, Volume 196, Issue 3, pp 315–319 | Cite as

Effect of 6-min Walk Test on pro-BNP Levels in Patients with Pulmonary Arterial Hypertension

  • Vikas Pathak
  • Robert Aris
  • Brian C. Jensen
  • Wei Huang
  • Hubert James Ford



Plasma pro-BNP (brain natriuretic peptide) levels are often elevated in response to right ventricular (RV) volume and pressure overload, parameters potentially affected by exercise. Plasma pro-BNP levels change in association with long-term changes in pulmonary hemodynamics, thereby serving as a potential biomarker in pulmonary arterial hypertension (PAH). The 6-min Walk Test (6MWT) and pro-BNP level are often checked in a single office visit. There is no universal standard for measuring Pro-BNP levels relative to the timing of the 6MWT. Based on the studies in normal subjects indicating that pro-BNP levels changes after exercise, we hypothesized that the pro-BNP might rise after the 6MWT in PAH patients, potentially impacting clinical decisions.


Patients at our center with WHO Group 1 PAH on active therapy at a stable dose for 30 days or more were enrolled. After resting the patient for 30 min, blood was drawn for baseline pro-BNP and a 6MWT was performed. Pro-BNP levels were drawn immediately after the 6MWT and 1 and 2 h later. Pro-BNP was measured using a commercially available ELISA kit. The levels before exercise and after exercise were compared using student’s paired t tests.


There were 17 females and 3 male subjects. The mean age was 53 ± 11 years. Seven patients had systemic lupus erythematosus-related PAH, six had idiopathic PAH, three had scleroderma, three had portopulmonary hypertension, and one had HIV-related PAH. The mean PA pressure was 50 ± 15 mmHg with a mean pulmonary vascular resistance of 10 ± 4 Wood units. The majority of the patients were on multimodality PAH therapy, including parenteral prostacyclins. Mean 6MWT distance was 377 ± 140 m. In 14/20 patients, the pro-BNP level increased immediately after the 6MWT; in 12/20 patients, the pro-BNP level was elevated at 1 h post exercise. In the majority of the patients, the pro-BNP fell to baseline 2 h post 6MWT.


There appears to be a trend of pro-BNP level increasing immediately after exercise and continuing to be elevated at 1 h. Pro-BNP levels then return to baseline at 2 h post 6MWT.


Pulmonary hypertension Pro-BNP Six-min walk test 


Author Contributions

VP: Study design, conducted the study, data collection, manuscript preparation. RA: Study design, manuscript preparation. BJ: Running the samples, manuscript preparation. WH: Running the samples, manuscript preparation. HJF: Study design, patient identification, manuscript preparation.


This study was funded by Division of pulmonary and critical care medicine, University of North Carolina at Chapel Hill.

Compliance with Ethical Standards

Conflict of interest

The authors report no real or potential conflict of interest.


  1. 1.
    D’Alonzo GE, Barst RJ, Ayres SM et al (1991) Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 115(5):343–349CrossRefPubMedGoogle Scholar
  2. 2.
    Rubin LJ (1997) Primary pulmonary hypertension. N Engl J Med 336(2):111–117CrossRefPubMedGoogle Scholar
  3. 3.
    Rich S, Dantzker DR, Ayres SM et al (1987) Primary pulmonary hypertension. A national prospective study. Ann Intern Med 107(2):216–223CrossRefPubMedGoogle Scholar
  4. 4.
    Miyamoto S, Nagaya N, Satoh T et al (2000) Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med 161(2 Pt 1):487–492CrossRefPubMedGoogle Scholar
  5. 5.
    Sun XG, Hansen JE, Oudiz RJ et al (2001) Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation 104(4):429–435CrossRefPubMedGoogle Scholar
  6. 6.
    Wensel R, Opitz CF, Ewert R et al (2000) Effects of iloprost inhalation on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension. Circulation 101(20):2388–2392CrossRefPubMedGoogle Scholar
  7. 7.
    Higenbottam TW, Butt AY, Dinh-Xaun AT et al (1998) Treatment of pulmonary hypertension with the continuous infusion of a prostacyclin analogue, iloprost. Heart 79(2):175–179CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Channick RN, Simonneau G, Sitbon O et al (2001) Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 358(9288):1119–1123CrossRefPubMedGoogle Scholar
  9. 9.
    Galie N, Humbert M, Vachiery JL et al (2002) Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 39(9):1496–1502CrossRefPubMedGoogle Scholar
  10. 10.
    Olschewski H, Simonneau G, Galie N et al (2002) Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 347(5):322–329CrossRefPubMedGoogle Scholar
  11. 11.
    Kruger S, Graf J, Kunz D et al (2002) Brain natriuretic peptide levels predict functional capacity in patients with chronic heart failure. J Am Coll Cardiol 40(4):718–722CrossRefPubMedGoogle Scholar
  12. 12.
    Tsutamoto T, Wada A, Maeda K et al (1997) Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction. Circulation 96(2):509–516CrossRefPubMedGoogle Scholar
  13. 13.
    Omland T, Aakvaag A, Bonarjee VV et al (1996) Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide. Circulation 93(11):1963–1969CrossRefPubMedGoogle Scholar
  14. 14.
    Koglin J, Pehlivanli S, Schwaiblmair M et al (2001) Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure. J Am Coll Cardiol 38(7):1934–1941CrossRefPubMedGoogle Scholar
  15. 15.
    Burger MR, Burger AJ (2001) BNP in decompensated heart failure: diagnostic, prognostic and therapeutic potential. Curr Opin Investig Drugs 2(7):929–935PubMedGoogle Scholar
  16. 16.
    Bolger AP, Sharma R, Li W et al (2002) Neurohormonal activation and the chronic heart failure syndrome in adults with congenital heart disease. Circulation 106(1):92–99CrossRefPubMedGoogle Scholar
  17. 17.
    Krupicka J, Janota T, Kasalova Z et al (2010) Effect of short-term maximal exercise on BNP plasma levels in healthy individuals. Physiol Res 59(4):625–628PubMedGoogle Scholar
  18. 18.
    Park MH, Scott RL, Uber PA et al (2004) Usefulness of B-type natriuretic peptide as a predictor of treatment outcome in pulmonary arterial hypertension. Congest Heart Fail 10(5):221–225CrossRefPubMedGoogle Scholar
  19. 19.
    Leuchte HH, Holzapfel M, Baumgartner RA et al (2005) Characterization of brain natriuretic peptide in long-term follow-up of pulmonary arterial hypertension. Chest 128(4):2368–2374CrossRefPubMedGoogle Scholar
  20. 20.
    McLaughlin VV, Archer SL, Badesch DB et al (2009) ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol 53(17):1573–1619CrossRefPubMedGoogle Scholar
  21. 21.
    Nagaya N, Nishikimi T, Uematsu M et al (2000) Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation 102(8):865–870CrossRefPubMedGoogle Scholar
  22. 22.
    Fijalkowska A, Kurzyna M, Torbicki A et al (2006) Serum N-terminal brain natriuretic peptide as a prognostic parameter in patients with pulmonary hypertension. Chest 129(5):1313–1321CrossRefPubMedGoogle Scholar
  23. 23.
    McGoon M, Gutterman D, Steen V et al (2004) Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 126(1 Suppl):14S-34SPubMedGoogle Scholar
  24. 24.
    Galie N, Torbicki A, Barst R et al (2004) Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 25(24):2243–2278CrossRefPubMedGoogle Scholar
  25. 25.
    Barst RJ, McGoon M, Torbicki A et al (2004) Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 43(12 Suppl S):40S-47SPubMedGoogle Scholar
  26. 26.
    Humbert M, Sitbon O, Simonneau G (2004) Treatment of pulmonary arterial hypertension. N Engl J Med 351(14):1425–1436CrossRefPubMedGoogle Scholar
  27. 27.
    ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories (2002) ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 166(1):111–117CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Pulmonary and Critical Care Medicine, Department of MedicineWakeMed Health and HospitalsRaleighUSA
  2. 2.Division of Pulmonary and Critical Care Medicine, Department of MedicineUniversity of North CarolinaChapel HillUSA
  3. 3.Division of Cardiology and UNC McAllister Heart InstituteUniversity of North CarolinaChapel HillUSA

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