Increased Circulating Fetuin-A Levels in Patients With Atrial Fibrillation: Are We Really There?

Increased Circulatings; Fetuin-A Levels; Atrial Fibrillation; Diabetes Mellitus; Insulin Resistance; Metabolic Syndrome

Fetuin-A is a protein almost exclusively secreted by the liver. Circulating fetuin-A levels are elevated in humans with metabolic syndrome and insulin resistance, conditions that are associated with increased risk of cardiovascular disease.¹ Fetuin-A is a natural inhibitor of the insulin-stimulated insulin receptor tyrosine kinase and was shown to induce insulin resistance in rodents.²,³ Studies in humans have demonstrated that circulating fetuin-A levels are positively associated with fat accumulation in the liver, insulin resistance, and metabolic syndrome.⁴ To our knowledge, the potential association between fetuin-A and atrial fibrillation (AF) has not been studied to date. Therefore, the present study aimed to determine circulating fetuin-A levels in AF patients and revealed that higher plasma fetuin-A levels were associated with AF after adjustments for some confounding factors.

Fetuin-A seems to be involved in many normal and pathological processes, such as in response to systemic inflammation, hepatocyte-growth-factor activity and regulation of insulin activity, inhibition of unwanted mineralization, osteogenesis, and bone resorption.⁵

However, this study has some limitations such as the small number of patients included, and all patients were recruited from a single center. Thus, we cannot infer a causal relationship between fetuin-A elevation an AF. To clarify this issue, prospective large-scale studies, that begin before the onset of AF develops, are needed, as the authors state in the conclusion.⁶

Studies in humans have demonstrated that circulating fetuin-A levels are positively associated with fat accumulation in the liver, insulin resistance, metabolic syndrome, and diabetes mellitus, conditions that are associated with increased risk of cardiovascular disease and AF. Fetuin-A concentrations are strongly associated with the risk of myocardial infarction and ischemic stroke independent of standard risk factors. Additional research is warranted to elucidate the mechanisms by which fetuin-A influences the risk of cardiovascular disease and AF.¹

Despite the small number of individuals included, the study suggests the possibility of using fetuin-A concentrations in the prevention or early detection of cardiovascular events, such as AF, stroke, and their consequences.

References

• ¹
  Weikert C, Stefan N, Schulze MB, Pischon T, Berger K, Joost HG, et al. Plasma fetuin-a levels and the risk of myocardial infarction and ischemic stroke. Circulation. 2008 Dec 9;118(24):2555-62. doi: 10.1161/CIRCULATIONAHA.108.814418.
  » https://doi.org/10.1161/CIRCULATIONAHA.108.814418
• ²
  Denecke B, Graber S, Schafer C, Heiss A, Woltje M, Jahnen-Dechent W. Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem J. 2003;376 (Pt 1):135-45 doi: 10.1042/BJ20030676.
  » https://doi.org/10.1042/BJ20030676
• ³
  Rauth G, Poschke O, Fink E, Eulitz M, Tippmer S, Kellerer M, et al. The nucleotide and partial amino acid sequences of rat fetuin: identity with the natural tyrosine kinase inhibitor of the rat insulin receptor. Eur J Biochem. 1992;204(2):523-29. doi: 10.1111/j.1432-1033.1992.tb16663.x.
  » https://doi.org/10.1111/j.1432-1033.1992.tb16663.x
• ⁴
  Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Krober SM, et al. Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care. 2006;29(4):853-7. doi: 10.2337/diacare.29.04.06.dc05-1938.
  » https://doi.org/10.2337/diacare.29.04.06.dc05-1938
• ⁵
  Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA. Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation. 2006;113(14):1760-7. doi: 10.1161/CIRCULATIONAHA.105.588723.
  » https://doi.org/10.1161/CIRCULATIONAHA.105.588723
• ⁶
  Tekin G, Tekin YK, Aydın H, Nur N. Increased Circulating Fetuin-A Levels in Patients with Atrial Fibrillation. Int J Cardiovasc Sci. 2024; 37:e20220174. DOI: 10.36660/ijcs.20220174.
  » https://doi.org/10.36660/ijcs.20220174.

• Editorial referring to the article: Increased Circulating Fetuin-A Levels in Patients with Atrial Fibrillation

Publication Dates

• Publication in this collection
  04 Mar 2024
• Date of issue
  2024