor of response to CRT in terms of NYHA class reduction and reverse LV remodeling. In conclusion 3 months of CRT significantly reduce natriuretic peptides concentrations, while values of other neurohormones and inflammatory cytokines are relatively unvaried. A baseline ANP concentration < or = 150 pg/ml might be a clinically useful predictor of medium-term response to CRT.     

Spontaneous nocturnal leptin secretion in children with myelomeningocele and growth hormone deficiency

OBJECTIVE: To examine the spontaneous leptin secretion in patients with myelomeningocele (MMC) and growth hormone deficiency (GHD). METHODS: Serum leptin levels were studied in 10 prepubertal MMC patients with GHD (CA 6.2 +/- 0.5 years), 10 patients with idiopathic GHD (IGHD; CA 7.6 +/- 0.7 years) and 12 children with normal variant short stature (NVSS; CA 7.6 +/- 0.5 years). Mean BMI (kg/m(2)) values of the groups did not differ significantly. Nocturnal leptin levels were analyzed over 10 h (blood samples every 20 min) and measured by specific radioimmunoassay. RESULTS: Mean leptin concentrations did not correlate with BMI in MMC patients. Nocturnal leptin secretion of MMC patients was significantly different to those of children with IGHD and NVSS. Morning leptin levels did not decline as observed in both other groups. CONCLUSION: Since all groups were matched for BMI values, we suggest a hypothalamic dysregulation of leptin secretion in MMC patients.     

扩张型心肌病慢性心力衰竭患者血浆脑利钠肽水平的临床意义

目的:探究扩张型心肌病慢性心力衰竭患者血浆脑利钠肽水平的临床意义。方法:收集2012年3月至2016年3月我院收治的90例扩张型心肌病慢性心力衰竭患者,将患者按照NYHA心功能分级分为A组(II级)20例、B组(III级)38例、C组(IV级)32例。比较各组患者的血浆脑力钠肽(BNP)以及超声心动图相关指标,包括左心室射血分数(LVEF)、左心房内径(LA)、左室舒张末期内径(LVEDD)以及左室收缩末期内径(LVESD),分析血浆BNP与NYHA分级和超声心动图相关指标的相关性,以及比较血浆BNP和LVEF在慢性心力衰竭病情程度中的能力。结果:C组患者的血浆BNP浓度显著高于A组和B组(P0.05),而B组患者的血浆BNP浓度显著高于A组,比较差异具有统计学意义(P0.05)。心脏超声检测发现,C组患者的LA显著高于A组(P0.05),而LVEF、LVEDD及LVESD比较差异无统计学意义(P0.05)。血浆BNP与NYHA分级呈正相关关系,但与LVEDD、LVESD、LVEF、LA无明显相关关系(P0.05)。血浆BNP对评价心力衰竭患者病情程度呈现出较强的能力(受试者工作特征曲线下面积=0.902,P0.001)。血浆BNP=523.5 pg/mL为中重度心力衰竭患者的诊断最佳值。LVEF对评价心力衰竭患者病情程度无明显能力(受试者工作特征曲线下面积=0.392,P=0.276)。结论:血浆BNP浓度对扩张型心肌病慢性心力衰竭患者的诊断、筛查以及心功能分级具有重要的临床意义。     

Demonstration of direct effects of growth hormone on neonatal cardiomyocytes

The cellular and molecular basis of growth hormone (GH) actions on the heart remain poorly defined, and it is unclear whether GH effects on the myocardium are direct or mediated at least in part via insulin-like growth factor (IGF-1). Here, we demonstrate that the cultured neonatal cardiomyocyte is not an appropriate model to study the effects of GH because of artifactual loss of GH receptors (GHRs). To circumvent this problem, rat neonatal cardiomyocytes were infected with a recombinant adenovirus expressing the murine GHR. Functional integrity of GHR was suggested by GH-induced activation of the cognate JAK2/STAT5, MAPK, and Akt intracellular pathways in the cells expressing GHR. Although exposure to GH resulted in a significant increase in the size of the cardiomyocyte and increased expression of c-fos, myosin light chain 2, and skeletal alpha-actin mRNAs, there were no significant changes in IGF-1 or atrial natriuretic factor mRNA levels in response to GH stimulation. In this model, GH increased incorporation of leucine, uptake of palmitic acid, and abundance of fatty acid transport protein mRNA. In contrast, GH decreased uptake of 2-deoxy-d-glucose and levels of Glut1 protein. Thus, in isolated rat neonatal cardiomyocytes expressing GHR, GH induces hypertrophy and causes alterations in cellular metabolic profile in the absence of demonstrable changes in IGF-1 mRNA, suggesting that these effects may be independent of IGF-1.     

Cardiac effects of low-dose growth hormone replacement therapy in growth hormone-deficient adults. An 18-month randomised,placebo-controlled,double-blind study

OBJECTIVE: To characterise the effect of long-term low-dose growth hormone (GH) treatment on cardiac anatomy and function. METHODS: 20 patients with multiple pituitary hormone deficiencies, including severe acquired GH deficiency (GHD), were randomly assigned to GH or placebo (P) for 18 months. Echocardiographic measurements were performed at baseline and after 6, 12 and 18 months. RESULTS: At baseline, 8 of 20 patients had diastolic dysfunction (6 severe and 2 borderline), while only 1 had systolic dysfunction. None of the investigated parameters of diastolic or systolic function changed during treatment. CONCLUSION: In adult onset GHD, diastolic dysfunction was present in 40% of the patients. None of the investigated values were different after 18 months of GH compared to placebo.     

Kidneys extract BNP and NT-proBNP in healthy young men.

Renal metabolism of the cardiac marker NH2-terminal-pro-brain natriuretic peptide (NT-proBNP) has been suggested. Therefore, we determined the renal extraction ratios of NT-proBNP and its bioactive coproduct brain natriuretic peptide (BNP) at rest and during exercise. In addition, the cerebral ratios were evaluated. Ten young healthy men were investigated at baseline, during moderate cycle exercise (heart rate: 140, Borg scale: 14-15), and in the recovery with BNP and NT-proBNP measured from the brachial artery and the jugular and renal veins, and the renal and cerebral extraction ratios (Ext-Ren and Ext-Cer, respectively) were calculated. Cardiac output, stroke volume, heart rate, mean arterial pressures, and estimated glomerular filtration were determined. BNP and NT-proBNP were extracted by the kidneys but not by the brain. We observed no effect of exercise. The mean values (+/- SE) of Ext-Ren of NT-proBNP were similar (0.19 +/- 0.05, 0.21 +/- 0.06, and 0.12 +/- 0.03, respectively) during the three sessions (P > 0.05). Also the Ext-Ren of BNP were similar (0.18 +/- 0.07, 0.15 +/- 0.11, and 0.14 +/- 0.06, respectively; P > 0.05). There were no significant differences between Ext-Ren of BNP and NT-proBNP during the three sessions (P > 0.05). The Ext-Cer of both peptides varied insignificantly between -0.21 +/- 0.15 and 0.11 +/- 0.08. The renal extraction ratio of both BNP and NT-proBNP is approximately 0.15-0.20. There is no cerebral extraction, and short-term moderate exercise does not affect these values. Our findings suggest that the kidneys extract BNP and NT-proBNP to a similar extent in healthy young men.     

MCL-1 (myosin light chains-1) in differential diagnosis of dyspnea

Myosin light chains-1 (MLC-1) have been recently associated with the markers of heart function (NYHA, LVEF, NT-proBNP). Verification of the relationship between markers of heart function (New York Heart Association classification (NYHA), left ventricle ejection fraction determination (LVEF), N terminal prohormone of natriuretic peptide B type BNP (NT-proBNP) and concentrations of myosin light chains-1 (MLC-1) was assessed. Patients examined for dyspnea without signs of acute coronary syndrome. All patients underwent echocardiography (calculation of left ventricle ejection fraction--LVEF) and in the serum of all subjects NT-proBNP (ELEIA) and MLC-1 (ELISA) were determined. In the 38 patients (21 men, 17 women), mean age of 58 years (+/-12 years as 1 SD), a significant negative correlation was found between NT-proBNP and LVEF (r = - 0.47; p = 0.02, Spearman). The median levels of NT pro-BNP were closely associated with NYHA classification (type II--584 ng/l, type III--2792 ng/l, type IV--6400 ng/l; p < 0.05). Individuals with clinical NYHA IV differed significantly in median MLC-1 concentrations from persons with clinical NYHA classification II and III (type II--5.7 ng/l, type III--8.9 ng/l, type IV--17 ng/l; p < 0.05). A significant negative correlation between MLC-1 and LVEF (-0.35; p < 0.03) and significant positive correlations between MLC-1 and NT-proBNP (0.42; p < 0.012) were found. In conclusion MLC-1 cannot be used as a diagnostic marker in differential diagnosis of dyspnea.     

Final height in children with idiopathic growth hormone deficiency treated with recombinant human growth hormone: the Belgian experience

BACKGROUND: The growth response to recombinant hGH (rhGH) treatment and final height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency (GHD) were studied. PATIENTS/METHODS: Two patient groups were compared: Group 1 with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5-0.7 IU/kg/week (0.17-0.23 mg/kg/week) from the mean +/- SD age of 11.9 +/- 3.1 years during 5.1 +/- 2.1 years. RESULTS: rhGH treatment induced a doubling of the height velocity during the first year and resulted in a normalisation of height in 53 (87%) patients. Final height was -0.7 +/- 1.1 SDS, being 170.4 +/- 7.2 cm in boys and 158.0 +/- 6.4 cm in girls. Corrected for mid-parental height, final height was 0.0 +/- 1.1 SDS. Ninety-two percent of the patients attained an adult height within the genetically determined target height range. Although height gain during puberty was smaller in the patients with induced puberty (boys: 17.1 +/- 7.0 cm vs. 27.5 +/- 6.6 cm (p < 0.005); girls: 9.6 +/- 7.4 cm vs. 22.2 +/- 6.1 cm (p < 0.005)), no differences in final height after adjustment for mid-parental height were found between patients with spontaneous or induced puberty. CONCLUSIONS: We conclude that patients with idiopathic GHD treated with rhGH administered as daily subcutaneous injections in a dose of 0.5-0.7 IU/kg/week reach their genetic growth potential, resulting in a normalisation of height in the majority of them, irrespective of spontaneous or induced puberty.     

Impact of glomerular filtration rate on urinary BNP and NT-proBNP levels in heart failure

B-type natriuretic peptide (BNP) and its inactive amino-terminal fragment (NT-proBNP) are diagnostic tools for heart failure (HF), but less is understood regarding the effects of renal function on their urinary concentrations. The objective was to analyze the influence of renal function, as estimated glomerular filtration rate (eGFR), on BNP and NT-proBNP concentrations in 90 HF outpatients (65 ± 12 years; 73% men), grouped according to eGFR below or above 60 mL/min. Patients with worse eGFR had higher serum NT-proBNP (p < 0.01) and BNP (p < 0.01) than patients with higher eGFR: NT-proBNP, but urinary levels did not reach statistical differences. In addition, a direct significant correlation between filtered load of serum NT-proBNP or BNP with their concentrations in urine was found in patients with eGFR above 60 mL/min (r = 0.66, p < 0.001 and r = 0.338, p < 0.05) and below 60 mL/min (r = 0.63, p < 0.001 and r = 0.406, p < 0.01). However, after normalizing urinary natriuretic peptide concentrations by their filtered load, we obtained a significant inverse and exponential relation in patients with worse renal function for NT-proBNP and BNP (r = -0.87, p = 0.001; and r = -0.71, p < 0.001, respectively) and in patients with eGFR>60 mL/min (r = -0.84, p < 0.001; and r = -0.72, p < 0.001, respectively). In conclusion, similar urinary NT-proBNP and BNP excretion was obtained in patients with high or low eGFR. Furthermore, despite the direct correlation between filtered load of serum natriuretic peptides with their urinary levels, an inverse an exponential relationship was obtained after normalizing urinary concentrations. Therefore, glomerular filtration does not seem to be the major determinant of both urinary peptide concentrations.     

N-terminal pro B-type natriuretic peptide levels predict newly detected atrial fibrillation in a population-based cohort

Background B-type natriuretic peptide (BNP) is secreted from cardiomyocytes and may reflect haemodynamic abnormalities predisposing to atrial fibrillation (AF). We aimed to investigate whether N-terminal pro BNP (NT-proBNP) is associated with newly detected AF in subjects obtained from the general population. Methods From the PREVEND programme (n=8592), we selected all subjects with an available baseline and four-year electrocardiogram and NTproBNP levels at baseline. We excluded subjects with AF at baseline and subjects with a serum creatinine >2.0 mg/dl. Results In total, 6494 subjects were eligible for the prospective analysis (aged 49±12 years, 49.7% men). At four years, AF was detected in 41 (0.6%) subjects. Median NT-proBNP levels at baseline in subjects with newly detected AF after four years was 62.2 (22.6 to 208.5) pg/ml as compared with 35.7 (15.9 to 68.7) pg/ml in those with sinus rhythm (p=0.001). Each 1 standard deviation increment in natural log transformed NT-proBNP was associated with a 54% (5% to 126%, p=0.028) increase in risk for AF after adjustment for other risk factors predisposing to AF. NT-proBNP levels above the sex-specific 80th percentile (97 pg/ml in women and 60 pg/ml in men) were associated with a multivariate odds ratio of 2.65 (1.22 to 5.76, p=0.01) for the occurrence of AF. Conclusion Plasma levels of NT-proBNP predict newly detected AF in subjects obtained from the general population independent of cardiovascular risk factors predisposing to AF. (Neth Heart J 2008;16:73-8.)