Prognostic value of serum cystatin C in patients with congenital heart disease-associated pulmonary arterial hypertension_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHU Feng ¹ , AIKEBAI Aisan ¹ , TUNIKE Maheshati ¹ , TIAN Ren ¹ , LI Yunxia ¹ , YUAN Teng ¹ ,  CHEN You ²

1. The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P. R. China;
2. Heart Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P. R. China;

Corresponding author：

CHEN You, Email: donny666@sina.com

Keywords：

Congenital heart disease; pulmonary arterial hypertension; cystatin C; all-cause death; biomarker

DOI：

10.7507/1007-4848.202103009

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Objective To explore the prognostic value of serum cystatin C (Cys C) in patients with congenital heart disease-associated pulmonary arterial hypertension (PAH-CHD).Methods A retrospective cohort study was conducted on adult PAH-CHD patients who were hospitalized for the first time in the First Affiliated Hospital of Xinjiang Medical University from January 2010 to January 2020. The serum Cys C and other related data of patients were collected. The median follow-up time was 57 months. The main end event was all-cause death. According to the prognosis, the patients were divided into a survival group and a death group. Cox regression was used to analyze the risk factors for all-cause death in patients with PAH-CHD.Results A total of 456 patients were enrolled, including 160 males and 296 females, aged 38.99±14.72 years. The baseline data showed that there were statistical differences in resting heart rate, serum Cys C, creatinine, NT-proB-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), high-sensitivity C reactive protein (hs-CRP), New York Heart Association (NYHA) cardiac function classification and serum potassium between the survival group and the death group. Univariate Cox regression analysis showed that serum Cys C, NT-proBNP, hs-cTnT, creatinine and NYHA cardiac function classification were related risk factors for all-cause death in patients with PAH-CHD. Multivariate Cox regression analysis showed that serum Cys C (HR=3.820, 95%CI 2.053-7.108, P<0.001), NYHA grade Ⅲ (HR=2.234, 95%CI 1.316-3.521, P=0.010), NYHA grade Ⅳ (HR=4.037, 95%CI 1.899-7.810, P=0.002) and NT-proBNP (HR=1.026, 95%CI 1.013-1.039, P<0.001) were independent risk factors for all-cause death in patients with PAH-CHD and had a good predictive value.Conclusion As a new cardiac marker, serum Cys C can predict all-cause death in patients with PAH-CHD and is an independent risk factor.

Citation： ZHU Feng, AIKEBAI Aisan, TUNIKE Maheshati, TIAN Ren, LI Yunxia, YUAN Teng, CHEN You. Prognostic value of serum cystatin C in patients with congenital heart disease-associated pulmonary arterial hypertension. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(2): 273-279. doi: 10.7507/1007-4848.202103009 Copy

1.	中华医学会心血管病学分会肺血管病学组中华心血管病杂志编辑委员会. 中国肺高血压诊断和治疗指南 2018. 中华心血管病杂志, 2018, 46(12): 933-964.
2.	Pascall E, Tulloh RM. Pulmonary hypertension in congenital heart disease. Future Cardiol, 2018, 14(4): 343-353.
3.	Lim Y, Low TT, Chan SP, et al. Pulmonary arterial hypertension in a multi-ethnic Asian population: Characteristics, survival and mortality predictors from a 14-year follow-up study. Respirology, 2019, 24(2): 162-170.
4.	Schuuring MJ, van Riel AC, Vis JC, et al. New predictors of mortality in adults with congenital heart disease and pulmonary hypertension: Midterm outcome of a prospective study. Int J Cardiol, 2015, 181: 270-276.
5.	Salamanca-Zarzuela B, Morales-Luego F, Alcalde-Martin C, et al. Psychomotor development in patients with severe congenital heart disease. Rev Neurol, 2018, 66(12): 409-414.
6.	Galiè N, Barberà JA, Frost AE, et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med, 2015, 373(9): 834-844.
7.	Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J, 2015, 46(4): 903-975.
8.	Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med, 2013, 369(10): 932-943.
9.	Luo J, Wang LP, Hu HF, et al. Cystatin C and cardiovascular or all-cause mortality risk in the general population: A meta-analysis. Clin Chim Acta, 2015, 450: 39-45.
10.	Cavigelli-Brunner A, Quandt D, Marcora S, et al. Multimodality imaging in rare congenital heart disease: Unilaterally absent proximal pulmonary artery in a newborn. Eur Heart J, 2018, 39(12): 1039-1040.
11.	Kaemmerer H, Apitz C, Brockmeier K, et al. Pulmonary hypertension in adults with congenital heart disease: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol, 2018, 272S: 79-88.
12.	中国医师学会心血管内科医师分会. 2015 年先天性心脏病相关性肺动脉高压诊治中国专家共识. 中国介入心脏病学杂志, 2015, 23(2): 61-69.
13.	Blok IM, van Riel AC, Schuuring MJ, et al. The role of cystatin C as a biomarker for prognosis in pulmonary arterial hypertension due to congenital heart disease. Int J Cardiol, 2016, 209: 242-247.
14.	Kaemmerer H, Gorenflo M, Huscher D, et al. Pulmonary hypertension in adults with congenital heart disease: Real-world data from the international COMPERA-CHD registry. J Clin Med, 2020, 9(5): 1456.
15.	徐茁原, 李强强, 张陈, 等. 先天性心脏病相关肺动脉高压患者死亡的危险因素及不同亚型的临床特点. 中华心血管病杂志, 2020, 48(4): 315-322.
16.	甘露, 郭雨鑫, 沈国军, 等. 西地那非治疗高原地区先天性心脏病合并重度肺动脉高压的疗效观察. 中国医药指南, 2018, 16(25): 40.
17.	Chen S, Tang Y, Zhou X. Cystatin C for predicting all-cause mortality and rehospitalization in patients with heart failure: A meta-analysis. Biosci Rep, 2019, 39(2): BSR20181761.
18.	Breidthardt T, Sabti Z, Ziller R, et al. Diagnostic and prognostic value of cystatin C in acute heart failure. Clin Biochem, 2017, 50(18): 1007-1013.
19.	Mebius MJ, Oostdijk NJE, Kuik SJ, et al. Amplitude-integrated electroencephalography during the first 72 h after birth in neonates diagnosed prenatally with congenital heart disease. Pediatr Res, 2018, 83(4): 798-803.
20.	Cordina R, Nasir Ahmad S, Kotchetkova I, et al. Management errors in adults with congenital heart disease: Prevalence, sources, and consequences. Eur Heart J, 2018, 39(12): 982-989.
21.	Abouk R, Grosse SD, Ailes EC, et al. Association of US State implementation of newborn screening policies for critical congenital heart disease with early infant cardiac deaths. JAMA, 2017, 318(21): 2111-2118.
22.	Díez J. Altered degradation of extracellular matrix in myocardial remodelling: The growing role of cathepsins and cystatins. Cardiovasc Res, 2010, 87(4): 591-592.
23.	Cheng XW, Obata K, Kuzuya M, et al. Elastolytic cathepsin induction/activation system exists in myocardium and is upregulated in hypertensive heart failure. Hypertension, 2006, 48(5): 979-987.
24.	Xu Y, Ding Y, Li X, et al. Cystatin C is a disease-associated protein subject to multiple regulation. Immunol Cell Biol, 2015, 93(5): 442-451.
25.	Roth TS, Aboulhosn JA. Pulmonary hypertension and congenital heart disease. Cardiol Clin, 2016, 34(3): 391-400.
26.	Deng X, Jin B, Li S, et al. Guideline implementation and early risk assessment in pulmonary arterial hypertension associated with congenital heart disease: A retrospective cohort study. Clin Respir J, 2019, 13(11): 693-699.
27.	Richter B, Koller L, Hohensinner PJ, et al. A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure. Int J Cardiol, 2013, 168(2): 1251-1257.
28.	Shlipak MG, Mattes MD, Peralta CA. Update on cystatin C: Incorporation into clinical practice. Am J Kidney Dis, 2013, 62(3): 595-603.

1. 中华医学会心血管病学分会肺血管病学组中华心血管病杂志编辑委员会. 中国肺高血压诊断和治疗指南 2018. 中华心血管病杂志, 2018, 46(12): 933-964.
2. Pascall E, Tulloh RM. Pulmonary hypertension in congenital heart disease. Future Cardiol, 2018, 14(4): 343-353.
3. Lim Y, Low TT, Chan SP, et al. Pulmonary arterial hypertension in a multi-ethnic Asian population: Characteristics, survival and mortality predictors from a 14-year follow-up study. Respirology, 2019, 24(2): 162-170.
4. Schuuring MJ, van Riel AC, Vis JC, et al. New predictors of mortality in adults with congenital heart disease and pulmonary hypertension: Midterm outcome of a prospective study. Int J Cardiol, 2015, 181: 270-276.
5. Salamanca-Zarzuela B, Morales-Luego F, Alcalde-Martin C, et al. Psychomotor development in patients with severe congenital heart disease. Rev Neurol, 2018, 66(12): 409-414.
6. Galiè N, Barberà JA, Frost AE, et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med, 2015, 373(9): 834-844.
7. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J, 2015, 46(4): 903-975.
8. Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med, 2013, 369(10): 932-943.
9. Luo J, Wang LP, Hu HF, et al. Cystatin C and cardiovascular or all-cause mortality risk in the general population: A meta-analysis. Clin Chim Acta, 2015, 450: 39-45.
10. Cavigelli-Brunner A, Quandt D, Marcora S, et al. Multimodality imaging in rare congenital heart disease: Unilaterally absent proximal pulmonary artery in a newborn. Eur Heart J, 2018, 39(12): 1039-1040.
11. Kaemmerer H, Apitz C, Brockmeier K, et al. Pulmonary hypertension in adults with congenital heart disease: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol, 2018, 272S: 79-88.
12. 中国医师学会心血管内科医师分会. 2015 年先天性心脏病相关性肺动脉高压诊治中国专家共识. 中国介入心脏病学杂志, 2015, 23(2): 61-69.
13. Blok IM, van Riel AC, Schuuring MJ, et al. The role of cystatin C as a biomarker for prognosis in pulmonary arterial hypertension due to congenital heart disease. Int J Cardiol, 2016, 209: 242-247.
14. Kaemmerer H, Gorenflo M, Huscher D, et al. Pulmonary hypertension in adults with congenital heart disease: Real-world data from the international COMPERA-CHD registry. J Clin Med, 2020, 9(5): 1456.
15. 徐茁原, 李强强, 张陈, 等. 先天性心脏病相关肺动脉高压患者死亡的危险因素及不同亚型的临床特点. 中华心血管病杂志, 2020, 48(4): 315-322.
16. 甘露, 郭雨鑫, 沈国军, 等. 西地那非治疗高原地区先天性心脏病合并重度肺动脉高压的疗效观察. 中国医药指南, 2018, 16(25): 40.
17. Chen S, Tang Y, Zhou X. Cystatin C for predicting all-cause mortality and rehospitalization in patients with heart failure: A meta-analysis. Biosci Rep, 2019, 39(2): BSR20181761.
18. Breidthardt T, Sabti Z, Ziller R, et al. Diagnostic and prognostic value of cystatin C in acute heart failure. Clin Biochem, 2017, 50(18): 1007-1013.
19. Mebius MJ, Oostdijk NJE, Kuik SJ, et al. Amplitude-integrated electroencephalography during the first 72 h after birth in neonates diagnosed prenatally with congenital heart disease. Pediatr Res, 2018, 83(4): 798-803.
20. Cordina R, Nasir Ahmad S, Kotchetkova I, et al. Management errors in adults with congenital heart disease: Prevalence, sources, and consequences. Eur Heart J, 2018, 39(12): 982-989.
21. Abouk R, Grosse SD, Ailes EC, et al. Association of US State implementation of newborn screening policies for critical congenital heart disease with early infant cardiac deaths. JAMA, 2017, 318(21): 2111-2118.
22. Díez J. Altered degradation of extracellular matrix in myocardial remodelling: The growing role of cathepsins and cystatins. Cardiovasc Res, 2010, 87(4): 591-592.
23. Cheng XW, Obata K, Kuzuya M, et al. Elastolytic cathepsin induction/activation system exists in myocardium and is upregulated in hypertensive heart failure. Hypertension, 2006, 48(5): 979-987.
24. Xu Y, Ding Y, Li X, et al. Cystatin C is a disease-associated protein subject to multiple regulation. Immunol Cell Biol, 2015, 93(5): 442-451.
25. Roth TS, Aboulhosn JA. Pulmonary hypertension and congenital heart disease. Cardiol Clin, 2016, 34(3): 391-400.
26. Deng X, Jin B, Li S, et al. Guideline implementation and early risk assessment in pulmonary arterial hypertension associated with congenital heart disease: A retrospective cohort study. Clin Respir J, 2019, 13(11): 693-699.
27. Richter B, Koller L, Hohensinner PJ, et al. A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure. Int J Cardiol, 2013, 168(2): 1251-1257.
28. Shlipak MG, Mattes MD, Peralta CA. Update on cystatin C: Incorporation into clinical practice. Am J Kidney Dis, 2013, 62(3): 595-603.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Prognostic value of serum cystatin C in patients with congenital heart disease-associated pulmonary arterial hypertension

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