Skip to main content
Log in

Association of Plasma Connective Tissue Growth Factor Levels with Hyperthyroid Heart Disease

  • Published:
Current Medical Science Aims and scope Submit manuscript

Summary

Hyperthyroid heart disease (HHD) is one of the most severe complications of overt hyperthyroidism and increases the risk of mortality in affected patients. Early identification of patients at a higher risk of developing HHD can improve clinical outcomes through active surveillance and management. Connective tissue growth factor (CTGF), a secreted extracellular protein, plays a significant role in cardiac remodeling and dysfunction. We aimed to investigate the association between plasma CTGF level and the risk of HHD in this study. A total of 142 overt hyperthyroid patients without HHD and 99 patients with HHD were included. The plasma CTGF levels were measured using ELISA kits. Routine clinical medical data and echocardiography parameters were recorded for analysis. The plasma CTGF level was significantly higher in patients with HHD than in those without HHD (P=0.002). The plasma CTGF level was positively correlated with free triiodothyronin, tryrotropin receptor antibody, troponin I and lactate dehydrogenase levels and the left atrium diameters, right atrium diameters, and right ventricular end-diastolic diameters (all P<0.05). Logistic regression analysis showed that quartiles 3 and 4 of plasma CTGF levels were significantly associated with the increased risk of HHD (crude OR: 2.529; 95% CI: 1.188–5.387). However, after adjustment for the potentially confounding variables, quartile 4 alone was significantly associated with the higher risk of HHD relative to quartile 1. Hyperthyroid patients with HHD display higher plasma CTGF levels. Furthermore, CTGF is an independent risk factor for HHD. Therefore, the plasma CTGF level may be a potential biomarker for the risk of HHD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Taylor PN, Albrecht D, Scholz A, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol, 2018,14(5): 301–316

    Article  Google Scholar 

  2. Brandt F, Thvilum M, Almind D, et al. Morbidity before and after the diagnosis of hyperthyroidism: a nationwide register-based study. PLoS One, 2013,8(6):e66711

    Article  CAS  Google Scholar 

  3. Brandt F, Green A, Hegedus L, et al. A critical review and meta-analysis of the association between overt hyperthyroidism and mortality. Eur J Endocrinol, 2011,165(4):491–497

    Article  CAS  Google Scholar 

  4. Osuna PM, Udovcic M, Sharma MD. Hyperthyroidism and the Heart. Methodist Debakey Cardiovasc J, 2017, 13(2):60–63

    Article  Google Scholar 

  5. Jabbar A, Pingitore A, Pearce SH, et al. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol, 2017,14(1):39–55

    Article  CAS  Google Scholar 

  6. Siu CW, Yeung CY, Lau CP, et al. Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism. Heart, 2007,93(4):483–487

    Article  Google Scholar 

  7. Dillmann W. Cardiac hypertrophy and thyroid hormone signaling. Heart Fail Rev, 2010,15(2):125–132

    Article  CAS  Google Scholar 

  8. Chen MM, Lam A, Abraham JA, et al. CTGF expression is induced by TGF- beta in cardiac fibroblasts and cardiac myocytes: a potential role in heart fibrosis. J Mol Cell Cardiol, 2000,32(10):1805–1819

    Article  CAS  Google Scholar 

  9. Ahmed MS, Oie E, Vinge LE, et al. Connective tissue growth factor—a novel mediator of angiotensin II-stimulated cardiac fibroblast activation in heart failure in rats. J Mol Cell Cardiol, 2004,36(3):393–404

    Article  CAS  Google Scholar 

  10. Messaoudi S, Gravez B, Tarjus A, et al. Aldosteronespecific activation of cardiomyocyte mineralocorticoid receptor in vivo. Hypertension (Dallas, Tex: 1979), 2013, 61(2):361–367

    Article  CAS  Google Scholar 

  11. Recchia AG, Filice E, Pellegrino D, et al. Endothelin-1 induces connective tissue growth factor expression in cardiomyocytes. J Mol Cell Cardiol, 2009,46(3):352–359

    Article  CAS  Google Scholar 

  12. Wang X, McLennan SV, Allen TJ, et al. Adverse effects of high glucose and free fatty acid on cardiomyocytes are mediated by connective tissue growth factor. Am J Physiol Cell Physiol, 2009,297(6):C1490–1500

    Article  CAS  Google Scholar 

  13. Chi H, Feng H, Shang X, et al. Circulating Connective Tissue Growth Factor Is Associated with Diastolic Dysfunction in Patients with Diastolic Heart Failure. Cardiology, 2019,143(3–4):77–84

    Article  CAS  Google Scholar 

  14. Koitabashi N, Arai M, Niwano K, et al. Plasma connective tissue growth factor is a novel potential biomarker of cardiac dysfunction in patients with chronic heart failure. Eur J Heart Fail, 2008,10(4):373–379

    Article  CAS  Google Scholar 

  15. Tan CY, Wong JX, Chan PS, et al. Yin Yang 1 Suppresses Dilated Cardiomyopathy and Cardiac Fibrosis Through Regulation of Bmp7 and Ctgf. Circ Res, 2019,125(9):834–846

    Article  CAS  Google Scholar 

  16. Koshman YE, Sternlicht MD, Kim T, et al. Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy. J Mol Cell Cardiol, 2015,89(Pt B):214–222

    Article  CAS  Google Scholar 

  17. Hayata N, Fujio Y, Yamamoto Y, et al. Connective tissue growth factor induces cardiac hypertrophy through Akt signaling. Biochem Biophys Res Commun, 2008,370(2):274–278

    Article  CAS  Google Scholar 

  18. Panek AN, Posch MG, Alenina N, et al. Connective tissue growth factor overexpression in cardiomyocytes promotes cardiac hypertrophy and protection against pressure overload. PLoS One, 2009,4(8):e6743

    Article  Google Scholar 

  19. Hunt KJ, Jaffa MA, Garrett SM, et al. Plasma Connective Tissue Growth Factor (CTGF/CCN2) Levels Predict Myocardial Infarction in the Veterans Affairs Diabetes Trial (VADT) Cohort. Diabetes Care, 2018,41(4):840–846

    Article  CAS  Google Scholar 

  20. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid, 2016,26(10):1343–1421

    Article  Google Scholar 

  21. Zhang X, Chen L, Sheng J, et al. The Association of Autoantibodies in Hyperthyroid Heart Disease Combined with Pulmonary Hypertension. Int J Endocrinol, 2019,2019:9325289

    PubMed  PubMed Central  Google Scholar 

  22. Wang Q, Li C, Di S, et al. Clinical efficacy and safety of traditional Chinese patent medicine for hyperthyroid heart disease: study protocol for a systematic review and meta-analysis. Medicine (Baltimore), 2018,97(45):e13076

    Article  Google Scholar 

  23. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr, 2015,28(1):1–39 e14

    Article  Google Scholar 

  24. Jun JI, Lau LF. Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat Rev Drug Discov, 2011,10(12):945–963

    Article  CAS  Google Scholar 

  25. Vargas-Uricoechea H, Bonelo-Perdomo A, Sierra-Torres CH. Effects of thyroid hormones on the heart. Clin Investig Arterioscler, 2014,26(6):296–309

    PubMed  Google Scholar 

  26. Carneiro-Ramos MS, Diniz GP, Nadu AP, et al. Blockage of angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation. Basic Res Cardiol, 2010,105(3):325–335

    Article  CAS  Google Scholar 

  27. Lipson KE, Wong C, Teng Y, et al. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair, 2012,5(Suppl 1):S24

    Article  Google Scholar 

  28. Chi H, Feng H, Shang X, et al. Circulating Connective Tissue Growth Factor Is Associated with Diastolic Dysfunction in Patients with Diastolic Heart Failure. Cardiology, 2019,143(3–4):77–84

    Article  CAS  Google Scholar 

  29. Huang YM, Chang PC, Wu SB, et al. Expression and clinical significance of connective tissue growth factor (CTGF) in Graves’ ophthalmopathy. Br J Ophthalmol, 2017,101(5):676–680

    Article  Google Scholar 

  30. Chen JQ, Guo YS, Chen Q, et al. TGFbeta1 and HGF regulate CTGF expression in human atrial fibroblasts and are involved in atrial remodelling in patients with rheumatic heart disease. J Cell Mol Med, 2019,23(4):3032–3039

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Lin-fang Wang or Yu-ming Li.

Additional information

Conflict of Interest Statement

All authors declare that they have no conflicts of interest.

This study was supported by Natural Science Foundation of Hubei Province from the Science and Technology Department of Hubei Province, China (No. 2013CFB091).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, H., Zeng, Rl., Liao, Yf. et al. Association of Plasma Connective Tissue Growth Factor Levels with Hyperthyroid Heart Disease. CURR MED SCI 41, 348–355 (2021). https://doi.org/10.1007/s11596-021-2354-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-021-2354-x

Key words

Navigation