title: Effect of Age on Phenotype and Outcomes in Pulmonary Arterial Hypertension Trials.
abstract: In recent years, the population of patients with pulmonary arterial hypertension (PAH) has changed dramatically, including more advanced age at diagnosis. We hypothesized that older patients have a distinct clinical profile with different disease characteristics and response to intervention.
  
  
  
  All previously published treatment studies for PAH conducted by United Therapeutics including seven randomized, placebo-controlled trials and one extension study were included and analyzed to assess the association of age with various demographic, functional, hemodynamic, and outcome variables.
  
  
  
  A total of 2,627 patients across three age groups were included: ≤ 50 (n = 1,438, 54.7%), 51 to 64 (n = 780, 29.7%), and ≥ 65 years (n = 409, 15.6%). In comparison with the youngest group, the oldest age group had higher proportions of connective tissue disease-associated etiology (range across the studies, 27%-49% vs 13%-21%), higher proportions of New York Heart Association Functional classes III and IV (74%-91% vs 57%-84%), shorter baseline 6-min walk distance (6MWD) (261-316 vs 335-371 m), better hemodynamic measurements including lower baseline mean pulmonary artery pressure (48-51 vs 58-63 mmHg), and smaller changes in 6MWD from baseline to endpoint (-5.6 to 24 vs 14-43 m). Age remained associated with change in 6MWD when adjusting for covariates in multivariate analyses.
  
  
  
  For the first time, using data from large randomized controlled trials, this study characterizes the different phenotype and outcomes of older patients with PAH, which includes different disease etiology, diminished functional status, and decreased response to intervention. This may have significant implications for the management of this patient population and design of future therapy trials.
authors.affiliation: Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Rose
authors.affiliation: Department of Biostatistics, United Therapeutics Corporation, Research Triangle Park, NC.
authors.forename: Jody M
authors.initials: JM
authors.lastname: Cleveland
authors.affiliation: Department of Biostatistics, United Therapeutics Corporation, Research Triangle Park, NC.
authors.forename: Youlan
authors.initials: Y
authors.lastname: Rao
authors.affiliation: Department of Pulmonary and Critical Care, Southside Regional Medical Center, Petersburg, VA.
authors.forename: Omar A
authors.initials: OA
authors.lastname: Minai
authors.affiliation: Department of Pulmonary, Allergy, and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH. Electronic address: tonella@ccf.org.
authors.forename: Adriano R
authors.initials: AR
authors.lastname: Tonelli
mesh_terms: D000367:Age Factors; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003240:Connective Tissue Diseases / Q000150:complications; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011669:Pulmonary Wedge Pressure; D016032:Randomized Controlled Trials as Topic; D000068581:Tadalafil / Q000627:therapeutic use; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*; D000070857:Walk Test
chemical_list: D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D000068581:Tadalafil; D011464:Epoprostenol; C427248:treprostinil
keywords: age; outcomes; pulmonary arterial hypertension; pulmonary hypertension
references.citation: J Am Coll Cardiol. 2010 May 4;55(18):1915-22
references.pmid: 20430262
references.citation: JAMA. 2007 Mar 14;297(10):1118-21
references.pmid: 17356034
references.citation: Respir Med. 2006 Apr;100(4):658-65
references.pmid: 16229997
references.citation: Am J Respir Crit Care Med. 2013 Aug 1;188(3):365-9
references.pmid: 23600433
references.citation: J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D42-50
references.pmid: 24355641
references.citation: Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1384-7
references.pmid: 9817683
references.citation: Am J Respir Crit Care Med. 2012 Oct 15;186(8):790-6
references.pmid: 22798320
references.citation: J Sci Med Sport. 2012 May;15(3):259-65
references.pmid: 22154397
references.citation: Chest. 2015 Jan;147(1):188-97
references.pmid: 25122150
references.citation: Am J Respir Crit Care Med. 2014 Feb 1;189(3):345-55
references.pmid: 24484330
references.citation: Ann Intern Med. 1987 Aug;107(2):216-23
references.pmid: 3605900
references.citation: Heart Lung Circ. 2015 Jul;24(7):719-23
references.pmid: 25790775
references.citation: Circulation. 2009 Jun 9;119(22):2894-903
references.pmid: 19470885
references.citation: Eur Respir J. 2006 Dec;28(6):1195-203
references.pmid: 16899485
references.citation: Chest. 2012 Dec;142(6):1383-90
references.pmid: 22628490
references.citation: Circ Heart Fail. 2011 May;4(3):257-65
references.pmid: 21411741
references.citation: Chest. 2014 Jul;146(1):159-66
references.pmid: 24480915
references.citation: Circulation. 2007 Apr 17;115(15):1982-90
references.pmid: 17404159
references.citation: Rheumatology (Oxford). 2006 Oct;45 Suppl 3:iii11-3
references.pmid: 16987822
references.citation: Natl Vital Stat Rep. 2014 Nov;63(7):1-63
references.pmid: 25383611
references.citation: Chest. 2013 Sep;144(3):952-8
references.pmid: 23669822
references.citation: Chest. 2007 Jan;131(1):94-100
references.pmid: 17218561
references.citation: Lupus. 2005;14(9):713-7
references.pmid: 16218473
references.citation: Circulation. 2013 Feb 5;127(5):624-33
references.pmid: 23307827
references.citation: J Heart Lung Transplant. 2010 Feb;29(2):137-49
references.pmid: 20022264
references.citation: Eur Respir Rev. 2012 Mar 1;21(123):8-18
references.pmid: 22379169
references.citation: Int J Cardiol. 2013 Sep 30;168(2):871-80
references.pmid: 23164592
references.citation: J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D51-9
references.pmid: 24355642
references.citation: Chest. 2011 Jan;139(1):128-37
references.pmid: 20558556
references.citation: Am J Respir Crit Care Med. 2002 Mar 15;165(6):800-4
references.pmid: 11897647