The relationship between fetuin-A level and the clinical features of patients with coronary artery disease associated with iron deficiency
DOI:
https://doi.org/10.14739/2310-1237.2023.3.288735Keywords:
coronary artery disease, iron deficiency, anemia, fetuin-A, cardiac remodeling, autonomic dysfunction, riskAbstract
The aim of the study: to assess the relationship between the level of fetuin-A and features of clinical hemogram, ferrokinetic parameters, vegetative and structural-functional changes of the myocardium in patients with coronary artery disease (CAD) associated with different stages of iron deficiency (ID).
Materials and methods. The study involved 90 patients with CAD: stable angina pectoris II–III FC (35 men and 55 women, age – 69 (61; 72)). All patients were divided into 4 clinical groups depending on the parameters of iron metabolism and hemogram: I (n = 16) – patients with absolute ID, II (n = 15) – with latent ID, III (n = 14) – with functional ID; IV (n = 45) – patients CAD without iron metabolism disorders. The physiological concentration of fetuin-A was determined in 15 conditionally healthy people. The results of echocardioscopy, Holter ECG monitoring and their relationship with the level of fetuin-A were analyzed.
Results. In patients with CAD associated with various stages of ID, there is a decrease in the concentration of fetuin-A in direct proportion to the degree of progression of sideropenia was established. It was established that there is a relationship between the level of fetuin-A and the concentration of ferritin and transferrin saturation for patients with absolute ID as well as the number of erythrocytes in patients with functional ID. It was established that there is a relationship between the level of fetuin-A and PWd (rs = -0.60, p < 0.05) for patients with absolute ID; for patients with latent ID – with the E/A ratio (rs = +0.66, p < 0.05). In patients with absolute ID and latent ID a number of correlations between fetuin-A level and heart rate variability indicators in active and passive periods was established. The presence of a low level of fetuin-A in patients with CAD and ID increased the risk of left ventricular hypertrophy by 1.5 times, left ventricular diastolic dysfunction by 1.6 times, autonomic dysfunction by 2.14 times in the active period and 1.95 times in the passive period.
Conclusions. In patients with CAD, there is a progressive decrease in the fetuin-A level depending on the degree of ID, which contributes to the deepening of disorders of iron metabolism and clinical hemogram, negatively affects the structural and functional state of the myocardium and heart rate variability, increases the risk of developing myocardial hypertrophy, left ventricular diastolic dysfunction and vegetative imbalance.
References
- Chekol Abebe, E., Tilahun Muche, Z., Behaile T/Mariam, A., Mengie Ayele, T., Mekonnen Agidew, M., Teshome Azezew, M., Abebe Zewde, E., Asmamaw Dejenie, T., & Asmamaw Mengstie, M. (2022). The structure, biosynthesis, and biological roles of fetuin-A: A review. Frontiers in cell and developmental biology, 10, 945287. https://doi.org/10.3389/fcell.2022.945287
- Keçebaş, M., Güllülü, S., Sağ, S., Beşli, F., Açikgöz, E., Sarandöl, E., & Aydinlar, A. (2014). Serum fetuin-A levels in patients with systolic heart failure. Acta cardiologica, 69(4), 399-405. https://doi.org/10.1080/ac.69.4.3036656
- Lin, Y. H., Franc, V., & Heck, A. J. R. (2018). Similar Albeit Not the Same: In-Depth Analysis of Proteoforms of Human Serum, Bovine Serum, and Recombinant Human Fetuin. Journal of proteome research, 17(8), 2861-2869. https://doi.org/10.1021/acs.jproteome.8b00318
- Icer, M. A., & Yıldıran, H. (2021). Effects of fetuin-A with diverse functions and multiple mechanisms on human health. Clinical biochemistry, 88, 1-10. https://doi.org/10.1016/j.clinbiochem.2020.11.004
- Jahnen-Dechent, W., Heiss, A., Schäfer, C., & Ketteler, M. (2011). Fetuin-A regulation of calcified matrix metabolism. Circulation research, 108(12), 1494-1509. https://doi.org/10.1161/CIRCRESAHA.110.234260
- Jirak, P., Stechemesser, L., Moré, E., Franzen, M., Topf, A., Mirna, M., Paar, V., Pistulli, R., Kretzschmar, D., Wernly, B., Hoppe, U. C., Lichtenauer, M., & Salmhofer, H. (2019). Clinical implications of fetuin-A. Advances in clinical chemistry, 89, 79-130. https://doi.org/10.1016/bs.acc.2018.12.003
- Pagan, L. U., Gatto, M., Martinez, P. F., Okoshi, K., & Okoshi, M. P. (2022). Biomarkers in Cardiovascular Disease: The Role of Fetuin-A. Biomarcadores em Doenças Cardiovasculares: O Papel da Fetuína-A. Arquivos brasileiros de cardiologia, 118(1), 22-23. https://doi.org/10.36660/abc.20210980
- Carracedo, M., & Bäck, M. (2018). Fetuin-A in aortic stenosis and valve calcification: Not crystal clear. International journal of cardiology, 265, 77-78. https://doi.org/10.1016/j.ijcard.2018.04.115
- Chattopadhyay, M., Mukherjee, S., Chatterjee, S. K., Chattopadhyay, D., Das, S., Majumdar, S. S., Mukhopadhyay, S., Mukherjee, S., & Bhattarcharya, S. (2018). Impairment of energy sensors, SIRT1 and AMPK, in lipid induced inflamed adipocyte is regulated by Fetuin A. Cellular signalling, 42, 67-76. https://doi.org/10.1016/j.cellsig.2017.10.005
- Sardana, O., Goyal, R., Bedi, O. (2021). Molecular and pathobiological involvement of fetuin-A in the pathogenesis of NAFLD. Inflammopharmacology, 29(4), 1061-1074. https://doi.org/10.1007/s10787-021-00837-4
- Gerst, F., Wagner, R., Kaiser, G., Panse, M., Heni, M., Machann, J., Bongers, M. N., Sartorius, T., Sipos, B., Fend, F., Thiel, C., Nadalin, S., Königsrainer, A., Stefan, N., Fritsche, A., Häring, H. U., Ullrich, S., & Siegel-Axel, D. (2017). Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion. Diabetologia, 60(11), 2240-2251. https://doi.org/10.1007/s00125-017-4385-1
- Chattopadhyay, D., Das, S., Guria, S., Basu, S., & Mukherjee, S. (2021). Fetuin-A regulates adipose tissue macrophage content and activation in insulin resistant mice through MCP-1 and iNOS: involvement of IFNγ-JAK2-STAT1 pathway. The Biochemical journal, 478(22), 4027-4043. https://doi.org/10.1042/BCJ20210442
- Mukhuty, A., Fouzder, C., & Kundu, R. (2022). Fetuin-A excess expression amplifies lipid induced apoptosis and β-cell damage. Journal of cellular physiology, 237(1), 532-550. https://doi.org/10.1002/jcp.30499
- Das, S., Chattopadhyay, D., Chatterjee, S. K., Mondal, S. A., Majumdar, S. S., Mukhopadhyay, S., Saha, N., Velayutham, R., Bhattacharya, S., & Mukherjee, S. (2021). Increase in PPARγ inhibitory phosphorylation by Fetuin-A through the activation of Ras-MEK-ERK pathway causes insulin resistance. Biochimica et biophysica acta. Molecular basis of disease, 1867(4), 166050. https://doi.org/10.1016/j.bbadis.2020.166050
- Komsa-Penkova, R. S., Golemanov, G. M., Radionova, Z. V., Tonchev, P. T., Iliev, S. D., & Penkov, V. V. (2017). Fetuin-A – Alpha2-Heremans-Schmid Glycoprotein: From Structure to a Novel Marker of Chronic Diseases Part 1. Fetuin-A as a Calcium Chaperone and Inflammatory Marker. Journal of Biomedical and Clinical Research, 10(2), 90-97. https://doi.org/10.1515/jbcr-2017-0015
- Rudloff, S., Janot, M., Rodriguez, S., Dessalle, K., Jahnen-Dechent, W., & Huynh-Do, U. (2021). Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress. Nature communications, 12(1), 549. https://doi.org/10.1038/s41467-020-20832-7
- Ebrahim Ali, R. H., Zamzam, M. S. A., El Nouwairy, H. E. E. D., & Ashour, W. M. (2022). Fetuin A effect on iron status and hepcidin level in adenine induced chronic kidney disease male rat model. Zagazig University Medical Journal, 28(4), 839-847. URL: https://zumj.journals.ekb.eg/article_214488.html
- Stirnberg, M., Maurer, E., Arenz, K., Babler, A., Jahnen-Dechent, W., & Gütschow, M. (2015). Cell surface serine protease matriptase-2 suppresses fetuin-A/AHSG-mediated induction of hepcidin. Biological chemistry, 396(1), 81-93. https://doi.org/10.1515/hsz-2014-0120
- Wahedi, M., Wortham, A. M., Kleven, M. D., Zhao, N., Jue, S., Enns, C. A., & Zhang, A. S. (2017). Matriptase-2 suppresses hepcidin expression by cleaving multiple components of the hepcidin induction pathway. The Journal of biological chemistry, 292(44), 18354-18371. https://doi.org/10.1074/jbc.M117.801795
- Agarwal, A. K., & Yee, J. (2019). Hepcidin. Advances in chronic kidney disease, 26(4), 298-305. https://doi.org/10.1053/j.ackd.2019.04.005
- Nemeth, E., & Ganz, T. (2023). Hepcidin and iron in health and disease. Annual review of medicine, 74, 261-277. https://doi.org/10.1146/annurev-med-043021-032816
- Camaschella, C., Nai, A., & Silvestri, L. (2020). Iron metabolism and iron disorders revisited in the hepcidin era. Haematologica, 105(2), 260. https://doi.org/10.3324/haematol.2019.232124
- Weiss G., Ganz T., Goodnough L. T. (2021). Anemia of inflammation. Blood, 133(1), 40-50. https://doi.org/10.1182/blood-2018-06-856500
- Anker, S. D., Kirwan, B. A., van Veldhuisen, D. J., Filippatos, G., Comin-Colet, J., Ruschitzka, F., Lüscher, T. F., Arutyunov, G. P., Motro, M., Mori, C., Roubert, B., Pocock, S. J., & Ponikowski, P. (2018). Effects of ferric carboxymaltose on hospitalisations and mortality rates in iron-deficient heart failure patients: an individual patient data meta-analysis. European journal of heart failure, 20(1), 125-133. https://doi.org/10.1002/ejhf.823
- Snook, J., Bhala, N., Beales, I. L. P., Cannings, D., Kightley, C., Logan, R. P., Pritchard, D. M., Sidhu, R., Surgenor, S., Thomas, W., Verma, A. M., & Goddard, A. F. (2021). British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults. Gut, 70(11), 2030-2051. https://doi.org/10.1136/gutjnl-2021-325210
- Lazoryshynets, V. V., Kovalenko, V. M., Potashev, S. V., Fedkiv, S. V., Rudenko, A. V., Vitovskiy, R. M., Sychov, O. S., Rudenko, S. A., Ivaniv, Yu. A., Krikunov, O. A., Mazur, O. A., Hrubyak, L. M., Rusnak, A. O., Osovska, N. Yu., Deyak, S. I., Verich, N. M., & Beshlyaga, V. M. (2020). Ekhokardiohrafichne kilkisne otsiniuvannia kamer sertsia u doroslykh. Praktychni rekomendatsii Asotsiatsii sertsevo-sudynnykh khirurhiv Ukrainy ta Ukrainskoho tovarystva kardiolohiv [Cardiac chamber quantification by echocardiography in adults: Recommendations from the Association of cardiovascular surgeons of Ukraine and Ukrainian society of cardiology]. Ukrainskyi zhurnal sertsevo-sudynnoi khirurhii, 4(41), 96-117. [in Ukrainian]. https://doi.org/10.30702/ujcvs/20.4112/096-117.16.12.22020
- Faust, O., Hong, W., Loh, H. W., Xu, S., Tan, R. S., Chakraborty, S., Barua, P. D., Molinari, F., & Acharya, U. R. (2022). Heart rate variability for medical decision support systems: A review. Computers in biology and medicine, 145, 105407. https://doi.org/10.1016/j.compbiomed.2022.105407
- Sassi, R., Cerutti, S., Lombardi, F., Malik, M., Huikuri, H. V., Peng, C. K., Schmidt, G., & Yamamoto, Y. (2015). Advances in heart rate variability signal analysis: joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society. Europace, 17(9), 1341-1353. https://doi.org/10.1093/europace/euv015
- Shaffer, F., & Ginsberg, J. P. (2017). An Overview of Heart Rate Variability Metrics and Norms. Frontiers in public health, 5, 258. https://doi.org/10.3389/fpubh.2017.00258
- Konovalova, M. O., & Mykhailovska, N. S. (2023). Vzaiemozviazok ferokinetychnykh pokaznykiv zi stanom kardialnoho remodeliuvannia u khvorykh na ishemichnu khvorobu sertsia iz suputnim zalizodefitsytom [The relationship between ferrokinetic parameters and the state of cardiac remodeling in patients with coronary artery disease with concomitant iron deficiency]. Pathologia, 20(1), 20-26. [in Ukrainian]. https://doi.org/10.14739/2310-1237.2023.1.275370
- Lichtenauer, M., Wernly, B., Paar, V., Rohm, I., Jung, C., Yilmaz, A., Hoppe, U. C., Schulze, P. C., Kretzschmar, D., & Pistulli, R. (2018). Specifics of fetuin-A levels in distinct types of chronic heart failure. Journal of clinical laboratory analysis, 32(1), e22179. https://doi.org/10.1002/jcla.22179
- Göçer, K., Aykan, A. Ç., Kılınç, M., & Göçer, N. S. (2020). Association of serum FGF-23, klotho, fetuin-A, osteopontin, osteoprotegerin and hs-CRP levels with coronary artery disease. Scandinavian journal of clinical and laboratory investigation, 80(4), 277-281. https://doi.org/10.1080/00365513.2020.1728786
- Çakır, H., Kanat, S., Çakır, H., & Tenekecioğlu, E. (2022). Lower Serum Fetuin-A Levels are Associated with a Higher Ten-Year Mortality Risk in Patients with ST-Elevation Myocardial Infarction. Níveis mais Baixos de Fetuína-A Sérica estão Associados a um Maior Risco de Mortalidade em Dez Anos em Pacientes com Infarto do Miocárdio por Supradesnivelamento do Segmento ST. Arquivos brasileiros de cardiologia, 118(1), 14-21. https://doi.org/10.36660/abc.20201057
- Feistritzer, H. J., Klug, G., Reinstadler, S. J., Gröber, M. T., Mair, J., Kirchmair, R., Henninger, B., Franz, W. M., & Metzler, B. (2015). Fetuin-A is related to infarct size, left ventricular function and remodelling after acute STEMI. Open heart, 2(1), e000244. https://doi.org/10.1136/openhrt-2015-000244
- Albert, C. L., & Tang, W. (2018). Metabolic Biomarkers in Heart Failure. Heart Failure Clinics, 14(1), 109-118. https://doi.org/10.1016/j.hfc.2017.08.011
- Gan, Y., Zhao, M., & Feng, J. (2021). Association of fetuin-A levels and left ventricular diastolic dysfunction in patients on haemodialysis. International urology and nephrology, 53(8), 1689-1694. https://doi.org/10.1007/s11255-021-02796-9
- Zheng, J., Huang, M., Huang, Q., Chen, Q., & Chen, Z. (2021). The relationship between fetuin-A and coronary atherosclerotic heart disease (CHD) and CHD-related risk factors: A retrospective study. Medicine, 100(43), e27481. https://doi.org/10.1097/MD.0000000000027481
- Jirak, P., Stechemesser, L., Moré, E., Franzen, M., Topf, A., Mirna, M., Paar, V., Pistulli, R., Kretzschmar, D., Wernly, B., Hoppe, U. C., Lichtenauer, M., & Salmhofer, H. (2019). Clinical implications of fetuin-A. Advances in clinical chemistry, 89, 79-130. https://doi.org/10.1016/bs.acc.2018.12.003
- Pagan, L. U., Gatto, M., Martinez, P. F., Okoshi, K., & Okoshi, M. P. (2022). Biomarkers in Cardiovascular Disease: The Role of Fetuin-A. Biomarcadores em Doenças Cardiovasculares: O Papel da Fetuína-A. Arquivos brasileiros de cardiologia, 118(1), 22-23. https://doi.org/10.36660/abc.20210980
- Torres-Arellano, J. M., Echeverría, J. C., Ávila-Vanzzini, N., Springall, R., Toledo, A., Infante, O., Bojalil, R., Cossío-Aranda, J. E., Fajardo, E., & Lerma, C. (2021). Cardiac Autonomic Response to Active Standing in Calcific Aortic Valve Stenosis. Journal of clinical medicine, 10(9), 2004. https://doi.org/10.3390/jcm10092004
- Kryvenko, V. I., Kachan, I. S., Fedorova, O. P., Kolesnyk, M. Yu., Nepryadkina, I. V., Pachomova, S. P., Borodavko, O. I., & Borota, D. S. (2021). Kaltsynoz klapaniv sertsia: suchasnyi pohliad na problemu ta perspektyvy doslidzhen (ohliad literatury) [Heart valve calcinosis: a modern view on the problem and research prospects]. Praktykuiuchyi likar, (3), 15-21. [in Ukrainian]. Retrieved from: https://plr.com.ua/index.php/journal/article/view/651
- Brandon, L., Connolly, N., Hensey, M., O’Connor, S., Kenny, R., Maree, A., & Cruz-Gonzalez, I. (2023). Cardiovascular Autonomic Dysfunction and its association with Aortic Stenosis. Medical Research Archives, 11(1). https://doi.org/10.18103/mra.v11i1.3495
- Ng, H. Y., Hsueh, S. K., Lee, Y. T., Chiou, T. T., Huang, P. C., & Lee, C. T. (2017). Synergic Impact of Vascular Calcification and Low Autonomic Tone in Mortality of Hemodialysis Patients. Nephron, 137(2), 91-98. https://doi.org/10.1159/000477827
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