Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2023

Open Access 01-12-2023 | Mixed Connective Tissue Disease | Research

Association of red cell distribution width with pulmonary arterial hypertension in patients with mixed connective tissue disease

Authors: Yansheng Jin, Guanjun Guo, Chun Wang, Bo Jiang

Published in: BMC Pulmonary Medicine | Issue 1/2023

Login to get access

Abstract

Background

Pulmonary arterial hypertension (PAH) is a severe complication of mixed connective tissue disease (MCTD) and contributes to increased morbidity and mortality. Still, the demographic characteristics and risk factors of PAH in MCTD remain poorly understood. This study explored risk factors for PAH development in MCTD.

Methods

Data from patients with MCTD and PAH hospitalized from May 2009 to December 2022 in a single center were collected and compared with patients with MCTD without PAH. The variables were analyzed by logistic regression to identify the factors associated with PAH in patients with MCTD. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of the identified factors.

Results

Finally, 119 patients with MCTD were included; 46 had PAH. The mean age at PAH onset and diagnosis was 38.9 ± 13.4 and 39.9 ± 13.7 years, respectively. The median pulmonary arterial systolic pressure (PASP) was 67.0 mmHg. The median brain natriuretic peptide (BNP) level was 180.0 pg/ml at PAH diagnosis. Red cell distribution width (RDW) (OR: 2.128; 95% confidence interval: 1.497–3.026; P < 0.001) was associated with PAH in patients with MCTD. There was a positive correlation between RDW and PASP (r = 0.716, P < 0.001). At a cutoff of 15.2%, RDW had the best sensitivity (80.4%) and specificity (82.2%) for PAH.

Conclusion

RDW may serve as a sensitive index to predict PAH in patients with MCTD.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ciang NC, Pereira N, Isenberg DA. Mixed connective tissue disease-enigma variations? Rheumatology (Oxford). 2017;56:326–33.PubMed Ciang NC, Pereira N, Isenberg DA. Mixed connective tissue disease-enigma variations? Rheumatology (Oxford). 2017;56:326–33.PubMed
2.
go back to reference Perelas A, Arrossi AV, Highland KB. Pulmonary manifestations of systemic sclerosis and mixed connective tissue disease. Clin Chest Med. 2019;40:501–18.CrossRefPubMed Perelas A, Arrossi AV, Highland KB. Pulmonary manifestations of systemic sclerosis and mixed connective tissue disease. Clin Chest Med. 2019;40:501–18.CrossRefPubMed
3.
go back to reference Niklas K, Niklas A, Mularek-Kubzdela T, Puszczewicz M. Prevalence of pulmonary hypertension in patients with systemic sclerosis and mixed connective tissue disease. Med (Baltim). 2018;97:e11437.CrossRef Niklas K, Niklas A, Mularek-Kubzdela T, Puszczewicz M. Prevalence of pulmonary hypertension in patients with systemic sclerosis and mixed connective tissue disease. Med (Baltim). 2018;97:e11437.CrossRef
4.
go back to reference Skride A, Sablinskis K, Avidan Y, Rudzitis A, Lejnieks A. Pulmonary arterial hypertension associated with connective tissue disease: insights from latvian PAH registry. Eur J Intern Med. 2017;40:e13–4.CrossRefPubMed Skride A, Sablinskis K, Avidan Y, Rudzitis A, Lejnieks A. Pulmonary arterial hypertension associated with connective tissue disease: insights from latvian PAH registry. Eur J Intern Med. 2017;40:e13–4.CrossRefPubMed
5.
go back to reference Liu J, Wang W, Wang L, Qi XM, Sha YH, Yang T. 3-Bromopyruvate alleviates the development of monocrotaline-induced rat pulmonary arterial hypertension by decreasing aerobic glycolysis, inducing apoptosis, and suppressing inflammation. Chin Med J (Engl). 2020;133:49–60.CrossRefPubMed Liu J, Wang W, Wang L, Qi XM, Sha YH, Yang T. 3-Bromopyruvate alleviates the development of monocrotaline-induced rat pulmonary arterial hypertension by decreasing aerobic glycolysis, inducing apoptosis, and suppressing inflammation. Chin Med J (Engl). 2020;133:49–60.CrossRefPubMed
6.
go back to reference Kasukawa R, Kanno T, Takeda I. [Mixed connective tissue disease]. Ryoikibetsu Shokogun Shirizu 2000:396–9. Kasukawa R, Kanno T, Takeda I. [Mixed connective tissue disease]. Ryoikibetsu Shokogun Shirizu 2000:396–9.
7.
go back to reference Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43:3618–731.CrossRefPubMed Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43:3618–731.CrossRefPubMed
8.
go back to reference Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of Pulmonary Hypertension. Rev Esp Cardiol (Engl Ed). 2016;69:177.CrossRefPubMed Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of Pulmonary Hypertension. Rev Esp Cardiol (Engl Ed). 2016;69:177.CrossRefPubMed
9.
go back to reference Reiseter S, Gunnarsson R, Corander J, Haydon J, Lund MB, Aalokken TM, Taraldsrud E, Hetlevik SO, Molberg O. Disease evolution in mixed connective tissue disease: results from a long-term nationwide prospective cohort study. Arthritis Res Ther. 2017;19:284.CrossRefPubMedCentralPubMed Reiseter S, Gunnarsson R, Corander J, Haydon J, Lund MB, Aalokken TM, Taraldsrud E, Hetlevik SO, Molberg O. Disease evolution in mixed connective tissue disease: results from a long-term nationwide prospective cohort study. Arthritis Res Ther. 2017;19:284.CrossRefPubMedCentralPubMed
10.
go back to reference Yang X, Mardekian J, Sanders KN, Mychaskiw MA, Thomas J. 3rd: prevalence of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review of the literature. Clin Rheumatol. 2013;32:1519–31.CrossRefPubMedCentralPubMed Yang X, Mardekian J, Sanders KN, Mychaskiw MA, Thomas J. 3rd: prevalence of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review of the literature. Clin Rheumatol. 2013;32:1519–31.CrossRefPubMedCentralPubMed
11.
go back to reference Gaine S, Chin K, Coghlan G, Channick R, Di Scala L, Galiè N, Ghofrani HA, Lang IM, McLaughlin V, Preiss R, et al. Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension. Eur Respir J. 2017;50:1602493.CrossRefPubMedCentral Gaine S, Chin K, Coghlan G, Channick R, Di Scala L, Galiè N, Ghofrani HA, Lang IM, McLaughlin V, Preiss R, et al. Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension. Eur Respir J. 2017;50:1602493.CrossRefPubMedCentral
12.
go back to reference Liu Z, Yang X, Tian Z, Qian J, Wang Q, Zhao J, Huang C, Liu Y, Guo X, Wang H, et al. The prognosis of pulmonary arterial hypertension associated with primary Sjögren’s syndrome: a cohort study. Lupus. 2018;27:1072–80.CrossRef Liu Z, Yang X, Tian Z, Qian J, Wang Q, Zhao J, Huang C, Liu Y, Guo X, Wang H, et al. The prognosis of pulmonary arterial hypertension associated with primary Sjögren’s syndrome: a cohort study. Lupus. 2018;27:1072–80.CrossRef
13.
go back to reference Iudici M, Codullo V, Giuggioli D, Riccieri V, Cuomo G, Breda S, Manfredi A, Iannace N, D’Alto M, Ghio S, et al. Pulmonary hypertension in systemic sclerosis: prevalence, incidence and predictive factors in a large multicentric italian cohort. Clin Exp Rheumatol. 2013;31:31–6. Iudici M, Codullo V, Giuggioli D, Riccieri V, Cuomo G, Breda S, Manfredi A, Iannace N, D’Alto M, Ghio S, et al. Pulmonary hypertension in systemic sclerosis: prevalence, incidence and predictive factors in a large multicentric italian cohort. Clin Exp Rheumatol. 2013;31:31–6.
14.
go back to reference Greiner S, Jud A, Aurich M, Hess A, Hilbel T, Hardt S, Katus HA, Mereles D. Reliability of noninvasive assessment of systolic pulmonary artery pressure by Doppler echocardiography compared to right heart catheterization: analysis in a large patient population. J Am Heart Assoc. 2014;3:e001103.CrossRefPubMedCentralPubMed Greiner S, Jud A, Aurich M, Hess A, Hilbel T, Hardt S, Katus HA, Mereles D. Reliability of noninvasive assessment of systolic pulmonary artery pressure by Doppler echocardiography compared to right heart catheterization: analysis in a large patient population. J Am Heart Assoc. 2014;3:e001103.CrossRefPubMedCentralPubMed
15.
go back to reference Zhang N, Zhao Y, Wang H, Sun W, Chen M, Fan Q, Yang Z, Wei W. Characteristics and risk factors for pulmonary arterial hypertension associated with primary Sjögren’s syndrome: 15 new cases from a single center. Int J Rheum Dis. 2019;22:1775–81.CrossRefPubMed Zhang N, Zhao Y, Wang H, Sun W, Chen M, Fan Q, Yang Z, Wei W. Characteristics and risk factors for pulmonary arterial hypertension associated with primary Sjögren’s syndrome: 15 new cases from a single center. Int J Rheum Dis. 2019;22:1775–81.CrossRefPubMed
16.
go back to reference Huang C, Li M, Liu Y, Wang Q, Guo X, Zhao J, Lai J, Tian Z, Zhao Y, Zeng X. Baseline characteristics and risk factors of pulmonary arterial hypertension in systemic Lupus Erythematosus Patients. Med (Baltim). 2016;95:e2761.CrossRef Huang C, Li M, Liu Y, Wang Q, Guo X, Zhao J, Lai J, Tian Z, Zhao Y, Zeng X. Baseline characteristics and risk factors of pulmonary arterial hypertension in systemic Lupus Erythematosus Patients. Med (Baltim). 2016;95:e2761.CrossRef
17.
go back to reference Foris V, Kovacs G, Tscherner M, Olschewski A, Olschewski H. Biomarkers in pulmonary hypertension: what do we know? Chest. 2013;144:274–83.CrossRefPubMed Foris V, Kovacs G, Tscherner M, Olschewski A, Olschewski H. Biomarkers in pulmonary hypertension: what do we know? Chest. 2013;144:274–83.CrossRefPubMed
18.
go back to reference Nagaya N, Nishikimi T, Uematsu M, Satoh T, Kyotani S, Sakamaki F, Kakishita M, Fukushima K, Okano Y, Nakanishi N, et al. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation. 2000;102:865–70.CrossRefPubMed Nagaya N, Nishikimi T, Uematsu M, Satoh T, Kyotani S, Sakamaki F, Kakishita M, Fukushima K, Okano Y, Nakanishi N, et al. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation. 2000;102:865–70.CrossRefPubMed
19.
go back to reference Voelkel MA, Wynne KM, Badesch DB, Groves BM, Voelkel NF. Hyperuricemia in severe pulmonary hypertension. Chest. 2000;117:19–24.CrossRefPubMed Voelkel MA, Wynne KM, Badesch DB, Groves BM, Voelkel NF. Hyperuricemia in severe pulmonary hypertension. Chest. 2000;117:19–24.CrossRefPubMed
20.
go back to reference Marvisi M, Balzarini L, Mancini C, Mouzakiti P. Thyroid gland and pulmonary hypertension. What’s the link? Panminerva Med. 2013;55:93–7.PubMed Marvisi M, Balzarini L, Mancini C, Mouzakiti P. Thyroid gland and pulmonary hypertension. What’s the link? Panminerva Med. 2013;55:93–7.PubMed
21.
go back to reference Sobanski V, Giovannelli J, Lynch BM, Schreiber BE, Nihtyanova SI, Harvey J, Handler CE, Denton CP, Coghlan JG. Characteristics and survival of Anti-U1 RNP antibody-positive patients with connective tissue Disease-Associated Pulmonary arterial hypertension. Arthritis Rheumatol. 2016;68:484–93.CrossRefPubMed Sobanski V, Giovannelli J, Lynch BM, Schreiber BE, Nihtyanova SI, Harvey J, Handler CE, Denton CP, Coghlan JG. Characteristics and survival of Anti-U1 RNP antibody-positive patients with connective tissue Disease-Associated Pulmonary arterial hypertension. Arthritis Rheumatol. 2016;68:484–93.CrossRefPubMed
22.
go back to reference Ju XF, Wang F, Wang L, Wu X, Jiang TT, You DL, Yang BH, Xia JJ, Hu SY. Dynamic change of red cell distribution width levels in prediction of Hospital Mortality in Chinese Elderly patients with septic shock. Chin Med J (Engl). 2017;130:1189–95.CrossRefPubMed Ju XF, Wang F, Wang L, Wu X, Jiang TT, You DL, Yang BH, Xia JJ, Hu SY. Dynamic change of red cell distribution width levels in prediction of Hospital Mortality in Chinese Elderly patients with septic shock. Chin Med J (Engl). 2017;130:1189–95.CrossRefPubMed
23.
go back to reference Bellan M, Giubertoni A, Piccinino C, Dimagli A, Grimoldi F, Sguazzotti M, Burlone ME, Smirne C, Sola D, Marino P, et al. Red cell distribution width and platelet count as biomarkers of pulmonary arterial hypertension in patients with connective tissue Disorders. Dis Markers. 2019;2019:4981982.CrossRefPubMedCentralPubMed Bellan M, Giubertoni A, Piccinino C, Dimagli A, Grimoldi F, Sguazzotti M, Burlone ME, Smirne C, Sola D, Marino P, et al. Red cell distribution width and platelet count as biomarkers of pulmonary arterial hypertension in patients with connective tissue Disorders. Dis Markers. 2019;2019:4981982.CrossRefPubMedCentralPubMed
24.
go back to reference Hui M, Zhao J, Tian Z, Wang J, Qian J, Yang X, Wang Q, Li M, Zhao Y, Zeng X. Red blood cell distribution width as a potential predictor of survival of pulmonary arterial hypertension associated with primary Sjogren’s syndrome: a retrospective cohort study. Clin Rheumatol. 2019;38:477–85.CrossRefPubMed Hui M, Zhao J, Tian Z, Wang J, Qian J, Yang X, Wang Q, Li M, Zhao Y, Zeng X. Red blood cell distribution width as a potential predictor of survival of pulmonary arterial hypertension associated with primary Sjogren’s syndrome: a retrospective cohort study. Clin Rheumatol. 2019;38:477–85.CrossRefPubMed
25.
go back to reference Smukowska-Gorynia A, Tomaszewska I, Malaczynska-Rajpold K, Marcinkowska J, Komosa A, Janus M, Olasinska-Wisniewska A, Slawek S, Araszkiewicz A, Jankiewicz S, Mularek-Kubzdela T. Red blood cells distribution width as a potential prognostic biomarker in patients with Pulmonary arterial hypertension and chronic Thromboembolic Pulmonary Hypertension. Heart Lung Circ. 2018;27:842–8.CrossRefPubMed Smukowska-Gorynia A, Tomaszewska I, Malaczynska-Rajpold K, Marcinkowska J, Komosa A, Janus M, Olasinska-Wisniewska A, Slawek S, Araszkiewicz A, Jankiewicz S, Mularek-Kubzdela T. Red blood cells distribution width as a potential prognostic biomarker in patients with Pulmonary arterial hypertension and chronic Thromboembolic Pulmonary Hypertension. Heart Lung Circ. 2018;27:842–8.CrossRefPubMed
26.
go back to reference Hampole CV, Mehrotra AK, Thenappan T, Gomberg-Maitland M, Shah SJ. Usefulness of red cell distribution width as a prognostic marker in pulmonary hypertension. Am J Cardiol. 2009;104:868–72.CrossRefPubMed Hampole CV, Mehrotra AK, Thenappan T, Gomberg-Maitland M, Shah SJ. Usefulness of red cell distribution width as a prognostic marker in pulmonary hypertension. Am J Cardiol. 2009;104:868–72.CrossRefPubMed
27.
go back to reference Xi Q, Liu Z, Zhao Z, Luo Q. Red blood cell distribution width predicts responsiveness of acute pulmonary vasodilator testing in patients with idiopathic pulmonary arterial hypertension. Clin Chim Acta. 2015;446:272–6.CrossRefPubMed Xi Q, Liu Z, Zhao Z, Luo Q. Red blood cell distribution width predicts responsiveness of acute pulmonary vasodilator testing in patients with idiopathic pulmonary arterial hypertension. Clin Chim Acta. 2015;446:272–6.CrossRefPubMed
28.
go back to reference Xia YK, Tu SH, Hu YH, Wang Y, Chen Z, Day HT, Ross K. Pulmonary hypertension in systemic lupus erythematosus: a systematic review and analysis of 642 cases in chinese population. Rheumatol Int. 2013;33:1211–7.CrossRefPubMed Xia YK, Tu SH, Hu YH, Wang Y, Chen Z, Day HT, Ross K. Pulmonary hypertension in systemic lupus erythematosus: a systematic review and analysis of 642 cases in chinese population. Rheumatol Int. 2013;33:1211–7.CrossRefPubMed
29.
go back to reference Zuk M, Migdal A, Dominczak J, Brzezinska-Rajszys G. Usefulness of Red Cell Width distribution (RDW) in the Assessment of Children with Pulmonary arterial hypertension (PAH). Pediatr Cardiol. 2019;40:820–6.CrossRefPubMedCentralPubMed Zuk M, Migdal A, Dominczak J, Brzezinska-Rajszys G. Usefulness of Red Cell Width distribution (RDW) in the Assessment of Children with Pulmonary arterial hypertension (PAH). Pediatr Cardiol. 2019;40:820–6.CrossRefPubMedCentralPubMed
30.
go back to reference Ozsu S, Abul Y, Gulsoy A, Bulbul Y, Yaman S, Ozlu T. Red cell distribution width in patients with obstructive sleep apnea syndrome. Lung. 2012;190:319–26.CrossRefPubMed Ozsu S, Abul Y, Gulsoy A, Bulbul Y, Yaman S, Ozlu T. Red cell distribution width in patients with obstructive sleep apnea syndrome. Lung. 2012;190:319–26.CrossRefPubMed
31.
go back to reference Inuzuka R, Abe J. Red blood cell distribution width as a link between ineffective erythropoiesis and chronic inflammation in heart failure. Circ J. 2015;79:974–5.CrossRefPubMed Inuzuka R, Abe J. Red blood cell distribution width as a link between ineffective erythropoiesis and chronic inflammation in heart failure. Circ J. 2015;79:974–5.CrossRefPubMed
32.
go back to reference Yan S, Li M, Wang H, Yang X, Zhao J, Wang Q, Liu Y, Lai J, Tian Z, Song H, et al. Characteristics and risk factors of pulmonary arterial hypertension in patients with primary Sjögren’s syndrome. Int J Rheum Dis. 2018;21:1068–75.CrossRefPubMed Yan S, Li M, Wang H, Yang X, Zhao J, Wang Q, Liu Y, Lai J, Tian Z, Song H, et al. Characteristics and risk factors of pulmonary arterial hypertension in patients with primary Sjögren’s syndrome. Int J Rheum Dis. 2018;21:1068–75.CrossRefPubMed
33.
go back to reference Pi H, Rayner SG, Ralph DD, Nolley S, Barros LM, Steinberg ZL, Leary PJ. Thyroid-stimulating hormone and mortality in pulmonary arterial hypertension. BMJ Open Respir Res. 2022;9:e001348.CrossRefPubMedCentral Pi H, Rayner SG, Ralph DD, Nolley S, Barros LM, Steinberg ZL, Leary PJ. Thyroid-stimulating hormone and mortality in pulmonary arterial hypertension. BMJ Open Respir Res. 2022;9:e001348.CrossRefPubMedCentral
34.
go back to reference Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344:501–9.CrossRef Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344:501–9.CrossRef
35.
go back to reference Rosenkranz S, Howard LS, Gomberg-Maitland M, Hoeper MM. Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart failure. Circulation. 2020;141:678–93.CrossRefPubMed Rosenkranz S, Howard LS, Gomberg-Maitland M, Hoeper MM. Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart failure. Circulation. 2020;141:678–93.CrossRefPubMed
Metadata
Title
Association of red cell distribution width with pulmonary arterial hypertension in patients with mixed connective tissue disease
Authors
Yansheng Jin
Guanjun Guo
Chun Wang
Bo Jiang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2023
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-023-02597-z

Other articles of this Issue 1/2023

BMC Pulmonary Medicine 1/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.