EVALUATING FGF-23 AS A MARKER FOR VULNERABLE CAROTID PLAQUES: A SYSTEMATIC REVIEW OF THE LITERATURE

Dr. Dennis Grantham

doi:10.55640/

Open Access

EVALUATING FGF-23 AS A MARKER FOR VULNERABLE CAROTID PLAQUES: A SYSTEMATIC REVIEW OF THE LITERATURE

https://doi.org/10.55640/

pdf

Dr. Dennis Grantham ¹ ,

⁴ Department of Cardiology, University of California, San Francisco (UCSF), San Francisco, USA

Abstract

Carotid atherosclerosis, a leading cause of ischemic stroke, is characterized by the formation of plaques that can rupture and lead to embolization. Identifying vulnerable plaques that are at high risk of rupture is critical for preventing ischemic events. Fibroblast growth factor-23 (FGF-23) is a hormone primarily involved in phosphate homeostasis and mineral metabolism, but recent studies have indicated its potential role as a biomarker for cardiovascular diseases, including atherosclerosis. This systematic review aims to explore the current evidence regarding FGF-23 as a biomarker for carotid plaque vulnerability. We reviewed studies that assessed FGF-23 levels in individuals with carotid artery disease and its association with plaque morphology, instability, and cardiovascular events. Our findings suggest that elevated FGF-23 levels correlate with increased carotid plaque vulnerability, highlighting its potential utility in early identification of high-risk plaques. However, further large-scale prospective studies are needed to establish its clinical value and reliability as a biomarker.

Keywords

Fibroblast growth factor-23, carotid artery, plaque vulnerability

References

📄 Dossabhoy, S.; Arya, S. Epidemiology of atherosclerotic carotid artery disease. Semin. Vasc. Surg. 2021, 34, 3–9. [Google Scholar] [CrossRef] [PubMed]

📄 Bejot, Y.; Bailly, H.; Durier, J.; Giroud, M. Epidemiology of stroke in Europe and trends for the 21st century. Presse Méd. 2016, 45 Pt 2, e391–e398. [Google Scholar] [CrossRef] [PubMed]

📄 Naylor, A.R.; Ricco, J.B.; de Borst, G.J.; Debus, S.; de Haro, J.; Halliday, A.; Hamilton, G.; Kakisis, J.; Kakkos, S.; Lepidi, S.; et al. Editor’s Choice—Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur. J. Vasc. Endovasc. Surg. 2018, 55, 3–81. [Google Scholar] [CrossRef]

📄 Shinohara, Y.; Nagayama, M.; Origasa, H. Postpublication external review of the Japanese guidelines for the management of stroke 2004. Stroke 2009, 40, 1439–1443. [Google Scholar] [CrossRef] [PubMed]

📄 Naylor, R.; Rantner, B.; Ancetti, S.; de Borst, G.J.; De Carlo, M.; Halliday, A.; Kakkos, S.K.; Markus, H.S.; McCabe, D.J.H.; Sillesen, H.; et al. Editor’s Choice—European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease. Eur. J. Vasc. Endovasc. Surg. 2023, 65, 7–111. [Google Scholar] [CrossRef]

📄 Verhoeven, B.A.; de Vries, J.P.; Pasterkamp, G.; Ackerstaff, R.G.; Schoneveld, A.H.; Velema, E.; de Kleijn, D.P.; Moll, F.L. Carotid atherosclerotic plaque characteristics are associated with microembolization during carotid endarterectomy and procedural outcome. Stroke 2005, 36, 1735–1740. [Google Scholar] [CrossRef]

📄 Niculescu, R.; Russu, E.; Arbanasi, E.M.; Kaller, R.; Arbanasi, E.M.; Melinte, R.M.; Cosarca, C.M.; Cocuz, I.G.; Sabau, A.H.; Tinca, A.C.; et al. Carotid Plaque Features and Inflammatory Biomarkers as Predictors of Restenosis and Mortality Following Carotid Endarterectomy. Int. J. Environ. Res. Public Health 2022, 19, 13934. [Google Scholar] [CrossRef]

📄 Miceli, G.; Basso, M.G.; Pintus, C.; Pennacchio, A.R.; Cocciola, E.; Cuffaro, M.; Profita, M.; Rizzo, G.; Tuttolomondo, A. Molecular Pathways of Vulnerable Carotid Plaques at Risk of Ischemic Stroke: A Narrative Review. Int. J. Mol. Sci. 2024, 25, 4351. [Google Scholar] [CrossRef]

📄 Seiler, S.; Reichart, B.; Roth, D.; Seibert, E.; Fliser, D.; Heine, G.H. FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment. Nephrol. Dial. Transplant. 2010, 25, 3983–3989. [Google Scholar] [CrossRef]

📄 Kumar, T.; Mohanty, S.; Rani, A.; Malik, A.; Kumar, R.; Bhashker, G. Fibroblast Growth Factor-23 in Pre-Dialysis Chronic Kidney Disease Patients and its Correlation with Carotid Artery Calcification. Indian J. Nephrol. 2022, 32, 560–566. [Google Scholar] [CrossRef]

📄 Yilmaz, G.; Ustundag, S.; Temizoz, O.; Sut, N.; Demir, M.; Ermis, V.; Sevinc, C.; Ustundag, A. Fibroblast Growth Factor-23 and Carotid Artery Intima Media Thickness in Chronic Kidney Disease. Clin. Lab. 2015, 61, 1061–1070. [Google Scholar] [CrossRef] [PubMed]

📄 Chang, Y.; Kim, J.; Woo, H.G.; Ryu, D.R.; Oh, H.J.; Song, T.J. Plasma Fibroblast Growth Factor 23 Concentration Is Associated with Intracranial Cerebral Atherosclerosis in Acute Ischemic Stroke Patients. J. Clin. Neurol. 2020, 16, 29–36. [Google Scholar] [CrossRef] [PubMed]

📄 Lim, K.; Lu, T.S.; Molostvov, G.; Lee, C.; Lam, F.T.; Zehnder, D.; Hsiao, L.L. Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation 2012, 125, 2243–2255. [Google Scholar] [CrossRef]

📄 Mencke, R.; Harms, G.; Mirkovic, K.; Struik, J.; Van Ark, J.; Van Loon, E.; Verkaik, M.; De Borst, M.H.; Zeebregts, C.J.; Hoenderop, J.G.; et al. Membrane-bound Klotho is not expressed endogenously in healthy or uraemic human vascular tissue. Cardiovasc. Res. 2015, 108, 220–231. [Google Scholar] [CrossRef]

📄 Kuro, O.M. The FGF23 and Klotho system beyond mineral metabolism. Clin. Exp. Nephrol. 2017, 21, 64–69. [Google Scholar] [CrossRef]

📄 Donate-Correa, J.; Muros de Fuentes, M.; Mora-Fernandez, C.; Navarro-Gonzalez, J.F. Pathophysiological implications of fibroblast growth factor-23 and Klotho and their potential role as clinical biomarkers. Clin. Chem. 2014, 60, 933–940. [Google Scholar] [CrossRef]

📄 Vogt, I.; Haffner, D.; Leifheit-Nestler, M. FGF23 and Phosphate-Cardiovascular Toxins in CKD. Toxins 2019, 11, 647. [Google Scholar] [CrossRef] [PubMed]

📄 Edmonston, D.; Grabner, A.; Wolf, M. FGF23 and klotho at the intersection of kidney and cardiovascular disease. Nat. Rev. Cardiol. 2024, 21, 11–24. [Google Scholar] [CrossRef]

📄 Marthi, A.; Donovan, K.; Haynes, R.; Wheeler, D.C.; Baigent, C.; Rooney, C.M.; Landray, M.J.; Moe, S.M.; Yang, J.; Holland, L.; et al. Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis. J. Am. Soc. Nephrol. 2018, 29, 2015–2027. [Google Scholar] [CrossRef]

📄 Rodriguez-Ortiz, M.E.; Alcala-Diaz, J.F.; Canalejo, A.; Torres-Pena, J.D.; Gomez-Delgado, F.; Munoz-Castaneda, J.R.; Delgado-Lista, J.; Rodriguez, M.; Lopez-Miranda, J.; Almaden, Y. Fibroblast growth factor 23 predicts carotid atherosclerosis in individuals without kidney disease. The CORDIOPREV study. Eur. J. Intern. Med. 2020, 74, 79–85. [Google Scholar] [CrossRef]

📄 Shah, N.H.; Dong, C.; Elkind, M.S.; Sacco, R.L.; Mendez, A.J.; Hudson, B.I.; Silverberg, S.; Wolf, M.; Rundek, T.; Wright, C.B. Fibroblast Growth Factor 23 Is Associated With Carotid Plaque Presence and Area: The Northern Manhattan Study. Arterioscler. Thromb. Vasc. Biol. 2015, 35, 2048–2053. [Google Scholar] [CrossRef]

📄 Biscetti, F.; Straface, G.; Porreca, C.F.; Bertoletti, G.; Vincenzoni, C.; Snider, F.; Stigliano, E.; Arena, V.; Angelini, F.; Pecorini, G.; et al. Increased FGF23 serum level is associated with unstable carotid plaque in type 2 diabetic subjects with internal carotid stenosis. Cardiovasc. Diabetol. 2015, 14, 139. [Google Scholar] [CrossRef] [PubMed]

📄 Del Porto, F.; Proietta, M.; di Gioia, C.; Cifani, N.; Dito, R.; Fantozzi, C.; Ferri, L.; Fabriani, L.; Rossi, M.; Tritapepe, L.; et al. FGF-23 levels in patients with critical carotid artery stenosis. Intern. Emerg. Med. 2015, 10, 437–444. [Google Scholar] [CrossRef]

📄 Zamani, M.; Skagen, K.; Lindberg, B.; Bjerkeli, V.; Aukrust, P.; Halvorsen, B.; Skjelland, M. Relationship between fibroblast growth factor in plasma and carotid plaque neovascularization: A pilot study. Front. Immunol. 2024, 15, 1385377. [Google Scholar] [CrossRef] [PubMed]

📄 Bi, J.; Zheng, M.; Li, K.; Sun, S.; Zhang, Z.; Yan, N.; Li, X. Relationships of serum FGF23 and alpha-klotho with atherosclerosis in patients with type 2 diabetes mellitus. Cardiovasc. Diabetol. 2024, 23, 128. [Google Scholar] [CrossRef]

How to Cite

EVALUATING FGF-23 AS A MARKER FOR VULNERABLE CAROTID PLAQUES: A SYSTEMATIC REVIEW OF THE LITERATURE. (2025). Global Journal of Medical and Pharmaceutical Sciences, 4(04), 1-7. https://doi.org/10.55640/