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Glycoproteins: Emerging Markers of Inflammation

Cardiovascular events can occur even when conventional risk factors are controlled.

Inflammation plays several roles in the development of atherosclerotic cardiovascular disease. As an alternative to traditional inflammatory markers, new biomarkers of systemic inflammation. Such as Glyc-A and Glyc-B, measured by nuclear magnetic resonance (NMR), have been studied.

Glyc-A has been associated as a marker of systemic inflammation. It measures both protein concentrations and glycosylation levels of specific proteins produced in the liver. The proteins that contribute most to the Glyc-A signal in NMR include acute-phase reactants like alpha-1-acid glycoprotein, haptoglobin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and transferrin [1].

Espectro RMN que indica la inflamación de glicoproteínas-Glycoproteins-Glycoprotéines
NMR spectrum indicating the inflammation of GlycA and GlycB.

It has also been observed that Glyc-A levels are higher in chronic inflammatory diseases [2,3]. They are able to reflect a better systemic inflammatory response than a single glycoprotein component, as it is a stable marker with lower variability over time [4].

Glyc-A is not only a marker of systemic inflammation but is also associated with inflammation in conditions of cardiometabolic risk, such as obesity, insulin resistance, and metabolic syndrome. Thus, in chronic inflammatory diseases with low-grade inflammation, Glyc-A could serve as a biomarker for both inflammatory activity and cardiometabolic risk.

It has been shown that Glyc-A is associated with subclinical atherosclerosis [5] and cardiovascular disease [6]. Its levels increase in cases of acute and chronic inflammation, as circulating concentrations and the glycosylation pattern of these proteins change. Additionally, high Glyc-A levels have been linked to an increased risk of cardiovascular events, regardless of traditional risk factors [7] and high-sensitivity C-reactive protein [8], another inflammatory marker.

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    1. Otvos, J. D., Guyton, J. R., Connelly, M. A., Akapame, S., Bittner, V., Kopecky, S. L., … & Boden, W. E. (2018). Relations of GlycA and lipoprotein particle subspecies with cardiovascular events and mortality: a post hoc analysis of the AIM-HIGH trial.Journal of clinical lipidology, 12(2), 348-355.
    2. Rodríguez-Carrio, J., Alperi-López, M., López, P., Pérez-Álvarez, Á. I., Gil-Serret, M., Amigó, N., …& Suárez, A. (2020). GlycA levels during the earliest stages of rheumatoid arthritis: potential use as a biomarker of subclinical cardiovascular disease. Journal of Clinical Medicine, 9(8), 2472.
    3. Malo, A. I., Rull, A., Girona, J., Domingo, P., Fuertes-Martín, R., Amigó, N., … & Masana, L. (2020).Glycoprotein profile assessed by 1H-NMR as a global inflammation marker in patients with HIV infection. A prospective study. Journal of Clinical Medicine, 9(5), 1344.
    4. Connelly, M. A., Gruppen, E. G., Otvos, J. D., & Dullaart, R. P. (2016). Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer. Clinica Chimica Acta, 459, 177-186.
    5. Tibuakuu, M., Fashanu, O. E., Di, Z. H. A. O., Otvos, J. D., Brown, T. T., Haberlen, S. A., …& MICHOS, E. D. (2019). GlycA, a novel inflammatory marker, is associated with subclinical coronary disease in the multicenter AIDS cohort study. AIDS (London, England), 33(3), 547.
    6. Cediel, G., Teis, A., Codina, P., Julve, J., Domingo, M., Santiago-Vacas, E., …& Bayés-Genís, A. (2022). GlycA and GlycB as inflammatory markers in chronic heart failure. The American Journal of Cardiology, 181, 79-86.
    7. Connelly, M. A., Otvos, J. D., Shalaurova, I., Playford, M. P., & Mehta, N. N. (2017). GlycA, a novel biomarker of systemic inflammation and cardiovascular disease risk.Journal of translational medicine, 15(1), 1-5.
    8. Akinkuolie, A. O., Glynn, R. J., Padmanabhan, L., Ridker, P. M., & Mora, S. (2016). Circulating N‐linked glycoprotein side‐chain biomarker, rosuvastatin therapy, and incident cardiovascular disease: An analysis from the JUPITER trial.Journal of the American Heart Association, 5(7), e003822.