Robert P Frantz1, Harrison W Farber2, David B Badesch3, C Greg Elliott4, Adaani E Frost5, Michael D McGoon6, Carol Zhao7, David R Mink8, Mona Selej7, Raymond L Benza9. 1. Mayo Clinic, Rochester, MN. Electronic address: frantz.robert@mayo.edu. 2. Pulmonary Center, Boston University School of Medicine, Boston, MA. 3. University of Colorado, Denver, CO. 4. Intermountain Medical Center and the University of Utah School of Medicine, Salt Lake City, UT. 5. Houston Methodist Lung Center, Weill Cornell Medical College, Houston, TX. 6. Mayo Clinic, Rochester, MN. 7. Actelion Pharmaceuticals US, Inc, South San Francisco, CA. 8. ICON Clinical Research, San Francisco, CA. 9. Allegheny General Hospital, Pittsburgh, PA.
Abstract
BACKGROUND: Plasma brain natriuretic peptide (BNP) level is a prognostic biomarker in pulmonary arterial hypertension (PAH). Its impact on long-term overall survival (OS) was investigated in the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL), a 5-year observational, multicenter, US registry of patients with PAH. METHODS: Patients were ≥ 18 years of age, met right heart catheterization criteria at rest, had World Health Organization group I PAH, and had BNP measurement at enrollment. Optimal BNP threshold was obtained via receiver operating characteristic curve analysis. OS was compared in patients with low (≤ 340 pg/mL) vs high (> 340 pg/mL) BNP at baseline; changes between baseline and last assessment were also examined. Patients were categorized based on baseline (low or high) and follow-up (low or high) BNP values; hazard ratios (HRs) for OS were estimated and compared using Cox regression. RESULTS: Overall, 1,426 patients were analyzed. Mortality risk was significantly higher in patients with baseline high vs low BNP (HR, 3.6; 95% CI, 3.0-4.2). BNP change analysis at ≤ 1 year postenrollment demonstrated that the low-low group had the lowest and the high-high group had the highest 5-year mortality risk (HR, 0.23; 95% CI, 0.19-0.27). Changes in BNP score also correlated with change of risk of death. CONCLUSIONS: Baseline BNP threshold of 340 pg/mL strongly predicted survival up to 5 years in patients with PAH. A BNP reduction at 1 year since enrollment was associated with decreased mortality risk, whereas an increase in BNP at 1 year was associated with an increased mortality risk, supporting BNP as a surrogate marker of PAH survival.
BACKGROUND: Plasma brain natriuretic peptide (BNP) level is a prognostic biomarker in pulmonary arterial hypertension (PAH). Its impact on long-term overall survival (OS) was investigated in the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL), a 5-year observational, multicenter, US registry of patients with PAH. METHODS:Patients were ≥ 18 years of age, met right heart catheterization criteria at rest, had World Health Organization group I PAH, and had BNP measurement at enrollment. Optimal BNP threshold was obtained via receiver operating characteristic curve analysis. OS was compared in patients with low (≤ 340 pg/mL) vs high (> 340 pg/mL) BNP at baseline; changes between baseline and last assessment were also examined. Patients were categorized based on baseline (low or high) and follow-up (low or high) BNP values; hazard ratios (HRs) for OS were estimated and compared using Cox regression. RESULTS: Overall, 1,426 patients were analyzed. Mortality risk was significantly higher in patients with baseline high vs low BNP (HR, 3.6; 95% CI, 3.0-4.2). BNP change analysis at ≤ 1 year postenrollment demonstrated that the low-low group had the lowest and the high-high group had the highest 5-year mortality risk (HR, 0.23; 95% CI, 0.19-0.27). Changes in BNP score also correlated with change of risk of death. CONCLUSIONS: Baseline BNP threshold of 340 pg/mL strongly predicted survival up to 5 years in patients with PAH. A BNP reduction at 1 year since enrollment was associated with decreased mortality risk, whereas an increase in BNP at 1 year was associated with an increased mortality risk, supporting BNP as a surrogate marker of PAH survival.
Authors: Raymond L Benza; Dave P Miller; Robyn J Barst; David B Badesch; Adaani E Frost; Michael D McGoon Journal: Chest Date: 2012-08 Impact factor: 9.410
Authors: Mark H Williams; Clive E Handler; Raza Akram; Colette J Smith; Clare Das; Joanna Smee; Devaki Nair; Christopher P Denton; Carol M Black; John G Coghlan Journal: Eur Heart J Date: 2006-04-27 Impact factor: 29.983
Authors: Michael D McGoon; Raymond L Benza; Pilar Escribano-Subias; Xin Jiang; Dave P Miller; Andrew J Peacock; Joanna Pepke-Zaba; Tomas Pulido; Stuart Rich; Stephan Rosenkranz; Samy Suissa; Marc Humbert Journal: J Am Coll Cardiol Date: 2013-12-24 Impact factor: 24.094
Authors: Gerald Simonneau; Michael A Gatzoulis; Ian Adatia; David Celermajer; Chris Denton; Ardeschir Ghofrani; Miguel Angel Gomez Sanchez; R Krishna Kumar; Michael Landzberg; Roberto F Machado; Horst Olschewski; Ivan M Robbins; Rogiero Souza Journal: J Am Coll Cardiol Date: 2013-12-24 Impact factor: 24.094
Authors: Raymond L Benza; Dave P Miller; Mardi Gomberg-Maitland; Robert P Frantz; Aimee J Foreman; Christopher S Coffey; Adaani Frost; Robyn J Barst; David B Badesch; C Gregory Elliott; Theodore G Liou; Michael D McGoon Journal: Circulation Date: 2010-06-28 Impact factor: 29.690
Authors: N Nagaya; T Nishikimi; Y Okano; M Uematsu; T Satoh; S Kyotani; S Kuribayashi; S Hamada; M Kakishita; N Nakanishi; M Takamiya; T Kunieda; H Matsuo; K Kangawa Journal: J Am Coll Cardiol Date: 1998-01 Impact factor: 24.094
Authors: Margaret M Redfield; Richard J Rodeheffer; Steven J Jacobsen; Douglas W Mahoney; Kent R Bailey; John C Burnett Journal: J Am Coll Cardiol Date: 2002-09-04 Impact factor: 24.094
Authors: Nadine Al-Naamani; Harold I Palevsky; David J Lederer; Evelyn M Horn; Stephen C Mathai; Kari E Roberts; Russell P Tracy; Paul M Hassoun; Reda E Girgis; Daichi Shimbo; Wendy S Post; Steven M Kawut Journal: Ann Am Thorac Soc Date: 2016-01
Authors: Jenny Y Chen; Megan Griffiths; Jun Yang; Melanie K Nies; Rachel L Damico; Catherine E Simpson; R Dhananjay Vaidya; Stephanie Brandal; D Dunbar Ivy; Eric D Austin; William C Nichols; Michael W Pauciulo; Katie Lutz; Erika B Rosenzweig; Russel Hirsch; Delphine Yung; Allen D Everett Journal: J Pediatr Date: 2020-08 Impact factor: 4.406
Authors: Catherine E Simpson; Rachel L Damico; Paul M Hassoun; Lisa J Martin; Jun Yang; Melanie K Nies; R Dhananjay Vaidya; Stephanie Brandal; Michael W Pauciulo; Eric D Austin; D Dunbar Ivy; William C Nichols; Allen D Everett Journal: Chest Date: 2020-01-25 Impact factor: 9.410
Authors: Sean Agbor-Enoh; Michael A Solomon; Samuel B Brusca; Jason M Elinoff; Yvette Zou; Moon Kyoo Jang; Hyesik Kong; Cumhur Y Demirkale; Junfeng Sun; Fayaz Seifuddin; Mehdi Pirooznia; Hannah A Valantine; Carl Tanba; Abhishek Chaturvedi; Grace M Graninger; Bonnie Harper; Li-Yuan Chen; Justine Cole; Manreet Kanwar; Raymond L Benza; Ioana R Preston Journal: Circulation Date: 2022-08-25 Impact factor: 39.918
Authors: Raymond L Benza; Mark Doyle; David Lasorda; Kishan S Parikh; Priscilla Correa-Jaque; Nima Badie; Greg Ginn; Sophia Airhart; Veronica Franco; Manreet K Kanwar; Srinivas Murali; Amresh Raina; Rahul Agarwal; Sudarshan Rajagopal; Jason White; Robert Biederman Journal: Chest Date: 2019-06-29 Impact factor: 9.410
Authors: Catherine E Simpson; Jenny Y Chen; Rachel L Damico; Paul M Hassoun; Lisa J Martin; Jun Yang; Melanie Nies; Megan Griffiths; R Dhananjay Vaidya; Stephanie Brandal; Michael W Pauciulo; Katie A Lutz; Anna W Coleman; Eric D Austin; Dunbar D Ivy; William C Nichols; Allen D Everett Journal: Eur Respir J Date: 2020-04-16 Impact factor: 16.671
Authors: Nazzareno Galiè; Richard N Channick; Robert P Frantz; Ekkehard Grünig; Zhi Cheng Jing; Olga Moiseeva; Ioana R Preston; Tomas Pulido; Zeenat Safdar; Yuichi Tamura; Vallerie V McLaughlin Journal: Eur Respir J Date: 2019-01-24 Impact factor: 16.671
Authors: Samantha L Wronski; Margaret Mordin; Kim Kelley; Rebekah H Anguiano; Peter Classi; Eric Shen; Scott Manaker Journal: Lung Date: 2019-11-13 Impact factor: 2.584