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Relationship between RANKL and neuroendocrine activation in elderly males with heart failure

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Abstract

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.

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Abbreviations

BMI:

Body mass index

CHF:

Congestive heart failure

LVEF:

Left ventricular ejection fraction

LVEDD:

Left ventricular end-diastolic diameter

NT-pro-BNP:

N-terminal pro-brain natriuretic peptide

NYHA:

New York Heart Association

sRANKL:

Serum RANKL levels

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Acknowledgments

This work was supported by Serbian Ministry of Science (grant 145019). We thank Merck Sharp and Dohme for their unrestricted educational grant. We also thank Mrs M. Argirovic from MSD for support during application procedure for educational grant. This work was also supported by biochemical laboratory “Zavod za laboratorijsku dijagnostiku Konzilijum’’—Belgrade, Serbia.

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Authors and Affiliations

  1. Cardiology Department, Clinical Medical Center Zvezdara, Belgrade, Serbia

    Goran Loncar, Sinisa Dimkovic & Natasa Markovic

  2. Institute for Medical Research, Military Medical Academy, Belgrade, Serbia

    Biljana Bozic

  3. Institute for Physiology and Biochemistry, University of Belgrade, Belgrade, Serbia

    Biljana Bozic

  4. Clinical Hospital Center Zemun, Belgrade, Serbia

    Vojkan Cvorovic & Biljana Putnikovic

  5. Institute for Statistics, Faculty of Organizational Sciences, University of Belgrade, Belgrade, Serbia

    Zoran Radojicic

  6. Clinic for Rheumatology and Clinical Immunology, Military Medical Academy, Belgrade, Serbia

    Nenad Prodanovic

  7. Clinic for Neurology, Military Medical Academy, Belgrade, Serbia

    Toplica Lepic

  8. Neuroendocrine Unit, Institute of Endocrinology, University Clinical Center of Serbia, Dr Subotic 13, 11000, Belgrade, Serbia

    Vera Popovic-Brkic

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  1. Goran Loncar
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Correspondence to Vera Popovic-Brkic.

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Loncar, G., Bozic, B., Cvorovic, V. et al. Relationship between RANKL and neuroendocrine activation in elderly males with heart failure. Endocr 37, 148–156 (2010). https://doi.org/10.1007/s12020-009-9282-z

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