The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.
Research Article| Volume 42, ISSUE 3, P377-389, March 2023

Download started.


Smoking history and pulmonary arterial hypertension: Demographics, onset, and outcomes

Published:October 17, 2022DOI:


      Smoking prevalence and its association with pulmonary arterial hypertension (PAH) outcomes have not been described in patients in the United States.


      Using the US-based Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), the prevalence, demographics, and outcomes in ever- versus never-smokers with PAH were determined.


      Ever-smoking status was more prevalent in males (61.7%) than in females (42.9%) enrolled in REVEAL. Ever-smokers were older than never-smokers at the time of PAH diagnosis and REVEAL enrollment. The time to first hospitalization, transplant-free survival, and survival did not differ between ever- and never-smokers overall; however, in newly diagnosed males, ever-smoking was associated with earlier death (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.1–3.0; p = 0.0199), the composite of transplant or death (HR 2.2, 95% CI 1.4–3.6; p = 0.0008), and first hospitalization (HR 1.8, 95% CI 1.2–2.7; p = 0.0063), though smoking exposure (pack-years) did not differ between newly and previously diagnosed males.


      REVEAL PAH data demonstrate that smoking prevalence in male PAH patients is disproportionate. The prevalence of cigarette smoking was significantly higher in males than females enrolled in REVEAL. Ever-smoking status was associated with increased age at PAH diagnosis and, in newly diagnosed male PAH patients, earlier time to hospitalization and shorter survival after PAH diagnosis.



      6MWD (6-minute walk distance), APAH (associated pulmonary arterial hypertension), BNP (brain natriuretic peptide), CI (confidence interval), COPD (chronic obstructive pulmonary disease), COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension), DLCO (diffusion capacity for carbon monoxide), eGFR (estimated glomerular filtration rate), ERA (endothelin receptor antagonist), FEV1 (forced expiratory volume in 1 second), FPAH (familial pulmonary arterial hypertension), FVC (forced vital capacity), HIV (human immunodeficiency virus), HR (hazard ratio), IPAH (idiopathic pulmonary arterial hypertension), IQR (interquartile range), mPAP (mean pulmonary arterial pressure), n/a (not applicable), NC (not calculated), OSA (obstructive sleep apnea), PAH (pulmonary arterial hypertension), PCWP (pulmonary capillary wedge pressure), PDE5i (phosphodiesterase 5 inhibitor), PH (pulmonary hypertension), PoPH (portopulmonary hypertension), PPH (primary pulmonary hypertension), PVOD (pulmonary veno-occlusive disease), PVR (pulmonary vascular resistance), RAP (right atrial pressure), REVEAL (Registry to Evaluate Early and Long-term PAH Disease Management), RHC (right heart catheterization), SD (standard deviation), WHO (World Health Organization)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The Journal of Heart and Lung Transplantation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Liebow AA
        Pulmonary emphysema with special reference to vascular changes.
        Am Rev Respir Dis. 1959; 80: 67-93
        • Peinado VI
        • Barbera JA
        • Ramirez J
        • et al.
        Endothelial dysfunction in pulmonary arteries of patients with mild COPD.
        Am J Physiol. 1998; 274: L908-L913
        • Sekhon HS
        • Wright JL
        • Churg A
        Cigarette smoke causes rapid cell proliferation in small airways and associated pulmonary arteries.
        Am J Physiol. 1994; 267: L557-L563
        • Wu J
        • Huang Q
        • Li Q
        • et al.
        Increased methyl-CpG-binding domain protein 2 promotes cigarette smoke-induced pulmonary hypertension.
        Front Oncol. 2022; 12 (Jun 16)879793
        • Abenhaim L
        • Moride Y
        • Brenot F
        • et al.
        Appetite suppressant drugs and the risk of primary pulmonary hypertension International Primary Pulmonary Hypertension Study Group.
        N Engl J Med. 1996; 335: 609-616
        • Keusch S
        • Hildenbrand FF
        • Bollmann T
        • et al.
        Tobacco smoke exposure in pulmonary arterial and thromboembolic pulmonary hypertension.
        Respiration. 2014; 88: 38-45
        • Hoeper MM
        • Pausch C
        • Grunig E
        • et al.
        Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry.
        J Heart Lung Transplant. 2020; 39: 1435-1444
        • Wong HT
        • Chee KH
        • Chong AW
        Pulmonary hypertension and echocardiogram parameters in obstructive sleep apnea.
        Eur Arch Otorhinolaryngol. 2017; 274: 2601-2606
        • Jo HH
        • Park MJ
        • Shin HS
        • et al.
        Adverse effect of smoking on cross-sectional area of small pulmonary vessel and arterial stiffness in healthy smokers without COPD.
        Clin Respir J. 2019; 13: 368-375
        • Zhou S
        • Li M
        • Zeng D
        • Sun G
        • Zhou J
        • Wang R
        Effects of basic fibroblast growth factor and cyclin D1 on cigarette smoke-induced pulmonary vascular remodeling in rats.
        Exp Ther Med. 2015; 9: 33-38
        • Li Q
        • Wu J
        • Xu Y
        • Liu L
        • Xie J
        Role of RASEF hypermethylation in cigarette smoke-induced pulmonary arterial smooth muscle remodeling.
        Respir Res. 2019; 20: 52-66
        • Schiess R
        • Senn O
        • Fischler M
        • et al.
        Tobacco smoke: a risk factor for pulmonary arterial hypertension.
        Chest. 2010; 138: 1086-1092
        • Hoeper M
        • Dwivedi K
        • Pousch C
        • et al.
        Phenotyping of idiopathic pulmonary arterial hypertension: a registry analysis.
        Lancet Respir Med. 2022; 10: 937-948
        • Badesch DB
        • Raskob GE
        • Elliott CG
        • et al.
        Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry.
        Chest. 2010; 137: 376-387
        • Poms A
        • Turner M
        • Farber HW
        • Meltzer LA
        • McGoon MD
        Comorbid conditions and outcomes in patients with pulmonary arterial hypertension: a REVEAL registry analysis.
        Chest. 2013; 144: 169-176
        • Benza RL
        • Miller DP
        • Gomberg-Maitland M
        • et al.
        Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL).
        Circulation. 2010; 122: 164-172
        • Benza RL
        • Miller DP
        • Barst RJ
        • Badesch DB
        • Frost AE
        • McGoon MD
        An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL registry.
        Chest. 2012; 142: 448-456
        • Tsai W
        • Jewell N
        • Want M
        A note on the product-limit estimator under right censoring and left truncation.
        Biometrika. 1987; 74: 883-886
        • Keidin N
        Independent delayed entry.
        (editors)in: Klein JP Goel PK Survival Analysis: State of the Art. Kluwer Academic Publishing, Dordrecht, the Netherlands1992: 309-326
        • Levey AS
        • Stevens LA
        • Schmid CH
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Hoeper MM
        • Vonk-Noordegraaf A
        Is there a vanishing pulmonary capillary syndrome?.
        Lancet Respir Med. 2017; 5: 676-678
        • Becklake MR
        • Lalloo U
        The ‘healthy smoker’: a phenomenon of health selection?.
        Respiration. 1990; 57: 137-144
        • Radon K
        • Goldberg M
        • Becklake M
        Healthy worker effect in cohort studies on chronic bronchitis.
        Scan J Work Environ Health. 2002; 28: 328-332
        • Troosters T
        • Gosselink R
        • Decramer M
        Six minute walking distance in healthy elderly subjects.
        Eur Respir J. 1999; 14: 270-274
        • Filion KB
        • Steffen LM
        • Duval S
        • Jacobs Jr., DR
        • Blackburn H
        • Luepker RV
        Trends in smoking among adults from 1980 to 2009: the Minnesota heart survey.
        Am J Public Health. 2012; 102: 705-713
        • Botros L
        • Vonk Noordegraaf A
        • Aman J
        Vanishing vessels aboding pulmonary disease: a role for VEGFR2.
        Eur Respir J. 2020; 552000326
        • Washko GR
        • Nardelli P
        • Ash SY
        • et al.
        Arterial vascular pruning, right ventricular size, and clinical outcomes in chronic obstructive pulmonary disease.
        Am Respir Crit Care Med. 2019; 200: 454-461
        • Eyries M
        • Montani D
        • Girerd B
        • et al.
        Familial pulmonary arterial hypertension by KDR heterozygous loss of function.
        Eur Respir J. 2020; 551902165
        • Montani D
        • Lau EM
        • Descatha A
        • et al.
        Occupational exposure to organic solvents: a risk factor for pulmonary veno-occlusive disease.
        Eur Respir J. 2015; 46: 1721-1731
        • Montani D
        • Achouh L
        • Dorfmuller P
        • et al.
        Pulmonary veno-occlusive disease: characteristics and outcome of 24 cases confirmed by histology.
        Medicine (Baltimore). 2008; 87: 220-233
        • Rich S
        • Dantzker DR
        • Ayres SM
        • et al.
        Primary pulmonary hypertension: a national prospective study.
        Ann Intern Med. 1987; 107: 216-223
        • D'Alonzo GE
        • Barst RJ
        • Ayres SM
        • et al.
        Survival in patients with primary pulmonary hypertension: results from a national prospective registry.
        Ann Intern Med. 1991; 115: 343-349
        • Hemnes AR
        • Beck GJ
        • Newman JH
        • et al.
        PVDOMICS: a multi-center study to improve understanding of pulmonary vascular disease through phenomics.
        Circ Res. 2017; 121: 1136-1139