Time filter

Source Type

Loncar G.,Clinical Medical Center Zvezdara | Fulster S.,Charite Medical School | Von Haehling S.,Charite Medical School | Von Haehling S.,Center for Cardiovascular Research | Popovic V.,University of Belgrade
International Journal of Cardiology | Year: 2013

Purpose of review: To review original research studies and reviews that present data on changes of body compartments and its mutual cross-talk with respect to the failing heart predominantly in non-cachectic patients with chronic heart failure (HF). Recent findings: Thanks to the integrative approach considering the whole organism, several recent studies suggested a complex network of communication between body compartments in respect to failing heart during the natural course of body wasting in non-cachectic patients with HF. Interestingly, recent studies suggest that failing heart trough secretion of natriuretic peptides acts on fat metabolism by inducing adiponectin secretion and lipolytic actions. Soluble myostatin released from the failing heart may induce skeletal muscle wasting in HF through an endocrine-like mechanism, as well. The likelihood that adipocyte-derived hormones influence bone status has been recently proven. Increased serum adiponectin was independently associated with reduced bone mass in elderly patients with non-cachectic HF. Summary: The concept of body compartments cross-talk in respect to failing heart provides a very interesting paradigm of integrative physiology. Better understanding of body compartments changes and its complex biochemical interplay may provide more efficacious and forehand treatment to prevent and/or postpone disability and improve quality of life in patients with chronic HF. © 2011 Elsevier Ireland Ltd.

Loncar G.,Clinical Medical Center Zvezdara
Journal of endocrinological investigation | Year: 2011

High PTH levels have been reported in patients with chronic heart failure (CHF). Similarly, its levels increase with aging and are related to impaired survival in elderly adults. However, its relationship with neuroendocrine activation and endothelial dysfunction in CHF has not been previously studied. Seventy-three CHF males with New York Heart Association (NYHA) classes II and III and 20 control subjects aged ≥ 55 yr were recruited. PTH, 25-hydroxyvitamin D [25(OH)D], N-terminal pro-brain natriuretic peptide (NT-pro-BNP), adiponectin, and osteoprotegerin were measured. Endothelial function (brachial flow mediated dilation), echocardiography, physical performance, and quality of life were assessed, as well. CHF patients had markedly increased serum PTH (77 ± 33 vs 40 ± 11 pg/ml, p<0.0001), NT-pro-BNP [1809 (2742) vs 67 (74) pg/ml, p<0.0001], adiponectin (17 ± 9 vs 10 ± 2 μg/ml, p<0.0001), osteoprotegerin, whereas 25(OH)D levels were decreased compared to controls. Increased PTH is positively correlated with NTpro- BNP (r=0.399, p<0.0001), adiponectin (r=0.398, p<0.0001), and osteoprotegerin, whereas negatively with 25(OH)D in CHF patients. Additionally, increased serum PTH was associated with endothelial dysfunction, echocardiographic variables of heart failure progression, impaired physical performance, and deteriorated quality of life. In a multivariate linear regression analysis, increased serum PTH was independently associated with neuroendocrine activation (NT-pro-BNP, adiponectin) and endothelial dysfunction in elderly CHF men (R2=0.455). Additionally, demonstrated relations with other well-established variables of heart failure severity suggest the potential role of serum PTH in the pathogenesis and non-invasive monitoring of heart failure progression. Future studies are needed to evaluate the predictive value of serum PTH for clinical outcomes as well as beneficial potential of PTH suppression in CHF patients.

Bozic B.,Military Medical Academy | Bozic B.,University of Belgrade | Loncar G.,Clinical Medical Center Zvezdara | Prodanovic N.,Military Medical Academy | And 4 more authors.
Journal of Cardiac Failure | Year: 2010

Background: The aim of the study was to investigate the associations of adiponectin and leptin to bone mass and bone specific surrogates in elderly males with chronic heart failure (CHF). Methods and Results: Seventy-three males (mean age 68 ± 7 years) with stable mild to moderate CHF and 20 healthy individuals age- and body mass index-matching underwent dual energy x-ray absorptiometry measurements (bone mineral density (BMD) at hip and lumbar spine, total bone mineral content, and body composition); echocardiography; 6-minute walk test; grip strength; and biochemical assessment including adiponectin, leptin, bone specific surrogates (osteocalcin, β-CrossLaps, osteoprotegerin [OPG], receptor activator of nuclear factor κB ligand [RANKL]), parathyroid hormone, 25-hydroxy vitamin D, testosterone, sex hormone-binding globulin, and NT-pro-BNP. Serum adiponectin, osteocalcin, β-CrossLaps, OPG, RANKL, and parathyroid hormone were significantly increased in CHF patients, whereas 25-hydroxy vitamin D was significantly lower compared to healthy controls. The significant positive association was found between adiponectin level with osteocalcin, β-CrossLaps, OPG, and RANKL among CHF patients. In multivariate regression analysis, adiponectin was a significant determinant of total hip BMD, although the variance was small (r 2 = 0.239), whereas leptin was determinant for total bone mineral content (r 2 = 0.469) in patients with CHF. Conclusions: Serum adiponectin is an independent predictor of BMD in elderly males with mild to moderate CHF, and showed a positive correlation to bone specific surrogates. Adiponectin, as cardioprotective hormone, seems to be able to exert a negative effect on bone mass in chronic heart failure. Further research is needed to confirm the potential for adipokines in the crosstalk between bone and energy metabolism in CHF patients. © 2010 Elsevier Inc. All rights reserved.

Bozic B.,Military Medical Academy | Bozic B.,University of Belgrade | Loncar G.,Clinical Medical Center Zvezdara | Prodanovic N.,Military Medical Academy | And 5 more authors.
Physiological Research | Year: 2011

Secondary hyperparathyroidism (SHPT) may contribute to the systemic illness that accompanies chronic heart failure (CHF). Healthy elderly with vitamin D deficiency who did not develop hyperparathyroidism (functional hypoparathyroidism, FHPT) had lower mortality than those who did. This study was designed to examine determinants of the PTH response in the vitamin D insufficient CHF patients. Sixty five vitamin D insufficient males with NYHA class II and III and 20 control subjects age ≥ 55 years were recruited. Echocardiography, physical performance, NT-pro-BNP, PTH, 25-hydroxyvitamin D (25(OH)D), adiponectin and bone activity surrogate markers (OPG, RANKL, OC, β-CTx) were assessed. Increased NYHA class was associated with SHPT, while physical performance was inferior compared to FHPT. SHPT was associated with lower left ventricular ejection fraction (LVEF) and flow mediated dilatation, but with higher left heart dimensions, left ventricular mass index and right ventricular systolic pressure. CHF patients with SHPT had increased NT-pro-BNP, adiponectin and bone markers, but decreased 25(OH)D compared to those with FHPT. Independent determinants for SHPT in CHF patients with vitamin D insufficiency were LVEF, adiponectin and β-CTx, irrespective of renal function and serum vitamin D levels. In conclusion, increased PTH levels, but not low vitamin D, demonstrated close relation to CHF severity.

Loncar G.,Clinical Medical Center Zvezdara | Bozic B.,Military Medical Academy | Bozic B.,University of Belgrade | Cvorovic V.,Clinical Hospital Center Zemun | And 7 more authors.
Endocrine | Year: 2010

The main cytokines regulating bone remodeling are the receptor activator of nuclear factor-κB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Recent data have linked RANKL and OPG to cardiovascular disease as well. NT-pro-BNP and adiponectin are well-established biomarkers of heart failure reflecting neuroendocrine activation in this multi-complex disorder. The objective of this article was to investigate whether RANKL is associated with neuroendocrine activation in 75 elderly males with mild to moderate congestive heart failure (CHF) and left ventricular ejection fraction <40%. The control group consisted of 20 healthy male volunteers with matching age and body mass index (BMI). Serum RANKL (sRANKL), OPG, NT-pro-BNP, adiponectin, leptin, clinical, and echocardiography parameters were evaluated. In comparison to the control group, the CHF patients showed significantly increased sRANKL levels [126.8 (122.6) vs. 47.8 (44.4) pg/ml, P < 0.0001]. There was a significant relative risk of systolic CHF in elderly males associated with increased sRANKL above the calculated cut-off of 83 pg/ml [OR = 10.286 (95%CI 3.079-34.356), P < 0.0001; RR = 3.600 (95%CI = 1.482-8.747)]. In the CHF patients, the log-transformed values of sRANKL levels correlated positively with the log-transformed values of the serum NT-pro-BNP and adiponectin levels (P = 0.004, r = 0.326 and P = 0.037, r = 0. 241, respectively), while inversely correlated with the BMI and creatinine clearance (P = 0.015, r = -0.281 and P = 0.042, r = -0.236, respectively). In multivariate regression model, sRANKL was a significant determinant of NT-pro-BNP independent of age, BMI and creatinine clearance (P = 0.002, R 2 = 0.546). In conclusion, our study suggests that in elderly males with systolic heart failure sRANKL was significantly associated with parameters of neuroendocrine activation such as NT-pro-BNP and adiponectin. Further studies are needed to elucidate the potential role of sRANKL in the complex pathogenesis of heart failure. © 2009 Humana Press.

Discover hidden collaborations