Fibroblast Growth Factor 21 is Associated with Widening QRS Complex and Prolonged Corrected QT Interval in Patients with Stable Angina

Overview

Journal BMC Cardiovasc Disord

Publisher Biomed Central

Specialty Cardiology & Vascular Diseases

Date 2022 Sep 30

PMID 36180826

Authors

Wei-Chin Hung

Teng-Hung Yu

Chao-Ping Wang

Chia-Chang Hsu

Yung-Chuan Lu

Ching-Ting Wei

Fu-Mei Chung

Yau-Jiunn Lee

Cheng-Ching Wu

Wei-Hua Tang

Affiliations

Soon will be listed here.

Abstract

Background: Fibroblast growth factor 21 (FGF21) is produced by cardiac cells, may acts in an autocrine manner, and was suggested to has a cardioprotective role in atherosclerosis. Wide QRS complex and heart rate-corrected QT interval (QTc interval) prolongation are associated to dangerous ventricular arrhythmias and cardiovascular disease mortality. Yet, the role of FGF21 in cardiac arrhythmia has never been studied. The aim of the study was to investigate the relationship between plasma FGF21 and the QRS duration and QTc interval in patients with stable angina.

Methods: Three hundred twenty-one consecutive stable angina patients were investigated. Plasma FGF21 was measured through ELISA, and each subject underwent 12-lead electrocardiography.

Results: FGF21 plasma levels were positively associated with the QRS duration (β = 0.190, P = 0.001) and QTc interval (β = 0.277, P < 0.0001). With increasing FGF21 tertiles, the patients had higher frequencies of wide QRS complex and prolonged QTc interval. After adjusting for patients' anthropometric parameters, the corresponding odd ratios (ORs) for wide QRS complex of the medium and high of FGF21 versus the low of FGF21 were 1.39 (95% CI 0.51-3.90) and 4.41 (95% CI 1.84-11.59), respectively, and p for trend was 0.001. Furthermore, multiple logistic regression analysis also showed the corresponding odd ratios (ORs) for prolonged QTc interval of the medium and high of FGF21 versus the low of FGF21 were 1.02 (95% CI 0.53-1.78) and 1.93 (95% CI 1.04-3.60) respectively with the p for trend of 0.037. In addition, age- and sex-adjusted FGF21 levels were positively associated with fasting glucose, HbA1c, creatinine, and adiponectin, but negatively associated with albumin, and the estimated glomerular filtration rate.

Conclusions: This study indicates that plasma FGF21 is associated with wide QRS complex and prolonged corrected QT interval in stable angina patients, further study is required to investigate the role of plasma FGF21 for the underlying pathogenesis.

References

Tang W, Wang C, Chung F, Huang L, Yu T, Hung W . Uremic retention solute indoxyl sulfate level is associated with prolonged QTc interval in early CKD patients. PLoS One. 2015; 10(3):e0119545. PMC: 4403985. DOI: 10.1371/journal.pone.0119545. View

Passman R, KADISH A . Polymorphic ventricular tachycardia, long Q-T syndrome, and torsades de pointes. Med Clin North Am. 2001; 85(2):321-41. DOI: 10.1016/s0025-7125(05)70318-7. View

Malik M, Hnatkova K, Batchvarov V, Gang Y, Smetana P, Camm A . Sample size, power calculations, and their implications for the cost of thorough studies of drug induced QT interval prolongation. Pacing Clin Electrophysiol. 2004; 27(12):1659-69. DOI: 10.1111/j.1540-8159.2004.00701.x. View

Levy D, Savage D, Garrison R, Anderson K, Kannel W, CASTELLI W . Echocardiographic criteria for left ventricular hypertrophy: the Framingham Heart Study. Am J Cardiol. 1987; 59(9):956-60. DOI: 10.1016/0002-9149(87)91133-7. View

Elffers T, de Mutsert R, Lamb H, Maan A, Macfarlane P, Willems van Dijk K . Association of metabolic syndrome and electrocardiographic markers of subclinical cardiovascular disease. Diabetol Metab Syndr. 2017; 9:40. PMC: 5441065. DOI: 10.1186/s13098-017-0238-9. View

Cuddy T, Tate R . Sudden unexpected cardiac death as a function of time since the detection of electrocardiographic and clinical risk factors in apparently healthy men: the Manitoba Follow-Up Study, 1948 to 2004. Can J Cardiol. 2006; 22(3):205-11. PMC: 2528914. DOI: 10.1016/s0828-282x(06)70897-2. View

Chow W, Xu A, Woo Y, Tso A, Cheung S, Fong C . Serum fibroblast growth factor-21 levels are associated with carotid atherosclerosis independent of established cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2013; 33(10):2454-9. DOI: 10.1161/ATVBAHA.113.301599. View

Gibbons R, Chatterjee K, Daley J, Douglas J, Fihn S, Gardin J . ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: executive summary and recommendations. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on.... Circulation. 1999; 99(21):2829-48. DOI: 10.1161/01.cir.99.21.2829. View

Lin Z, Wu Z, Yin X, Liu Y, Yan X, Lin S . Serum levels of FGF-21 are increased in coronary heart disease patients and are independently associated with adverse lipid profile. PLoS One. 2011; 5(12):e15534. PMC: 3012070. DOI: 10.1371/journal.pone.0015534. View

10.

Chou R, Huang P, Hsu C, Chang C, Leu H, Huang C . Circulating Fibroblast Growth Factor 21 is Associated with Diastolic Dysfunction in Heart Failure Patients with Preserved Ejection Fraction. Sci Rep. 2016; 6:33953. PMC: 5030655. DOI: 10.1038/srep33953. View

11.

Shen Y, Ma X, Zhou J, Pan X, Hao Y, Zhou M . Additive relationship between serum fibroblast growth factor 21 level and coronary artery disease. Cardiovasc Diabetol. 2013; 12:124. PMC: 3766150. DOI: 10.1186/1475-2840-12-124. View

12.

Devi M, Arvind T, Kumar P . ECG Changes in Smokers and Non Smokers-A Comparative Study. J Clin Diagn Res. 2013; 7(5):824-6. PMC: 3681047. DOI: 10.7860/JCDR/2013/5180.2950. View

13.

Planavila A, Redondo I, Hondares E, Vinciguerra M, Munts C, Iglesias R . Fibroblast growth factor 21 protects against cardiac hypertrophy in mice. Nat Commun. 2013; 4:2019. DOI: 10.1038/ncomms3019. View

14.

Grisanti L . Diabetes and Arrhythmias: Pathophysiology, Mechanisms and Therapeutic Outcomes. Front Physiol. 2018; 9:1669. PMC: 6275303. DOI: 10.3389/fphys.2018.01669. View

15.

Ohkubo K, Watanabe I, Okumura Y, Ashino S, Kofune M, Nagashima K . Prolonged QRS duration in lead V2 and risk of life-threatening ventricular Arrhythmia in patients with Brugada syndrome. Int Heart J. 2011; 52(2):98-102. DOI: 10.1536/ihj.52.98. View

16.

Wang N, Maggioni A, Konstam M, Zannad F, Krasa H, Burnett Jr J . Clinical implications of QRS duration in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction. JAMA. 2008; 299(22):2656-66. DOI: 10.1001/jama.299.22.2656. View

17.

Planavila A, Redondo-Angulo I, Villarroya F . FGF21 and Cardiac Physiopathology. Front Endocrinol (Lausanne). 2015; 6:133. PMC: 4553397. DOI: 10.3389/fendo.2015.00133. View

18.

. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011; 35 Suppl 1:S64-71. PMC: 3632174. DOI: 10.2337/dc12-s064. View

19.

Liu W, Huang S, Shi K, Zhao C, Chen L, Braddock M . The role of fibroblast growth factor 21 in the pathogenesis of liver disease: a novel predictor and therapeutic target. Expert Opin Ther Targets. 2014; 18(11):1305-13. DOI: 10.1517/14728222.2014.944898. View

20.

Lenart-Lipinska M, Matyjaszek-Matuszek B, Gernand W, Nowakowski A, Solski J . Serum fibroblast growth factor 21 is predictive of combined cardiovascular morbidity and mortality in patients with type 2 diabetes at a relatively short-term follow-up. Diabetes Res Clin Pract. 2013; 101(2):194-200. DOI: 10.1016/j.diabres.2013.04.010. View