Download biomedica product listFGF23 (Fibroblast Growth Factor 23), a well-known marker for phosphate metabolism, has achieved independent significance in the cardiovascular system [1]. Several large-scale prospective studies have established FGF23 as an independent risk marker for heart failure and mortality [2,3]. There is also growing evidence that FGF-23 levels can predict the response to therapies aimed to reduce heart failure risk [4].
FGF23 is expressed in the heart and is significantly elevated in heart failure
Recent studies indicate that FGF23 is also expressed in the heart [5]. It is significantly enhanced in clinical and experimental settings of cardiac remodeling and heart failure independent of renal function [6, 10]. Secreted by cardiac myocytes, FGF23 can stimulate pro-fibrotic factors in myocytes to induce fibrosis-related pathways in fibroblasts and consequently cardiac fibrosis. While acting on cardiac myocytes, FGF23 directly induces pro-hypertrophic genes and promotes the progression of LVH (left ventricular hypertrophy) in an autocrine and paracrine fashion. Thus, enhanced FGF23 may promote cardiac injury in various clinical settings by endocrine and paracrine/autocrine mechanisms [7].
FGF23 measurement for prognosis and risk assessment in heart failure
Several large-scale prospective studies show a linear correlation between FGF23 levels and mortality risk, particularly because of LVH and systolic heart insufficiency (heart failure with reduced ejection fraction, HFREF) [2,8]. This clinically evident association between HFREF and FGF23, is likely explained by FGF23 ‘s direct cardiotoxic effects on cardiomyocytes.
Besides the known risk markers in HFREF patients such as serum sodium and BNP, the measurement of FGF23 can thus be of considerable use for risk stratification of individual patients. Of special relevance is the growing evidence that FGF23 levels can predict the response to a therapy with a blocker of the renin-angiotensin-aldosterone system [9].
Cardiovascular risk assessment under ACE therapy
In the PEACE Study (Prevention of Events With Angiotensin-Converting Enzyme) FGF23 was determined in 3,627 patients with stable ischemic heart disease (SIHD) [4]. Increased FGF23 levels correlated, with mortality rate and heart failure, but also identified those patients who benefitted significantly from treatment with ACE inhibitor. This effect was independent of renal function. These results indicate that FGF23 may become an attractive tool for individualized HFREF therapy. Patients with cardiorenal syndrome (combined heart and kidney failure) may benefit from FGF23 determination for estimation of individual risk and initiation of individualized treatment.
FGF23 and therapy monitoring
Patients with kidney disease show elevated serum concentrations of FGF23, associated with cardiovascular and all-cause mortality. A therapeutic approach to reduce increased FGF23 levels is the administration of (calcium-free) phosphatebinders (calcimimetics). The „EVOLVE“ study (2,985 patients receiving hemodialysis with secondary Hyperparathyroidism), demonstrated that treatment-induced reductions in serum FGF23 were associated with lower rates of cardiovascular death and major cardiovascular events. Among patients randomized to cinacalcet, a ≥30% reduction in serum FGF23 between baseline and week 20 was associated with a reduction in the relative hazard of the clinically relevant end point, cardiovascular mortality, sudden cardiac death, and heart failure [9].
Further studies on FGF23
Clearly more experimental and clinical studies are required to justify integrating routine measurement of FGF23 as risk marker for heart failure or to guide treatment. However, it is one of the few promising biomarkers that has high potential to ascertain the effect of FGF23 specific therapeutic interventions on clinically relevant endpoints [10].
Literature
[1] Hu MG, Shiizaki K, Kuro-o M, Moe OW. Fibroblast Growth Factor 23 and Klotho: Physiology and Pathophysiology of an Endocrine Network of Mineral Metabolism. Annu Rev Physiol. 2013;75:503-33.
[2] Brandenburg VM, Kleber ME, Vervloet MG, Tomaschitz A, Pilz S, Stojakovic T, Delgado G, Grammer TB, Marx N, März W, Scharnagl H. Fibroblast growth factor 23(FGF23) and mortality: the Ludwigshafen Risk and Cardiovascular Health Study. Atherosclerosis. 2014 Nov;237(1):53-9.
[3] Olauson H, Vervloet MG, Cozzolino M, Massy ZA, Ureña Torres P, Larsson TE. New insights into the FGF23-Klotho axis. Semin Nephrol. 2014 Nov;34(6):586-97.
[4] Udell JA, Morrow DA, Jarolim P, Sloan S, Hoffman EB, O’Donnell TF, Vora AN,Omland T, Solomon SD, Pfeffer MA, Braunwald E, Sabatine MS. Fibroblast growth factor-23, cardiovascular prognosis, and benefit of angiotensin-converting enzyme inhibition in stable ischemic heart disease. J Am Coll Cardiol. 2014 Jun 10;63(22):2421-8
[5] Itoh N, Ohta H, Nakayama Y, Konishi M. Roles of FGF signals in heart development, health, and disease. Front Cell Dev Biol (2016) 4:110. doi:10.3389/fcell.2016.00110.
[6] Andrukhova O, Slavic S, Odorfer KI, Erben RG. Experimental myocardial infarction upregulates circulating fibroblast growth factor-23. J Bone Miner Res (2015) 30:1831–9. doi:10.1002/jbmr.2527.
[7] Leifheit-Nestler M and Haffner D. Paracrine effects of FGF23 on the Heart. Frontiers in Endocrinology | www.frontiersin.org May 2018 | Volume 9 | Article 278.
[8] Almahmoud MF, Soliman EZ, Bertoni AG, Kestenbaum B, Katz R, Lima JAC, Ouyang P, Miller PE, Michos ED, Herrington DM; Fibroblast Growth Factor-23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA. J Am Heart Assoc. 2018 Sep 18;7(18):e008334.
[9] Moe SM, Chertow GM, Parfrey PS, Kubo Y, Block GA, Correa-Rotter R, Drüeke TB, Herzog CA, London GM, Mahaffey KW, Wheeler DC, Stolina M, Dehmel B, Goodman WG, Floege J; For the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators. Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial. Circulation. 2015 July;132(1):27-39
[10] Vervloet M; Renal and Extrarenal Effects of Fibroblast Growth Factor 23. Nature Reviews. Nephrology 15, Nr. 2 (Februar 2019): 109–20.
Read more on our fully validated and CE marked FGF-23 (intact) ELISA and FGF-23 (C-terminal) multi-matrix ELISA for IVD use.
Features and Benefits
- RELIABLE and FULLY VALIDATED for plasma samples – according to ICH Q2
- FAST ONE-STEP ELISA – only 3.5 h total incubation time
- PLASMA-BASED STANDARDS and CONTROLS INCLUDED – for biologically reliable data
- CHARACTERIZED MONOCLONAL ANTIBODIES – high specificity and sensitivity guaranteed
- COMPARABLE RESULTS – correlates with existing methods