Correlation of Ceruloplasmin with Biomarkers of Cardiac Remodelling and Myofibrosis in Patients with Acute Decompensated Heart Failure Referred to a Tertiary Nurse Lead Heart Failure Clinic

Filip Málek^1,2*, Dagmar Vondráková^1,2, Oxana Komendová¹, Dana Říhová¹, Jana Vránová², Lenka Sedláčková³, Táňa Andreasová¹, Petr Neužil¹

¹Department of Cardiology, Na Homolce Hospital, Prague, Czech Republic.
²Third School of Medicine, Charles University, Prague, Czech Republic.
³Department of Clinical Biochemistry, Haematology and Immunology, Na Homolce Hospital, Prague, Czech Republic.

DOI: 10.4236/ojn.2015.511103                

Abstract

Background: Ceruloplasmin is an acute phase protein with plasma copper binding properties, and is a potent extracellular antioxidative enzyme. Inflammation and oxidative stress might explain the role of ceruloplasmin in the pathophysiology of heart failure. Study objective: The objective is to assess the correlation of ceruloplasmin levels with biomarkers of cardiac remodelling and myofibrosis in patients with acute decompensated heart failure. Patients and methods: Blood samples were taken and serum levels of soluble ST2, galectin-3, NT-proBNP and ceruloplasmin were analysed in 31 consecutive patients with systolic HF referred to tertiary care nurse lead heart failure clinic with acute decompensated CHF requiring i.v. diuretics. The mean patients’ age was 68 years, mean left ventricular ejection fraction (LV EF) was 29%, 66% patients had ischemic aetilogy of CHF and 33% had atrial fibrillation. Results: The mean ceruloplasmin level was 0.243 g/l, mean galectin-3 level was 1.26 ng/ml, mean sST2 level was 38.15 ng/ml, and mean NT-proBNP was 1927 pg/ml. The ceruloplasmin level correlated with NT-proBNP (r = 0.58, p < 0.05) and with sST2 (r = 0.77, p < 0.001), sST2 levels correlated significantly with NT-proBNP (r = 0.66, p < 0.01). The ceruloplasmin level did not correlate with galectin-3 concentration. Conclusion: The ceruloplasmin level correlates with the biomarkers of cardiac remodelling (NT-proBNP, sST2), but not with the biomarker of myofibrosis (galectin-3). This finding supports the hypothesis of inflammatory response in acute decompensated heart failure.

Keywords

Acute Decompensated Heart Failure, Ceruloplasmin, NT-proBNP, sST2, Galectin-3

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Mak, S. and Newton, G.E. (2001) The Oxidative Stress Hypothesis of Congestive Heart Failure. Chest, 120, 2035-2046.
[2]	Reunanen, A., Knekt, P. and Aaran, P.K. (1992) Serum Ceruloplasmin Level and the Risk of Myocardial Infarction and Stroke. American Journal of Epidemiology, 136, 1082-1090.
[3]	Mänttäri, M., Manninen, V., Huttunen, V.K., et al. (1994) Serum Ferritin and Ceruloplasmin as Coronary Risk Factors European Heart Journal, 15, 1599-1603.
[4]	Klipstein-Grobusch, K., Grobbee, D.E., Koster, F.E., et al. (1999) Serum Ceruloplasmin as a Coronary Risk Factor in the Elderly. The Rotterdam Study British Journal of Nutrition, 81, 139-144.
[5]	Ridker, P.M., Cushman, M., Stampfer, M.J., et al. (1997) Inflammation, Aspirin, and the Risk of Cardiovascular Disease in Apparently Healthy Men. New England Journal of Medicine, 336, 973-979. http://dx.doi.org/10.1056/NEJM199704033361401
[6]	Dadu, R.T., Dodge, R., Nambi, V., et al. (2013) Ceruloplasmin and Heart Failure in the Atherosclerosis Risk in Communities Study. Circ Heart Fail, 6, 936-943. http://dx.doi.org/10.1161/CIRCHEARTFAILURE.113.000270
[7]	Hammadah, M., Fan, Y., Wu, Y., et al. (2014) Prognostic Value of Elevated Serum Ceruloplasmin Levels in Patients with Heart Failure. Journal of Cardiac Failure, 20, 946-952.
[8]	Mueller, T., Dieplinger, B., Gegenhuber, A., et al. (2008) Increased Plasma Concentrations of Soluble ST2 Are Predictive for 1-Year Mortality in Patients with Acute Destabilized Heart Failure. Clinical Chemistry, 54, 752-756. http://dx.doi.org/10.1373/clinchem.2007.096560
[9]	Manzano-Fernández, S., Mueller, T., Pascual-Figal, D., et al. (2011) Usefulness of Soluble Concentrations of Interleukin family member ST2 as Predictor of Mortality in Patients with Acutely Decompensated Heart Failure Relative to Left Ventricular Ejection Fraction. The American Journal of Cardiology, 107, 259-267. http://dx.doi.org/10.1016/j.amjcard.2010.09.011
[10]	de Boer, R.A., Voors, A.A., Muntendam, P., et al. (2009) Galectin-3: A Novel Mediator of Heart Failure Development and Progression. European Journal of Heart Failure, 11, 811-817.
[11]	Shiva, S., Wang, X., Ringwood, L.A., et al. (2006) Ceruloplasmin Is a No Oxidase and Nitrite Synthase That Determines Endocrine No Homeostasis. Nature Chemical Biology, 2, 486-493. http://dx.doi.org/10.1038/nchembio813
[12]	Shukla, N., Maher, J., Masters, J., et al. (2006) Does Oxidative Stress Change Ceruloplasmin from a Protective to a Vasculopathic Factor? Atherosclerosis, 187, 238-250. http://dx.doi.org/10.1016/j.atherosclerosis.2005.11.035
[13]	Tang, W.H., Wu, Y., Hartiala, J., Hazen, S.L., et al. (2012) Clinical and Genetic Association of Serum Ceruloplasmin with Cardiovascular Risk. Arteriosclerosis, Thrombosis, and Vascular Biology, 32, 516-522. http://dx.doi.org/10.1161/ATVBAHA.111.237040
[14]	Engstrom, G., Hedblad, B., Tyden, P. and Lindgarde, F. (2009) Inflammation-Sensitive Plasma Proteins Are Associated with Increased Incidence of Heart Failure: A Population-Based Cohort Study. Atherosclerosis, 202, 617-622. http://dx.doi.org/10.1016/j.atherosclerosis.2008.05.038
[15]	Xu, Y., Lin, H., Zhou, Y., et al. (2013) Ceruloplasmin and the Extent of Heart Failure in Ischemic and Nonischemic Cardiomyopathy Patients. Mediators of Inflammation, 2013, Article ID: 348145. http://dx.doi.org/10.1155/2013/348145
[16]	Hendrichová, M., Málek, F., Koprivová, H., et al. (2010) Correlation of NT-proBNP with Metabolic Liver Function as Assessed with 13C-Methacetin Breath Test in Patients with Acute Decompensated Heart Failure. International Journal of Cardiology, 144, 321-322. http://dx.doi.org/10.1016/j.ijcard.2009.03.022
[17]	Sharma, U.C., Pokharel, S., van Brakel, T.J., et al. (2004) Galectin-3 Marks Activated Macrophages in Failure-Pronehy Pertrophied Hearts and Contributes to Cardiac Dysfunction. Circulation, 110, 3121-3128. http://dx.doi.org/10.1161/01.CIR.0000147181.65298.4D