Skip to main content Accessibility help
×
Home

The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure

  • Gang Li (a1), Xueqing Song (a2), Jiyi Xia (a3), Jing Li (a4), Peng Jia (a1), Pengyuan Chen (a5), Jian Zhao (a1) and Bin Liu (a1)...

Abstract

Objective

The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure.

Methods and results

Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p<0.01). N-terminal pro-brain natriuretic peptide and left ventricular end-diastolic dimension were positively correlated with plasma N-terminal connective tissue growth factor levels (r=0.364, p=0.006; r=0.308, p=0.016), whereas there was a negative correlation between left ventricular ejection fraction and plasma N-terminal connective tissue growth factor (r=−0.353, p=0.005). Connective tissue growth factor was significantly correlated with the severity of heart failure (p<0.001). Moreover, addition of connective tissue growth factor to N-terminal pro-brain natriuretic peptide did not significantly increase area under curve for diagnosing heart failure (area under curve difference 0.031, p>0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices.

Conclusions

Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

Copyright

Corresponding author

Correspondence to: B. Liu, Department of Pediatrics, The Affiliated Hospital of Sichuan Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan, China. Tel: +86 830 3165613; Fax: +86 830 3163899; E-mail: lblyfy@126.com

References

Hide All
1. Rossano, JW, Jang, GY. Pediatric heart failure: current state and future possibilities. Korean Circ J 2015; 45: 18.
2. Fiuzat, M, O’Connor, CM, Gueyffier, F, et al. Biomarker-guided therapies in heart failure: a forum for unified strategies. J Card Fail 2013; 19: 592599.
3. Gruson, D, Ahn, SA, Rousseau, MF. Multiple biomarker strategy based on parathyroid hormone and natriuretic peptides testing for improved prognosis of chronic heart failure. Peptides 2015; 64: 2428.
4. Cohen, S, Springer, C, Avital, A, et al. Amino-terminal pro-brain-type natriuretic peptide: heart or lung disease in pediatric respiratory distress. Pediatrics 2005; 115: 13471350.
5. Nir, A, Bar-Oz, B, Perles, Z, Brooks, R, Korach, A, Rein, AJ. N-terminal pro-B-type natriuretic peptide: reference plasma levels from birth to adolescence. Elevated levels at birth and in infants and children with heart diseases. Acta Paediatr 2004; 93: 603607.
6. Nir, A, Nasser, N. Clinical value of NT-proBNP and BNP in pediatric cardiology. J Card Fail 2005; 11: S76S80.
7. Zhang, SR, Zhang, YH, Xu, Q, Qiu, HX, Chen, Q. Values of brain natriuretic peptide and N-terminal pro-brain natriuretic peptide in evaluation of cardiac function in children with CHD. Zhongguo Dang Dai Er Ke Za Zhi 2009; 11: 429432.
8. Bradham, DM, Igarashi, A, Potter, RL, Grotendorst, GR. Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10. J Cell Biol 1991; 114: 12851294.
9. Chen, L, Charrier, A, Zhou, Y, et al. Epigenetic regulation of connective tissue growth factor by MicroRNA-214 delivery in exosomes from mouse or human hepatic stellate cells. Hepatology 2014; 59: 11181129.
10. Klaassen, I, van Geest, RJ, Kuiper, EJ, van Noorden, CJ, Schlingemann, RO. The role of CTGF in diabetic retinopathy. Exp Eye Res 2015; 133: 3748.
11. Wu, CK, Wang, YC, Lee, JK, et al. Connective tissue growth factor and cardiac diastolic dysfunction: human data from the Taiwan diastolic heart failure registry and molecular basis by cellular and animal models. Eur J Heart Fail 2014; 16: 163172.
12. Dziadzio, M, Usinger, W, Leask, A, et al. N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma. QJM 2005; 98: 485492.
13. 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: 373379.
14. Bergestuen, DS, Gravning, J, Haugaa, KH, et al. Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors. BMC Cancer 2010; 10: 6.
15. Behnes, M, Brueckmann, M, Lang, S, et al. Connective tissue growth factor (CTGF/CCN2): diagnostic and prognostic value in acute heart failure. Clin Res Cardiol 2014; 103: 107116.
16. Miyazaki, O, Kurashita, S, Fukamachi, I, Endo, K, Ng, PS, Takehara, K. Subtraction method for determination of N-terminal connective tissue growth factor. Ann Clin Biochem 2010; 47: 205211.
17. Ross, RD. The Ross classification for heart failure in children after 25 years: a review and an age-stratified revision. Pediatr Cardiol 2012; 33: 12951300.
18. Lopez, L, Colan, SD, Frommelt, PC, et al. Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr 2010; 23: 465495; quiz 576–577.
19. Cicha, I, Garlichs, CD, Daniel, WG, Goppelt-Struebe, M. Activated human platelets release connective tissue growth factor. Thromb Haemost 2004; 91: 755760.
20. Kato, M, Fujisawa, T, Hashimoto, D, et al. Plasma connective tissue growth factor levels as potential biomarkers of airway obstruction in patients with asthma. Ann Allergy Asthma Immunol 2014; 113: 295300.
21. Hanley, JA, McNeil, BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 1983; 148: 839843.
22. Pencina, MJ, D’Agostino, RB Sr, D’Agostino, RB Jr, Vasan, RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008; 27: 157172; discussion 207–212.
23. Chuva de Sousa Lopes, SM, Feijen, A, Korving, J, et al. Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction. Dev Dyn 2004; 231: 542550.
24. Ahmed, MS, Øie, 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: 393404.
25. Koitabashi, N, Arai, M, Kogure, S, et al. Increased connective tissue growth factor relative to brain natriuretic peptide as a determinant of myocardial fibrosis. Hypertension 2007; 49: 11201127.
26. Tsoutsman, T, Wang, X, Garchow, K, Riser, B, Twigg, S, Semsarian, C. CCN2 plays a key role in extracellular matrix gene expression in severe hypertrophic cardiomyopathy and heart failure. J Mol Cell Cardiol 2013; 62: 164178.
27. Blom, IE, Goldschmeding, R, Leask, A. Gene regulation of connective tissue growth factor: new targets for antifibrotic therapy. Matrix Biol 2002; 21: 473482.
28. Sahin, M, Portakal, O, Karagöz, T, Hasçelik, G, Özkutlu, S. Diagnostic performance of BNP and NT-proBNP measurements in children with heart failure based on congenital heart defects and cardiomyopathies. Clin Biochem 2010; 43: 12781281.
29. Gravning, J, Ahmed, MS, von Lueder, TG, Edvardsen, T, Attramadal, H. CCN2/CTGF attenuates myocardial hypertrophy and cardiac dysfunction upon chronic pressure-overload. Int J Cardiol 2013; 168: 20492056.
30. Gravning, J, Ørn, S, Kaasbøll, OJ, et al. Myocardial connective tissue growth factor (CCN2/CTGF) attenuates left ventricular remodeling after myocardial infarction. PLoS One 2012; 7: e52120.
31. Braunwald, E. Biomarkers in heart failure. N Engl J Med 2008; 358: 21482159.
32. Hayata, N, Fujio, Y, Yamamoto, Y, et al. Connective tissue growth factor induces cardiac hypertrophy through Akt signaling. Biochem Biophys Res Commun 2008; 370: 274278.
33. Jungbauer, CG, Riedlinger, J, Block, D, et al. Panel of emerging cardiac biomarkers contributes for prognosis rather than diagnosis in chronic heart failure. Biomark Med 2014; 8: 777789.
34. Bielecka-Dabrowa, A, Gluba-Brzózka, A, Michalska-Kasiczak, M, Misztal, M, Rysz, J, Banach, M. The multi-biomarker approach for heart failure in patients with hypertension. Int J Mol Sci 2015; 16: 1071510733.

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed