Skip to main content

Advertisement

SpringerLink
Log in

Adipokines and coronary artery calcification in incident dialysis participants

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Adipokines have been associated with increased risk of cardiovascular disease. Our aim was to determine if adipokine levels are associated with coronary artery calcification (CAC) as well as all-cause mortality in incident dialysis patients.

Methods

In patients new to dialysis, we prospectively investigated the association of adiponectin, leptin and resistin with coronary artery calcification measured by ECG-gated computer tomography. Participants were recruited a median of two months after starting dialysis.

Results

The mean age was 50.0 (12.6) years and 31.1% were women. About 42% percent had BMI > 30. Higher adiponectin levels were inversely associated with CAC progression as change in Agatston score [−155.1 (−267.9, −42.2), p = 0.008] or change in CAC volumes between scans [−2.8 (−4.9, −0.6), p = 0.01]. Higher leptin levels were associated with CAC progression [110.4 (34.3–186.6), p = 0.005]. Decreased leptin [HR 0.5 (0.3–0.9), p = 0.05] was associated with all-cause mortality in adjusted models. There was no significant association between all-cause mortality and adiponectin [1.4 (0.6–3.4), p = 0.4] or resistin [HR 1.7 (0.5–5.0), p = 0.4].

Conclusion

High adiponectin protects against CAC progression, but is not associated with increased all-cause mortality. Higher leptin, as well as higher leptin to adiponectin ratio, is associated with CAC progression. Lower leptin levels were associated with all-cause mortality. The association of adipokines and cardiovascular disease in individuals on dialysis is complex and requires further study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. S.E. Rosas et al. Coronary artery calcification in renal transplant recipients. Am. J. Transpl. 5(8), 1942–1947 (2005)

    Article  Google Scholar 

  2. A.M. Khan et al. FGF-23 and the progression of coronary arterial calcification in patients new to dialysis. Clin. J. Am. Soc. Nephrol. 7(12), 2017–2022 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. H.J. Kramer et al. Increasing body mass index and obesity in the incident ESRD population. J. Am. Soc. Nephrol. 17(5), 1453–1459 (2006)

    Article  PubMed  Google Scholar 

  4. J.F. Briffa et al. Adipokines as a link between obesity and chronic kidney disease. Am. J. Physiol. Ren. Physiol. 305(12), F1629–F1636 (2013)

    Article  CAS  Google Scholar 

  5. T. Yamauchi et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7(8), 941–946 (2001).

    Article  CAS  PubMed  Google Scholar 

  6. A. Wiecek, M. Adamczak, J. Chudek, Adiponectin–an adipokine with unique metabolic properties. Nephrol. Dial. Transpl. 22(4), 981–988 (2007)

    Article  CAS  Google Scholar 

  7. X.H. Luo et al. Development of arterial calcification in adiponectin-deficient mice: adiponectin regulates arterial calcification. J. Bone Min. Res. 24(8), 1461–1468 (2009)

    Article  CAS  Google Scholar 

  8. D.M. Maahs et al. Low plasma adiponectin levels predict progression of coronary artery calcification. Circulation 111(6), 747–753 (2005)

    Article  CAS  PubMed  Google Scholar 

  9. M.B. Schulze et al. Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 54(2), 534–539 (2005)

    Article  CAS  PubMed  Google Scholar 

  10. M. Ai et al. Adiponectin: an independent risk factor for coronary heart disease in men in the Framingham offspring Study. Atherosclerosis 217(2), 543–548 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. K. Sharma et al. Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients. Kidney Int. 51(6), 1980–1985 (1997)

    Article  CAS  PubMed  Google Scholar 

  12. M. Zeadin et al. Effect of leptin on vascular calcification in apolipoprotein E-deficient mice. Arterioscler Thromb. Vasc. Biol. 29(12), 2069–2075 (2009)

    Article  CAS  PubMed  Google Scholar 

  13. E.L. Scheller et al. Leptin functions peripherally to regulate differentiation of mesenchymal progenitor cells. Stem Cells 28(6), 1071–1080 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. A. Scholze et al. Low serum leptin predicts mortality in patients with chronic kidney disease stage 5. Obes. (Silver Spring) 15(6), 1617–1622 (2007)

    Article  CAS  Google Scholar 

  15. F. Mallamaci, G. Tripepi, C. Zoccali, Leptin in end stage renal disease (ESRD): a link between fat mass, bone and the cardiovascular system. J. Nephrol. 18(4), 464–468 (2005)

    CAS  PubMed  Google Scholar 

  16. R. Kawamura et al. Circulating resistin is increased with decreasing renal function in a general Japanese population: the Hisayama Study. Nephrol. Dial. Transpl. 25(10), 3236–3240 (2010)

    Article  CAS  Google Scholar 

  17. S. Verma et al. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 108(6), 736–740 (2003)

    Article  CAS  PubMed  Google Scholar 

  18. A. Kunnari et al. High plasma resistin level is associated with enhanced highly sensitive C-reactive protein and leukocytes. J. Clin. Endocrinol. Metab. 91(7), 2755–2760 (2006)

    Article  CAS  PubMed  Google Scholar 

  19. A.S. Agatston et al. Quantification of coronary artery calcium using ultrafast computed tomography. J. Am. Coll. Cardiol. 15(4), 827–832 (1990)

    Article  CAS  PubMed  Google Scholar 

  20. J.E. Hokanson et al. Evaluating changes in coronary artery calcium: an analytic method that accounts for interscan variability. AJR Am. J. Roentgenol. 182(5), 1327–1332 (2004)

    Article  PubMed  Google Scholar 

  21. T. Kazumi et al. Serum adiponectin is associated with high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein particle size in young healthy men. Metabolism 53(5), 589–593 (2004)

    Article  CAS  PubMed  Google Scholar 

  22. C. Zoccali et al. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J. Am. Soc. Nephrol. 13(1), 134–141 (2002)

    Article  CAS  PubMed  Google Scholar 

  23. M. Rao et al. Plasma adiponectin levels and clinical outcomes among haemodialysis patients. Nephrol. Dial. Transpl. 23(8), 2619–2628 (2008)

    Article  CAS  Google Scholar 

  24. J.J. Diez et al. High stable serum adiponectin levels are associated with a better outcome in prevalent dialysis patients. Am. J. Nephrol. 30(3), 244–252 (2009)

    Article  CAS  PubMed  Google Scholar 

  25. F. Takemoto et al. Plasma adiponectin: a predictor of coronary heart disease in hemodialysis patients–a Japanese prospective eight-year study. Nephron Clin. Pr. 111(1), c12–c20 (2009)

    Article  CAS  Google Scholar 

  26. T. Sakura et al. The association of serum adiponectin with abdominal aortic calcification in Japanese male hemodialysis patients: a cross-sectional observational study. Sci. Rep. 7(1), 6434 (2017)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. B.A. Larsen et al. Adipokines and severity and progression of coronary artery calcium: findings from the Rancho Bernardo Study. Atherosclerosis 265, 1–6 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Anubhuti, S. Arora, Leptin and its metabolic interactions: an update. Diabetes Obes. Metab. 10(11), 973–993 (2008)

    Article  CAS  PubMed  Google Scholar 

  29. J.E. Ho, et al. Protein biomarkers of cardiovascular disease and mortality in the community. J. Am. Heart Assoc. 7(14), e008108 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. A. Rahmani et al. Association between plasma leptin/adiponectin ratios with the extent and severity of coronary artery disease. BMC Cardiovasc Disord. 20(1), 474 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. M.C. Lee et al. Serum leptin levels positively correlate with peripheral arterial stiffness in kidney transplantation patients. Transpl. Proc. 46(2), 353–358 (2014)

    Article  CAS  Google Scholar 

  32. P. Szulc et al. Positive association of high leptin level and abdominal aortic calcification in men- the prospective MINOS study. Circ. J. 82(12), 2954–2961 (2018)

    Article  CAS  PubMed  Google Scholar 

  33. A. Qasim et al. Adipokines, insulin resistance, and coronary artery calcification. J. Am. Coll. Cardiol. 52(3), 231–236 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. M.P. Reilly et al. Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes. J. Clin. Endocrinol. Metab. 89(8), 3872–3878 (2004)

    Article  CAS  PubMed  Google Scholar 

  35. C. Iribarren et al. Plasma leptin levels and coronary artery calcification in older adults. J. Clin. Endocrinol. Metab. 92(2), 729–732 (2007)

    Article  CAS  PubMed  Google Scholar 

  36. B. Varma, et al. Higher leptin levels are associated with coronary artery calcium progression: the multi-ethnic study of atherosclerosis (MESA).Diabet. Epidemiol. Manag. 6, 100047 (2022)

    Article  PubMed  Google Scholar 

  37. C. Aoqui et al. Increased visceral adiposity is associated with coronary artery calcification in male patients with chronic kidney disease. Eur. J. Clin. Nutr. 67(6), 610–614 (2013)

    Article  CAS  PubMed  Google Scholar 

  38. S.G. Wannamethee et al. The obesity paradox in men with coronary heart disease and heart failure: the role of muscle mass and leptin. Int. J. Cardiol. 171(1), 49–55 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  39. X. Bian et al. Association of leptin with mortality in patients on maintenance hemodialysis: a prospective study. Iran. J. Kidney Dis. 8(4), 314–320 (2014)

    PubMed  Google Scholar 

  40. S. Mishra et al. The association of serum leptin with mortality in older adults. PLoS ONE 10(10), e0140763 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. A. Scholze, M. Tepel, Role of leptin in reverse epidemiology in chronic kidney disease. Semin Dial. 20(6), 534–538 (2007)

    Article  PubMed  Google Scholar 

  42. M. Freemark, Metabolomics in nutrition research: biomarkers predicting mortality in children with severe acute malnutrition. Food Nutr. Bull. 36(1 Suppl), S88–S92 (2015)

    Article  PubMed  Google Scholar 

  43. J.M. Njunge et al. Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition. Sci. Rep. 9(1), 5981 (2019)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. G.M. Lord et al. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394(6696), 897–901 (1998)

    Article  CAS  PubMed  Google Scholar 

  45. R. Faggioni et al. Leptin deficiency enhances sensitivity to endotoxin-induced lethality. Am. J. Physiol. 276(1), R136–R142 (1999)

    CAS  PubMed  Google Scholar 

  46. G.S. Filippatos et al. Leptin serum levels in cachectic heart failure patients. Relationship with tumor necrosis factor-alpha system. Int J. Cardiol. 76(2–3), 117–122 (2000)

    Article  CAS  PubMed  Google Scholar 

  47. W. Wulaningsih et al. Serum leptin, C-reactive protein, and cancer mortality in the NHANES III. Cancer Med 5(1), 120–128 (2016)

    Article  CAS  PubMed  Google Scholar 

  48. M.P. Reilly et al. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111(7), 932–939 (2005)

    Article  CAS  PubMed  Google Scholar 

  49. C.M. Steppan et al. The hormone resistin links obesity to diabetes. Nature 409(6818), 307–312 (2001)

    Article  CAS  PubMed  Google Scholar 

  50. J. Axelsson et al. Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance. Kidney Int. 69(3), 596–604 (2006)

    Article  CAS  PubMed  Google Scholar 

  51. K.M. Utzschneider et al. Resistin is not associated with insulin sensitivity or the metabolic syndrome in humans. Diabetologia 48(11), 2330–2333 (2005)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank the research coordinators and patients involved in this study.

Funding

This work was supported by NIH grants R21 HL 086971. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Funding sources had no involvement in study design, data collection, analysis, and interpretation, writing of the report, or decision to submit the paper for publication.

Author information

Author notes

  1. These authors contributed equally: Neil Roy, Danny Haddad

Authors and Affiliations

  1. Kidney and Hypertension Unit, Joslin Diabetes Center, Boston, MA, USA

    Neil Roy & Sylvia E. Rosas

  2. Harvard Medical School, Boston, MA, USA

    Neil Roy & Sylvia E. Rosas

  3. RWJ Barnabas -Jersey City Medical Center, Jersey City, NJ, USA

    Danny Haddad

  4. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Wei Yang

Authors
  1. Neil Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Danny Haddad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sylvia E. Rosas
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

N.R., D.H., W.Y. and S.E.R. met the ICMJE. criteria for authorship. Research idea and study design: SER; data acquisition: SER; data analysis/interpretation: N.R., D.H., W.Y., S.E.R.; statistical analysis: N.R., D.H., W.Y., S.E.R. supervision or mentorship: S.E.R. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Sylvia E. Rosas.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Informed consent

Informed consent has been obtained from the patients.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Roy, N., Haddad, D., Yang, W. et al. Adipokines and coronary artery calcification in incident dialysis participants. Endocrine 77, 272–280 (2022). https://doi.org/10.1007/s12020-022-03111-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-022-03111-x

Keywords

Search

Navigation