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Associations of Whole Blood Zinc Levels with Coronary Artery Calcification and Future Cardiovascular Events in CKD Patients

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Abstract

This study was conducted to compare the differences of the whole blood zinc concentration in patients with chronic kidney disease (CKD) as compared to healthy controls, and to explore the correlations of the whole blood zinc level with coronary artery calcification (CAC) and cardiovascular event (CVE) in CKD patients. A total of 170 CKD patients and 62 healthy controls were recruited. The whole blood zinc concentration was determined in using atomic absorption spectroscopy (AAS) method. The degrees of CAC were evaluated by Agatston score based on computed tomography (CT). Regular follow-up visits were performed to record the incidence of CVE, and risk factors were analyzed by COX proportional hazard model and Kaplan–Meier survival curve. There were statistically significant lower zinc levels in CKD patients than in healthy population. The prevalence of CAC was 58.82% in CKD patients. Correlation analysis showed that dialysis duration, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), 25-hydroxyvitamin D3 (25(OH)D3), neutrophil–lymphocyte ratio (NLR), total cholesterol (TC), and high-sensitive C-reactive protein (Hs-CRP) were positively correlated with CAC, while albumin (ALB), hemoglobin (Hb), and zinc levels were negatively associated with CAC. Further COX proportional hazard model demonstrated that moderate to severe CAC, NLR, phosphate, 25(OH)D3, iPTH, and high-density lipoprotein (HDL) were associated with an increased risk for CVE, while zinc levels, Hb, and ALB were inversely associated with a reduced risk for CVE. Kaplan–Meier curve showed that low zinc (zinc < 86.62 μmol/L) patients and moderate to severe CAC patients had lower survival respectively. Our study found the lower levels of zinc and higher prevalence of CAC in CKD patients; the low zinc is involved in the high incidence rate of moderate to severe CAC and CVE in CKD patients.

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Data Availability

The data of this study are available from the corresponding author upon reasonable request.

References

  1. Agharazii M, St-Louis R, Gautier-Bastien A et al (2014) Inflammatory cytokines and reactive oxygen species as mediators of chronic kidney disease-related vascular calcification. Am J Hypertens 28(6):746–755

    Article  PubMed  Google Scholar 

  2. Banaszak M, Górna I, Przysławski J (2021) Zinc and the innovative Zinc-α2-glycoprotein adipokine play an important role in lipid metabolism: a critical review. 13(6):2023

  3. Bossola M, Di Stasio E, Viola A, et al (2020) Dietary daily sodium intake lower than 1500 mg is associated with inadequately low intake of calorie, protein, iron, zinc and vitamin B1 in patients on chronic hemodialysis. 12(1):260

  4. Chen J, Budoff MJ, Reilly MP et al (2017) Coronary artery calcification and risk of cardiovascular disease and death among patients with chronic kidney disease. JAMA Cardiol 2(6):635–643

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR et al (2013) Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet (London, England) 382(9889):339–352

    Article  PubMed  Google Scholar 

  6. Düsing P, Zietzer A, Goody PR et al (2021) Vascular pathologies in chronic kidney disease: pathophysiological mechanisms and novel therapeutic approaches. J Mol Med 99(3):335–348

    Article  PubMed  Google Scholar 

  7. King JCSDM, Woodhouse LR (2000) Zinc homeostasis in humans. J Nutr 130(5S Suppl):1360s-s1366

    Article  CAS  PubMed  Google Scholar 

  8. Vázquez-Lorente H, Dundjerović DM, Tatić SB et al (2022) Relationship between trace elements and matrix metalloproteinases 2 and 9 and their tissue inhibitors in medullary thyroid carcinoma. Biol Trace Elem Res

  9. Oner P, Er B, Orhan C, Sahin K (2023) Combination of phycocyanin, zinc, and selenium improves survival rate and inflammation in the lipopolysaccharide-galactosamine mouse model. Biol Trace Elem Res 201(3):1377–1387

    Article  CAS  PubMed  Google Scholar 

  10. Zhang TCX, Liu W, Li X, Wang F, Huang L, Liao S, Liu X, Zhang Y, Zhao Y (2017) Comparison of sodium, potassium, calcium, magnesium, zinc, copper and iron concentrations of elements in 24-h urine and spot urine in hypertensive patients with healthy renal function. J Trace Elem Med Biol 44(11):104–108

    Article  CAS  PubMed  Google Scholar 

  11. Krebs NF, Miller LV, Michael Hambidge K (2014) Zinc deficiency in infants and children: a review of its complex and synergistic interactions. Paediatr Int Child Health 34(4):279–288

    Article  PubMed  Google Scholar 

  12. Shimizu S, Tei R, Okamura M et al (2020) Prevalence of zinc deficiency in japanese patients on peritoneal dialysis: comparative study in patients on hemodialysis. 12(3):764

  13. Garagarza CVA, Caetano C, Ramos I, Sebastião J, Pinto M, Oliveira T, Ferreira A, Sousa Guerreiro C (2022) Zinc deficient intake in hemodialysis patients: a path to a high mortality risk. J Ren Nutr 32(1):87–93

    Article  CAS  PubMed  Google Scholar 

  14. Voelkl J, Tuffaha R, Luong TTD et al (2018) Zinc inhibits phosphate-induced vascular calcification through TNFAIP3-mediated suppression of NF-κB. 29(6):1636–48

  15. Pompano LMBE (2021) Effects of dose and duration of zinc interventions on risk factors for type 2 diabetes and cardiovascular disease: a systematic review and meta-analysis. Adv Nutr 12(1):141–160

    Article  PubMed  Google Scholar 

  16. Inker LA, Eneanya ND, Coresh J et al (2021) New creatinine- and cystatin c-based equations to estimate GFR without race. N Engl J Med 385(19):1737–1749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Takahashi A (2021) Carbon dioxide narcosis in the terminal stage of hemodialysis therapy: acase report with the possible pathophysiologies and the treatment methods. 9(4):2419–23

  18. Skalnaya MG, Skalny AV, Yurasov VV et al (2017) Serum trace elements and electrolytes are associated with Fasting Plasma Glucose and hba1c in postmenopausal women with type 2 diabetes mellitus. Biol Trace Elem Res 177(1):25–32

    Article  CAS  PubMed  Google Scholar 

  19. Braun J (1999) Erythrocyte zinc protoporphyrin. Kidney Int Suppl 69:S57-60

    Article  CAS  PubMed  Google Scholar 

  20. Kobayashi H, Abe M, Okada K et al (2015) Oral zinc supplementation reduces the erythropoietin responsiveness index in patients on hemodialysis. Nutrients 7(5):3783–3795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lytras A, Tolis G (2007) Assessment of endocrine and nutritional status in age-related catabolic states of muscle and bone. 10(5):604–10

  22. Takic M ZM, Terzic B,Stojsavljevic A,Mijuskovic M,Radjen S,Ristic-Medic D (2021) Zinc deficiency, plasma fatty acid profile and desaturase activities in hemodialysis patients: is supplementation necessary? Front Nutr 8(700450)

  23. **ang S, Yao Y, Wan Y et al (2016) Comparative study on trace element excretions between nonanuric and anuric patients undergoing continuous ambulatory peritoneal dialysis. 8(12):826

  24. Voelkl J, Cejka D, Alesutan I (2019) An overview of the mechanisms in vascular calcification during chronic kidney disease. Curr Opin Nephrol Hypertens 28(4):289–296

    Article  CAS  PubMed  Google Scholar 

  25. Agharazii M, St-Louis R, Gautier-Bastien A et al (2015) Inflammatory cytokines and reactive oxygen species as mediators of chronic kidney disease-related vascular calcification. Am J Hypertens 28(6):746–755

    Article  CAS  PubMed  Google Scholar 

  26. Düsing P, Zietzer A, Goody PR et al (2021) Vascular pathologies in chronic kidney disease: pathophysiological mechanisms and novel therapeutic approaches. J Mol Med (Berl) 99(3):335–348

    Article  PubMed  Google Scholar 

  27. Lee HLWKM, Ryoo HM, Baek JH (2010) Tumor necrosis factor-alpha increases alkaline phosphatase expression in vascular smooth muscle cells via MSX2 induction. Biochem Biophys Res Commun 391(1):1087–1092

    Article  CAS  PubMed  Google Scholar 

  28. Raaz U, Schellinger IN, Chernogubova E et al (2015) Transcription factor runx2 promotes aortic fibrosis and stiffness in type 2 diabetes mellitus. 117(6):513–24

  29. Yang X, Chen A, Liang Q et al (2021) Up-regulation of heme oxygenase-1 by celastrol alleviates oxidative stress and vascular calcification in chronic kidney disease. Free Radic Biol Med 172:530–540

    Article  CAS  PubMed  Google Scholar 

  30. Zalewski PD, Beltrame JF, Wawer AA, Abdo AI, Murgia C (2019) Roles for endothelial zinc homeostasis in vascular physiology and coronary artery disease. Crit Rev Food Sci Nutr 59(21):3511–3525

    Article  CAS  PubMed  Google Scholar 

  31. Thokala S, Bodiga VL, Kudle MR, Bodiga S (2019) Comparative response of cardiomyocyte ZIPs and ZnTs to extracellular zinc and TPEN. Biol Trace Elem Res 192(2):297–307

    Article  CAS  PubMed  Google Scholar 

  32. Maxel T, Svendsen PF, Smidt K et al (2017) Expression patterns and correlations with metabolic markers of zinc transporters ZIP14 and ZNT1 in obesity and polycystic ovary syndrome. Front Endocrinol 8

  33. Banaszak M, Górna I, Przysławski J (2021) Zinc and the innovative zinc-α2-glycoprotein adipokine play an important role in lipid metabolism: a critical review. Nutrients 13(6)

  34. Prasad AS (2014) Zinc is an antioxidant and anti-inflammatory agent: its role in human health. Front Nutr 1

  35. Takic M, Zekovic M, Terzic B et al (2021) Zinc deficiency, plasma fatty acid profile and desaturase activities in hemodialysis patients: is supplementation necessary? Front Nutr 8:700450

    Article  PubMed  PubMed Central  Google Scholar 

  36. Garagarza C, Valente A, Caetano C et al (2022) Zinc DEFICIENT intake in hemodialysis patients: a path to a high mortality risk. J Renal Nutr Off J Council Renal Nutr Natl Kidney Found 32(1):87–93

    Article  CAS  Google Scholar 

  37. Li J, Cao D, Huang Y et al (2022) Zinc intakes and health outcomes: an umbrella review. Front Nutr 9

  38. Knez M, Glibetic M (2021) Zinc as a biomarker of cardiovascular health. Front Nutr 8

  39. Wani AL, Hammad Ahmad Shadab GG, Afzal M (2021) Lead and zinc interactions - an influence of zinc over lead related toxic manifestations. J Trace Elem Med Biol 64:126702

    Article  CAS  PubMed  Google Scholar 

  40. Takahashi A (2022) Role of zinc and copper in erythropoiesis in patients on hemodialysis. J Ren Nutr 32(6):650–657

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research was funded by the Clinical Research Cultivation Program of the Second Hospital of Anhui Medical University Foundation, grant numbers 2020LCZD01, 2021LCYB14, and the Fundamental Research Cultivation Program of the Second Hospital of Anhui Medical University Foundation, grant numbers 2020GMFY04, 2021GQFY05.

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Authors

Contributions

Conceptualization, DZ and DW; methodology, DZ and YW; software, DZ; validation, DZ and DW; formal analysis, DZ and DW; investigation, HL, YW, WZ, and ZN; resources, HL, YW, WZ, and ZN.; data curation, DZ and DW; writing—original draft preparation, DZ; writing—review and editing, DZ and DW; supervision, DW; project administration, DW; funding acquisition, DZ. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Deguang Wang.

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The authors declare no competing interests.

Ethics Approval and Consent to Participate

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee for human research at the Second Hospital of Anhui Medical University (No: YJ-YX2017-004). Written informed consent has been obtained from the patients to publish this paper.

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Not applicable.

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The authors declare no competing interests.

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Danfeng Zhang and Yuvu Zhu are co-first authors for this paper.

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Zhang, D., Zhu, Y., Li, H. et al. Associations of Whole Blood Zinc Levels with Coronary Artery Calcification and Future Cardiovascular Events in CKD Patients. Biol Trace Elem Res 202, 46–55 (2024). https://doi.org/10.1007/s12011-023-03655-7

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  • DOI: https://doi.org/10.1007/s12011-023-03655-7

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