Clinical Rheumatology

, Volume 38, Issue 12, pp 3619–3626 | Cite as

Simplified risk stratification for pulmonary arterial hypertension associated with connective tissue disease

  • Xiaodi Li
  • Xiaoxuan Sun
  • Yingheng Huang
  • Yuanyuan Wang
  • Xiaoman Yang
  • Jingya Wang
  • Ning Zhang
  • Lei Gu
  • Miaojia ZhangEmail author
  • Qiang WangEmail author
Original Article



To explore the long-term prognostic value of a simplified risk assessment strategy based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension (PH) guidelines in Chinese patients with connective tissue disease (CTD) associated with pulmonary arterial hypertension (PAH).


We identified 50 CTD-PAH patients diagnosed by right heart catheterization. A retrospective chart review was completed to assess their clinical presentation and laboratory test results. A simplified version of the risk stratification model proposed by the 2015 ESC/ERS PH guidelines was applied, which included the WHO functional class, the 6-minute walking distance test, N-terminal pro-B-type natriuretic peptide plasma levels, pericardial effusion, right atrial pressure (RAP), cardiac index (CI), and mixed venous oxygen saturation (SvO2). The risk grades were defined as follows: low risk = at least 3 low-risk variables and no high-risk variables; high risk = at least 2 high-risk variables, including SvO2 or CI; and intermediate risk = when the above definitions of low or high risk were not fulfilled. The study endpoint was 3-year all-cause mortality.


Twenty patients were defined as a low-risk group, while 30 were classified into a combined intermediate-high-risk group at the baseline assessment. All 20 patients in the low-risk group remained in the low-risk group at follow-up, 20 patients in the intermediate-high-risk group were downgraded to the low-risk group, and eight patients remained in the intermediate-high-risk group at the follow-up assessment. Patients in the intermediate-high-risk group exhibited higher 3-year mortality than the low-risk group at baseline (26% vs 14%, P = 0.0384). Compared with patients who remained in the intermediate-high-risk group, patients who were downgraded to the low-risk group showed lower 3-year mortality (P = 0.0281).


A simplified risk stratification model based on the 2015 ESC/ERS PH guidelines helped to identify CTD-PAH patients with poor long-term  prognosis , which was useful in evaluating the severity and treatment response of patients with CTD-PAH.

Key Point

•This study showed that the simplified version of the 2015 ESC/ERS risk stratification model could help identify Chinese CTD-PAH patients with poor prognosis at diagnosis and after treatment initiation.


Connective tissue disease Prognosis Pulmonary arterial hypertension Risk stratification 



Pulmonary arterial hypertension


Connective tissue disease


Idiopathic pulmonary arterial hypertension


European Society of Cardiology


European Respiratory Society


Pulmonary hypertension


Functional class


6-minute walking distance


N-terminal pro-B-type natriuretic peptide


Pulmonary vascular resistance


Right heart catheterization


Mean pulmonary arterial pressure


Pulmonary arterial wedge pressure


Interstitial lung disease


High-resolution computer tomography


Systematic lupus erythematosus


American Rheumatism Association


Primary Sjogren’s syndrome


Systemic sclerosis


Mixed connective tissue disease


Undifferentiated connective tissue disease


Mixed venous oxygen saturation


Cardiac index


Right atrial pressure



Thanks to  all patients involved in  this retrospective study.


This study was supported by the National Natural Science Foundation of China (NSFC) (81671615, 81701610, and 81302575), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Young Medical People Project in Jiangsu Province, and Medical Talent of Empowering Medicine through Science and Education Program.

Compliance with ethical standards

This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Nanjing Medical University and it has been performed in accordance with the ethical standard laid down in the 1964 Declaration of Helsinki.




  1. 1.
    Koh ET, Lee P, Gladman DD et al (1996) Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. Br J Rheumatol 35(10):989–993CrossRefGoogle Scholar
  2. 2.
    Condliffe R, Kiely DG, Peacock AJ, Corris PA, Gibbs JSR, Vrapi F, Das C, Elliot CA, Johnson M, DeSoyza J, Torpy C, Goldsmith K, Hodgkins D, Hughes RJ, Pepke-Zaba J, Coghlan JG (2009) Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med 179(2):151–157CrossRefGoogle Scholar
  3. 3.
    Zhang R, Dai LZ, Xie WP, Yu ZX, Wu BX, Pan L, Yuan P, Jiang X, He J, Humbert M, Jing ZC (2011) Survival of Chinese patients with pulmonary arterial hypertension in the modern treatment era. Chest. 140(2):301–309CrossRefGoogle Scholar
  4. 4.
    Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD (2012) An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 142(2):448–456CrossRefGoogle Scholar
  5. 5.
    Galie N, Humbert M, Vachiery JL et al (2016) 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 37:67–119CrossRefGoogle Scholar
  6. 6.
    Kylhammar D, Kjellström B, Hjalmarsson C, Jansson K, Nisell M, Söderberg S, Wikström G, Rådegran G (2018) A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension. Eur Heart J 39(47):4175–4181CrossRefGoogle Scholar
  7. 7.
    Hoeper MM, Kramer T, Pan Z, Eichstaedt CA, Spiesshoefer J, Benjamin N, Olsson KM, Meyer K, Vizza CD, Vonk-Noordegraaf A, Distler O, Opitz C, Gibbs JSR, Delcroix M, Ghofrani HA, Huscher D, Pittrow D, Rosenkranz S, Grünig E (2017) Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J 50:1700740CrossRefGoogle Scholar
  8. 8.
    Zhao J, Wang Q, Liu Y, Tian Z, Guo X, Wang H, Lai J, Huang C, Yang X, Li M, Zeng X (2017) Clinical characteristics and survival of pulmonary arterial hypertension associated with three major connective tissue diseases: a cohort study in China. Int J Cardiol 236:432–437CrossRefGoogle Scholar
  9. 9.
    Hao YJ, Jiang X, Zhou W, Wang Y, Gao L, Wang Y, Li GT, Hong T, Huo Y, Jing ZC, Zhang ZL (2014) Connective tissue disease-associated pulmonary arterial hypertension in Chinese patients. Eur Respir J 44(4):963–972CrossRefGoogle Scholar
  10. 10.
    Hochberg MC (2014) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725–1725CrossRefGoogle Scholar
  11. 11.
    Vitali C, Bombardieri S, Jonsson R et al (2002) Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61(6):554–558CrossRefGoogle Scholar
  12. 12.
    Hoogen FVD, Khanna D, Fransen J et al (2013) Classification criteria for systemic sclerosis: an ACR-EULAR collaborative initiative. Arthritis Rheum 65(11):2737–2747CrossRefGoogle Scholar
  13. 13.
    Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR (1972) Mixed connective tissue disease-an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 52(2):148–159CrossRefGoogle Scholar
  14. 14.
    Wensel R, Francis DP, Meyer FJ, Opitz CF, Bruch L, Halank M, Winkler J, Seyfarth HJ, Gläser S, Blumberg F, Obst A, Dandel M, Hetzer R, Ewert R (2013) Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonary arterial hypertension. Int J Cardiol 167(4):1193–1119CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Department of RheumatologyThe first affiliated hospital of Nanjing Medical UniversityNanjingChina

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