Is serum Fibroblast Growth Factor 21 associated with the severity or presence of coronary artery disease?
FGF-21 and coronary artery disease
Abstract
Aim: Recent studies have shown that increased circulating concentrations of fibroblast growth factor 21 (FGF21) are associated with obesity, metabolic disorder, and atherosclerosis. However, the studies which investigate the relationship between serum FGF21 levels and coronary artery disease (CAD) include conflicting data. In this study, we planned to investigate the role of FGF21 in CAD development and CAD severity.
Method: Seventy-eight patients with stable angina pectoris (SA) (lesion positive) and 40 control patients (lesion negative) with similar cardiovascular risk factors who underwent coronary angiography were included in the study. Serum FGF21 levels were measured by ELISA method. CAD severity was evaluated by using SYNTAX and GENSINI risk scores.
Results: Although there was a statistically significant difference between serum FGF21 levels in the SA and the control groups [101.18 ± 141.62 vs. 47.93 ± 58.74 pg/mL; p = 0.03], no correlation was found between the SYNTAX (r = 0.146 and p = 0.134) and GENSINI (r = 0.211 and p = 0.084) scores with serum FGF21 levels. The SA group had lower serum HDL-C levels (41.57 ± 11.40 vs. 54.90 ± 34.47; p = 0.02). There was a significant and negative relationship between serum FGF21 and serum HDL-C levels in correlation analysis (r = - 0.272; p = 0.026).
Conclusion: The serum FGF21 levels are different between SA diagnosed and control patients. FGF21 may be a marker for CAD diagnosis, but not for the evaluation of CAD severity. To the best of our knowledge, this is the first study to evaluate coronary artery disease severity together with a lipid profile.
References
2) Domouzoglou EM, Naka KK, Vlahos AP, et al. Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21. Am J Physiol Heart Circ Physiol 2015;309:1029-1038. https://pubmed.ncbi.nlm.nih.gov/26232236/
3) Jing C, X Su, Lei Q, et al. Circulating level of fibroblast growth factor 21 is independently associated with the risks of unstable angina pectoris. Bioscience Reports (2018) 38 BSR20181099 https://pubmed.ncbi.nlm.nih.gov/30185439/
4) Boesen ME, Singh D, Menon BK, et al. A systematic literature review of the effect of carotid atherosclerosis on local vessel stiffness and elasticity. Atherosclerosis 2015;243:211-222. https://pubmed.ncbi.nlm.nih.gov/26402140/
5) Kousios A, Kouis P, Panayiotou AG. Matrix metalloproteinases and subclinical atherosclerosis in chronic kidney disease: A systematic review. Int J Nephrol 2016; 2016: 9498013, doi: 10.1155/2016/9498013. https://pubmed.ncbi.nlm.nih.gov/27042350/
6) Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic andregulatory pathways. Physiol Rev 2006;86:515-581. https://pubmed.ncbi.nlm.nih.gov/16601268/
7) Weber C, Zernecke A, Libby P. The multifaceted contributionsof leukocyte subsets to atherosclerosis: lessons from mousemodels. Nat Rev Immunol 2008;8:802-815. https://pubmed.ncbi.nlm.nih.gov/18825131/
8) Crickx E, Saussine A, Vignon-Pennamen MD, et al. Diffuse dermal angiomatosis associated with severe atherosclerosis: Two cases and review of the literature. Clin Exp Dermatol 2015;40:521-524. https://pubmed.ncbi.nlm.nih.gov/25639294/
9) Itoh N, Ornitz DM. Evolution of the FGF and FGFr gene families. Trends Genet 2004; 20: 563-569. https://pubmed.ncbi.nlm.nih.gov/15475116/
10) Presta M, Dell’Era P, Mitola S, et al. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 2005; 16: 159-178. https://pubmed.ncbi.nlm.nih.gov/15863032/
11) Shen Y, Ma X, Zhou J, et al. Additive relationship between serum fibroblast growth factor 21 level and coronary artery disease. Cardiovasc Diabetol 2013;12:124. doi: 10.1186/1475-2840-12-124. https://pubmed.ncbi.nlm.nih.gov/23981342/
12) Li H, Zhang J, Jia W. Fibroblast growth factor 21: A novel metabolic regulator from pharmacology to physiology. Front Med. 2013;7:25–30. https://pubmed.ncbi.nlm.nih.gov/23358894/
13) Kharitonenkov A, Shiyanova TL, Koester A, et al. FGF21 as a novel metabolic regulator. J Clin Invest 2005; 115: 1627-1635. https://pubmed.ncbi.nlm.nih.gov/15902306/
14) Semba RD, Sun K, Egan JM, et al. Relationship of serum fibroblast growth factor 21 with abnormal glucose metabolism and insulin resistance: the Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2012; 97:1375–1382. https://pubmed.ncbi.nlm.nih.gov/22344195/
15) Coskun T, Bina HA, Schneider MA, et al. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 2008;149:6018–6027. https://pubmed.ncbi.nlm.nih.gov/18687777/
16) Bobbert T, Schwarz F, Fischer-Rosinsky A, et al. Fibroblast growth factor 21 predicts the metabolic syndrome and type 2 diabetes in Caucasians. Diabetes Care. 2013;36(1):145-149. https://pubmed.ncbi.nlm.nih.gov/22933429/
17) Khalaf MM, Fayez S, Azou T. Serum Fibroblast Growth Factor 21 as a Novel Biomarker in Prediction of Coronary Artery Disease Severity.British Journal of Medicine & Medical Research 2016; 18(9): 1-11. https://pubmed.ncbi.nlm.nih.gov/26232236/
18) Kokkinos J, Tang S, Rye KA, et al. The role of fibroblast growth factor 21 in atherosclerosis. Atherosclerosis 2017;257:259-265. https://pubmed.ncbi.nlm.nih.gov/28012645/
19) Lin Z, Pan X, Wu F et al. Fibroblast growth factor 21 prevents atherosclerosis by supression of hepatic sterol regulatory element-binding protein-2 and induction of adiponectin in mice. Circulation. 2015;131:1861-1871. https://pubmed.ncbi.nlm.nih.gov/25794851/
20) Monsour HP, Frenette CT, Wyne K. Fatty liver: a link to cardiovascular disease-its natural history, pathogenesis, and treatment. Methodist Debakey Cardiovasc J 2013; 8:21–25. https://pubmed.ncbi.nlm.nih.gov/23227282/
21) American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019;42:13-28. https://pubmed.ncbi.nlm.nih.gov/30559228/
22) Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013;34:2159–2219 https://pubmed.ncbi.nlm.nih.gov/23771844/
23) Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract 2017; 23:1–87. https://pubmed.ncbi.nlm.nih.gov/28437620/
24) SYNTAX working group. SYNTAX score calculator. Available at http://www.syntaxscore.com. Accessed May 20, 2012
25) Gensini GG. Coronary arteriography: role in myocardial revascularization. Postgrad Med 1978;63(1):121- 128. https://pubmed.ncbi.nlm.nih.gov/637926/
26) Qing L, Yuan Z, Ding D, et al. Association Between Serum Fibroblast Growth Factor 21 and Mortality Among Patients With Coronary Artery Disease. J Clin Endocrinol Metab, 2016; 101(12):4886–4894. https://pubmed.ncbi.nlm.nih.gov/27662438/
27) Stein S, Stepan H, Kratzsch J, et al. Serum fibroblast growth factor 21 levels in gestational diabetes mellitus in relation to insulin resistance and dyslipidemia. Metabolism 2010;59:33–37. https://pubmed.ncbi.nlm.nih.gov/19699495/
28) Liu SQ, Roberts D, Kharitonenkov A, et al. Endocrine protection of ischemic myocardium by FGF21 from the liver and adipose tissue. Scientific Reports. 2013;3: 2767. https://doi.org/10.1038/ srep02767. https://pubmed.ncbi.nlm.nih.gov/24067542/
29) Liu SQ, Tefft BJ, Roberts DT, et al. Cardioprotective proteins upregulated in the liver in response to experimental myocardial ischemia. American Journal of Physiology-Heart and Circulatory Physiology. 2012;303(12):1446–1458. https://pubmed.ncbi.nlm.nih.gov/23064833/
30) An SY, Lee MS, Yi SA, et al. Serum fibroblast growth factor 21 was elevated in subjects with type 2 diabetes mellitus and was associated with the presence of carotid artery plaques. Diabetes Res Clin Pract 2012; 96: 196-203. https://pubmed.ncbi.nlm.nih.gov/22293928/
31) Haifeng C, Nan L, Meifan Z, et al. A high circulating FGF21 level as a prognostic marker in patients with acute myocardial infarction. Am J Transl Res 2018;10(9):2958-2966. https://pubmed.ncbi.nlm.nih.gov/30323882/
32) Lee Y, Lim S, Hong ES, et al. Serum FGF21 concentration is associated with hypertriglyceridaemia, hyperinsulinaemia and pericardial fat accumulation, independently of obesity, but not with current coronary artery status. Clinical Endocrinology 2014; 80:57–64. https://pubmed.ncbi.nlm.nih.gov/23278761/
33) Matej Stancík. Fibroblast growth factor 21 in prediction of coronary angiography result in stable coronary artery disease patients. Biomed Res DOI: 10.4066/biomedicalresearch-C7-020. https://www.biomedres.info/proceedings/fibroblast-growth-factor-21-in-prediction-of-coronary-angiography-result-in-stable-coronary-artery-disease-patients-2889.html
34) Wang JS, Sheu, WH, Lee, WJ et al. Associations of fibroblast growth factor 21 with cardiovascular risk and β-cell function in patients who had no history of diabetes. Clin. Chim. Acta 2017;(472) 80–85. https://pubmed.ncbi.nlm.nih.gov/28735064/
35) Ling WT, Tian J, Ling HS et al. Proteomic study on the protective mechanism of fibroblast growth factor 21 to ischemia-reperfusion injury. Can. J. Physiol. Pharmacol. 2013; (91):973–984. https://pubmed.ncbi.nlm.nih.gov/24117266/
36) Miyazaki Y, Saita E, Kishimoto Y, et al. Low Plasma Levels of Fibroblast Growth Factor-21 in Patients with Peripheral Artery Disease.Journal of atherosclerosis and thrombosis. 2018;(25):9:821-828. https://pubmed.ncbi.nlm.nih.gov/29367522/
37) Park SD, Bae KH , Choi YK et al. Relationship between Circulating FGF21 Concentrations and the Severity of Coronary Artery Damage in Subjects with Cardiovascular Disease. J Lipid Atheroscler. 2018 ;7(1):42-49. https://e-jla.org/DOIx.php?id=10.12997/jla.2018.7.1.42
38) Kim WJ, Kim SS, Lee HC, et al. Association between serum fibroblast growth factor 21 and coronary artery disease in patients with type 2 diabetes. J Korean Med Sci 2015;30:586-590. https://pubmed.ncbi.nlm.nih.gov/25931789/
39) Matuszek B, Lenart-Lipińska M, Duma D, et al. Evaluation of concentrations of FGF21 a new adipocytokine in type 2 diabetes. Polish Journal of Endocrinology 2010;61:50-54. https://pubmed.ncbi.nlm.nih.gov/20205104/
40) Chen WW, Li L, Yang GY, et al. Circulating FGF-21 levels in normal subjects and in newly diagnose patients with Type 2 diabetes mellitus. Experimental and Clinical Endocrinology & Diabetes, 2008; 116: 65-68. https://pubmed.ncbi.nlm.nih.gov/17926232/
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