The Incidence and Prevalence of Pulmonary Hypertension in the COPD Population: A Systematic Review and Meta-Analysis

Figures & data

Figure 1 Flow diagram of the systematic search and selection of studies.

Note: Numbers refer to unique records not datasets, except where otherwise indicated.

Table 1 Characteristics of Studies Reporting the Prevalence of COPD-Related PH

Study	Country	Enrolment Time	Total	Gender (M/F)	Mean Age	Sample Source	Sample Type	Diagnostic Methods for PH	Prevalence
Acharya et al 2018^Citation46	India	2012–2014	50	NA	61.14±10.33	NA	Stable	TTE	54.00%
Aksu et al 2013^Citation47	Turkey	2008–2009	89	77/12	60.6±8.5	NA	Stable	TTE	23.60%
Alkukhun et al 2014^Citation48	America	2004–2011	92	31/61	55.1	Lung transplants	NA	RHC	32.60%
Andersen et al 2012^Citation15	Danish	1991–2010	409	140/216	54.01	Lung transplants	Stable	RHC	48.66%
Blanco et al 2019^Citation49	Spain	NA	3105	1612/1493	59.5	Lung transplants	NA	RHC	54.00%
Buklioska et al 2019^Citation50	Skopje	2018–2018	60	52/8	NA	NA	NA	TTE	33.33%
Chaouat et al 2009^Citation51	France	NA	183	160/23	67.0–79.0	NA	Stable	TTE	21.90%
Chen et al 2015^Citation52	China	2013–2014	221	175/46	69±10	Inpatients		TTE	25.34%
Fayngersh et al 2011^Citation53	America	2002–2008	174	155/19	40–80	NA	Stable	TTE	37.36%
Freixa et al 2012^Citation54	Spain	2004–2006	342	318/24	67.9±8.6	Inpatients	AECOPD	TTE	19.00%
Gartman et al 2012^Citation55	America	2008–2010	142	84/58	59	Lung transplants	NA	RHC	63.38%
Gupta et al 2018^Citation56	India	2015–2016	109	72/27	58.04	NA	NA	TTE	62.40%
Halvani et al 2019^Citation57	Islam	NA	142	NA	67.5–70.8	Outpatients	Stable	TTE	63.38%
Hayes et al 2017^Citation58	America	2005–2013	86	31/55	60.86	Outpatients	Stable	TTE	63.00%
Hilde et al 2016^Citation59	Norway	NA	100	49/51	63±7	NA	Stable	RHC	26.00%
Jethani et al 2016^Citation60	India	NA	50	49/1	35–80	NA	NA	TTE	48.00%
Kwon et al 2010^Citation61	Korea	2009	108	82/26	71.79	NA	NA	TTE	53.70%
Malinovschi et al 2014^Citation62	Italy	2011–2012	276	186/90	67.76	Inpatients	Stable	RHC	47.80%
Matsuyama et al 2001^Citation63	Japan	NA	65	NA	65.64	Inpatients	NA	RHC	32.31%
Mohamed et al 2016^Citation64	Netherlands	2004–2014	65	33/32	59.34	Lung transplants	NA	RHC	58.46%
Mohamed et al 2019^Citation65	Egypt	2017–2018	228	NA	63.30±9.22	Outpatients	Stable	TTE	63.00%
Nakahara et al 2016^Citation66	Japan	2007–2013	503	NA	69.9±6.8	Inpatients	Stable	RHC	16.70%
Nakayama et al 2020^Citation67	Japan	2010–2012	105	57/48	68.14	NA	NA	TTE	60.00%
Nathan et al 2012^Citation68	America	2005–2018	6572	3252/3320	60.4±6.3	Lung transplants	NA	RHC	52.40%
Portillo et al 2015^Citation69	Spain	NA	139	134/5	63±8	NA	Stable	RHC	18.00%
Sertogullarindan et al 2012^Citation70	Turkey	2000–2010	600	336/264	67±10	Inpatients	Stable	TTE	54.17%
Seyhan et al 2013^Citation71	Turkey	2007–2009	270	207/63	61±7.3	NA	Stable	TTE	48.00%
Shabrawy et al 2017^Citation72	Egypt	2012–2014	252	163/89	58.46	NA	AECOPD	TTE	64.80%
Shin et al 2014^Citation73	America	1998–2012	148	118/30	63.39	NA	Stable	RHC	39.00%
Sims et al 2009^Citation74	America	1991–2003	362	NA	55.95	Lung transplants	NA	RHC	23.00%
Skjorten et al 2013^Citation75	Norway	2006	96	48/48	63.47	Outpatients	Stable	RHC	26.00%
Sridhara et al 2020^Citation76	India	NA	106	NA	NA	NA	NA	RHC	16.00%
Stolz et al 2008^Citation77	Switzerland	NA	123	NA	NA	Inpatients	AECOPD	TTE	22.80%
Sun et al 2019^Citation79	China	2016–2018	106	97/9	69.5±10.1	NA	Stable	TTE	22.60%
Takahashi et al 2018^Citation79	Japan	2006–2016	131	NA	NA	NA	NA	TTE	12.98%
Xiong et al 2018^Citation80	China	2015–2017	97	49/48	67.5±10.5	Lung transplants	Stable	TTE	23.71%
Xiong et al 2020^Citation81	China	NA	513	432/81	68.02	Outpatients	Stable	TTE	29.24%
Yazici et al 2019^Citation82	Turkey	2015–2018	126	119/7	66.73±9.76	Outpatients	NA	TTE	26.19%

Abbreviations: AECOPD, acute exacerbation of chronic obstructive pulmonary disease; M/F, the number of males/the number of females; NA, not available or applicable; PH, pulmonary hypertension; TTE, transthoracic echocardiography; RHC, right heart catheterization.

Figure 2 Forest plot of COPD-related PH prevalence.

Table 2 Subgroup Analyses of COPD-Related PH Prevalence

Subgroups	Number of Included Studies	COPD-Related PH
		Prevalence	Sample (n)	95% CI	I^Citation2	P value	P Within Groups
Continents
Africa	2	64.0%	372	59.4–68.3	0.0%	0.728	0.000
Asia	18	32.6%	3648	28.4–44.3	96.5%	0.000
Europe	11	30.4%	1780	23.3–37.6	91.0%	0.000
North America	7	52.6%	10 437	45.3–60.0	96.9%	0.000
Enrolment time
−2010	10	41.8%	2467	31.1–52.5	96.9%	0.000	0.992
2010–2015	4	41.2%	706	18.6–63.8	97.7%	0.000
2015-	6	42.7%	905	28.4–57.0	95.2%	0.000
Diagnostic methods for PH
TTE	23	40.7%	4165	33.3–48.2	96.4%	0.000	0.494
RHC	15	37.0%	12 180	29.0–44.9	98.3%	0.000
Mean age
>65	14	35.3%	3387	26.7–43.9	96.8%	0.000	0.082
<65	17	44.5%	12 172	38.7–50.2	96.5%	0.000
COPD classifications
I	4	24.5%	104	2.4–46.7	83.1%	0.030	0.024
II	7	34.1%	437	15.6–52.6	95.9%	0.000
III	8	38.6%	563	23.0–54.2	92.3%	0.000
IV	8	61.5%	358	46.2–76.8	90.2%	0.000
Gender
Female	14	43.5%	2110	38.0–49.1	81.5%	0.000	0.720
Male	14	42.6%	3205	33.5–51.8	95.7%	0.000
PH grades
Mild	5	30.2%	543	22.3–38.0	73.9%	0.000	0.000
Moderate	5	10.0%	543	5.7–14.3	64.3%	0.000
Severe	5	7.2%	543	1.4–13.0	90.1%	0.015
Sample source
Lung transplants	8	44.5%	10 844	37.3–51.7	97.2%	0.000	0.247
Outpatients	6	40.5%	1191	33.9–47.2	98.2%	0.000
Inpatients	7	32.3%	2130	19.4–45.2	97.8%	0.000
Sample type
Stable phase	19	38.1%	4209	30.6–45.7	96.6%	0.000	0.998
AECOPD	3	38.2%	717	30.9–45.4	98.7%	0.012

Abbreviations: AECOPD, acute exacerbation of chronic obstructive pulmonary disease; TTE, transthoracic echocardiography; PH, pulmonary hypertension; RHC, right heart catheterization.

Figure 3 Funnel plot, Egger test, and Begg test for assessing publication bias.

Figure 4 Sensitivity analysis of the COPD-related PH pooled prevalence.

Acharya V, Mugularao S, Seshadri S, Shetty RK. Assessment of diastolic dysfunction parameters and cardiac chamber size in smokers with COPD: a case control study. J Clin Diagn Res. 2018;12(1):45.

 Web of Science ®Google Scholar

Aksu F, Capan N, Aksu K, et al. C-reactive protein levels are raised in stable Chronic obstructive pulmonary disease patients independent of smoking behavior and biomass exposure. J Thorac Dis. 2013;5(4):414–421. doi:10.3978/j.issn.2072-1439.2013.06.27

 PubMed Web of Science ®Google Scholar

Alkukhun L, Baumgartner M, Budev M, Dweik RA, Tonelli AR. Electrocardiographic differences between COPD patients evaluated for lung transplantation with and without pulmonary hypertension. COPD. 2014;11(6):670–680. doi:10.3109/15412555.2014.898047

 PubMedGoogle Scholar

Andersen KH, Iversen M, Kjaergaard J, et al. Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease. J Heart Lung Transplant. 2012;31(4):373–380. doi:10.1016/j.healun.2011.11.020

 PubMed Web of Science ®Google Scholar

Blanco I, Valeiro B, Torres-Castro R, et al. Effects of pulmonary hypertension on exercise capacity in patients with chronic obstructive pulmonary disease. Arch Bronconeumol. 2020;56(8):499–505. doi:10.1016/j.arbr.2019.10.018

 PubMed Web of Science ®Google Scholar

Buklioska-Ilievska D, Minov J, Kochovska-Kamchevska N, et al. Cardiovascular comorbidity in patients with chronic obstructive pulmonary disease: echocardiography changes and their relation to the level of airflow limitation. Open Access Maced J Med Sci. 2019;7(21):3568–3573. doi:10.3889/oamjms.2019.848

 PubMedGoogle Scholar

Chaouat A, Savale L, Chouaid C, et al. Role for interleukin-6 in COPD-related pulmonary hypertension. Chest. 2009;136(3):678–687. doi:10.1378/chest.08-2420

 PubMed Web of Science ®Google Scholar

Chen X, Liu K, Wang Z, et al. Computed tomography measurement of pulmonary artery for diagnosis of COPD and its comorbidity pulmonary hypertension. Int J Chron Obstruct Pulmon Dis. 2015;10:2525–2533. doi:10.2147/COPD.S94211

 PubMed Web of Science ®Google Scholar

Fayngersh V, Drakopanagiotakis F, Dennis McCool F, Klinger JR. Pulmonary hypertension in a stable community-based COPD population. Lung. 2011;189(5):377–382. doi:10.1007/s00408-011-9315-2

 PubMed Web of Science ®Google Scholar

Freixa X, Portillo K, Paré C, et al. Echocardiographic abnormalities in patients with COPD at their first hospital admission. Eur Respir J. 2013;41(4):784–791. doi:10.1183/09031936.00222511

 PubMed Web of Science ®Google Scholar

Gartman EJ, Blundin M, Klinger JR, Yammine J, Roberts MB, Dennis McCool F. Initial risk assessment for pulmonary hypertension in patients with COPD. Lung. 2012;190(1):83–89. doi:10.1007/s00408-011-9346-8

 PubMed Web of Science ®Google Scholar

Gupta KK, Roy B, Chaudhary SC, et al. Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease and its correlation with stages of chronic obstructive pulmonary disease, exercising capacity, and quality of life. J Family Med Prim Care. 2018;7(1):53–57. doi:10.4103/jfmpc.jfmpc_18_17

 PubMedGoogle Scholar

Halvani A, Haddad H. Comparison of the factors influencing pulmonary arterial pressure in smoker and non-smoker COPD patients with pulmonary hypertension. Tanaffos. 2019;18(1):41–46.

 PubMedGoogle Scholar

Hayes D Jr, Tumin D, Budev MM, et al. Adverse outcomes associated with pulmonary hypertension in chronic obstructive pulmonary disease after bilateral lung transplantation. Respir Med. 2017;128:102–108. doi:10.1016/j.rmed.2017.04.010

 PubMed Web of Science ®Google Scholar

Hilde JM, Skjørten I, Hansteen V, et al. Assessment of right ventricular afterload in COPD. COPD. 2016;13(2):176–185. doi:10.3109/15412555.2015.1057275

 PubMedGoogle Scholar

Jethani V, Sindhwani G. Chronic obstructive pulmonary disease and cardiac comorbidities: a cross-sectional study. Lung India. 2016;33(6):697. doi:10.4103/0970-2113.192866

 PubMedGoogle Scholar

Kwon YS, Chi SY, Shin HJ, et al. Plasma C-reactive protein and endothelin-1 level in patients with chronic obstructive pulmonary disease and pulmonary hypertension. J Korean Med Sci. 2010;25(10):1487–1491. doi:10.3346/jkms.2010.25.10.1487

 PubMed Web of Science ®Google Scholar

Malinovschi A, Masoero M, Bellocchia M, et al. Severe vitamin D deficiency is associated with frequent exacerbations and hospitalization in COPD patients. Respir Res. 2014;15(1):131.

 PubMed Web of Science ®Google Scholar

Matsuyama W, Ohkubo R, Michizono K, et al. Usefulness of transcutaneous Doppler jugular venous echo to predict pulmonary hypertension in COPD patients. Eur Respir J. 2001;17(6):1128–1131. doi:10.1183/09031936.01.00088401

 PubMed Web of Science ®Google Scholar

Mohamed Hoesein FA, Besselink T, Pompe E, et al. Accuracy of CT pulmonary artery diameter for pulmonary hypertension in end-stage COPD. Lung. 2016;194(5):813–819. doi:10.1007/s00408-016-9926-8

 PubMed Web of Science ®Google Scholar

Mohamed MF, Ali A, Abbas A, Awad MS, Gouda M, Sediq AM. Mean platelet volume as a predictor of pulmonary hypertension in patients with stable COPD. Int J Chron Obstruct Pulmon Dis. 2019;14:1099–1108. doi:10.2147/COPD.S176413

 PubMed Web of Science ®Google Scholar

Nakahara Y, Taniguchi H, Kimura T, et al. Exercise hypoxaemia as a predictor of pulmonary hypertension in COPD patients without severe resting hypoxaemia. Respirology. 2017;22(1):120–125. doi:10.1111/resp.12863

 PubMed Web of Science ®Google Scholar

Nakayama S, Chubachi S, Sakurai K, et al. Characteristics of chronic obstructive pulmonary disease patients with pulmonary hypertension assessed by echocardiography in a three-year observational cohort study. Int J Chron Obstruct Pulmon Dis. 2020;15:487–499. doi:10.2147/COPD.S230952

 PubMed Web of Science ®Google Scholar

Nathan SD, Barnett SD, King CS, et al. Impact of the new definition for pulmonary hypertension in patients with lung disease: an analysis of the United Network for organ sharing database. Pulm Circ. 2021;11(2):2045894021999960. doi:10.1177/2045894021999960

 Web of Science ®Google Scholar

Portillo K, Torralba Y, Blanco I, et al. Pulmonary hemodynamic profile in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2015;10:1313–1320. doi:10.2147/COPD.S78180

 PubMed Web of Science ®Google Scholar

Sertogullarindan B, Gumrukcuoglu HA, Sezgi C, Akil MA. Frequency of pulmonary hypertension in patients with COPD due to biomass smoke and tobacco smoke. Int J Med Sci. 2012;9(6):406–412. doi:10.7150/ijms.4715

 PubMed Web of Science ®Google Scholar

Seyhan EC, Özgül MA, Tutar N, Ömür I, Uysal A, Altin S. Red blood cell distribution and survival in patients with chronic obstructive pulmonary disease. COPD. 2013;10(4):416–424. doi:10.3109/15412555.2012.758697

 PubMedGoogle Scholar

El-Shabrawy M, Eldamanhory AS. Study of cardiovascular diseases in hospitalized AECOPD patients. Egypt J Chest Dis Tuberc. 2017;66(1):17–25. doi:10.1016/j.ejcdt.2016.08.008

 Web of Science ®Google Scholar

Shin S, King CS, Brown AW, et al. Pulmonary artery size as a predictor of pulmonary hypertension and outcomes in patients with chronic obstructive pulmonary disease. Respir Med. 2014;108(11):1626–1632. doi:10.1016/j.rmed.2014.08.009

 PubMed Web of Science ®Google Scholar

Sims MW, Margolis DJ, Localio AR, Panettieri RA, Kawut SM, Christie JD. Impact of pulmonary artery pressure on exercise function in severe COPD. Chest. 2009;136(2):412–419. doi:10.1378/chest.08-2739

 PubMed Web of Science ®Google Scholar

Skjørten I, Hilde JM, Melsom MN, Hansteen V, Steine K, Humerfelt S. Pulmonary artery pressure and PaO2 in chronic obstructive pulmonary disease. Respir Med. 2013;107(8):1271–1279. doi:10.1016/j.rmed.2013.03.021

 PubMed Web of Science ®Google Scholar

Sridhara VSHK, Acharya V. Comorbidities of chronic obstructive pulmonary disease and their affect on hospitalization of patients in a tertiary care hospital. J Community Hosp Intern Med Perspect. 2021;11(1):120–123. doi:10.1080/20009666.2020.1843823

 PubMed Web of Science ®Google Scholar

Stolz D, Christ-Crain M, Morgenthaler NG, et al. Plasma pro-adrenomedullin but not plasma pro-endothelin predicts survival in exacerbations of COPD. Chest. 2008;134(2):263–272.

 PubMed Web of Science ®Google Scholar

Takahashi T, Yoshihisa A, Sugimoto K, et al. Associations between diabetes mellitus and pulmonary hypertension in chronic respiratory disease patients. PLoS One. 2018;13(10):e0205008. doi:10.1371/journal.pone.0205008

 PubMed Web of Science ®Google Scholar

Xiong W, Zhao Y, Gong S, Zhao Q, Liu J. Prophylactic function of excellent compliance with LTOT in the development of pulmonary hypertension due to COPD with hypoxemia. Pulm Circ. 2018;8(2):2045894018765835. doi:10.1177/2045894018765835

 Web of Science ®Google Scholar

Xiong M, Guo M, Huang D, Li J, Zhou Y. TRPV1 genetic polymorphisms and risk of COPD or COPD combined with PH in the Han Chinese population. Cell Cycle. 2020;19(22):3066–3073. doi:10.1080/15384101.2020.1831246

 PubMed Web of Science ®Google Scholar

Yazici O, Tas Gulen S, Eryilmaz U, Omurlu IK. The evaluation of cardiac functions according to chronic obstructive pulmonary disease groups. Aging Male. 2020;23(2):106–111. doi:10.1080/13685538.2019.1606191

 PubMed Web of Science ®Google Scholar

Nici L, Mammen MJ, Charbek E, et al. Pharmacologic management of chronic obstructive pulmonary disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020;201(9):e56–e69. doi:10.1164/rccm.202003-0625ST

 PubMed Web of Science ®Google Scholar