PMID- 36053665
OWN - NLM
STAT- MEDLINE
DCOM- 20230103
LR  - 20240302
IS  - 2325-6621 (Electronic)
IS  - 2329-6933 (Print)
IS  - 2325-6621 (Linking)
VI  - 20
IP  - 1
DP  - 2023 Jan
TI  - Baseline Sex Differences in Pulmonary Arterial Hypertension Randomized Clinical 
      Trials.
PG  - 58-66
LID - 10.1513/AnnalsATS.202203-207OC [doi]
AB  - Rationale: Sex-based differences in pulmonary arterial hypertension (PAH) are 
      known, but the contribution to disease measures is understudied. Objectives: We 
      examined whether sex was associated with baseline 6-minute-walk distance (6MWD), 
      hemodynamics, and functional class. Methods: We conducted a secondary analysis of 
      participant-level data from randomized clinical trials of investigational PAH 
      therapies conducted between 1998 and 2014 and provided by the U.S. Food and Drug 
      Administration. Outcomes were modeled as a function of an interaction between sex 
      and age or sex and body mass index (BMI), respectively, with generalized mixed 
      modeling. Results: We included a total of 6,633 participants from 18 randomized 
      clinical trials. A total of 5,197 (78%) were female, with a mean age of 49.1 
      years and a mean BMI of 27.0 kg/m(2). Among 1,436 males, the mean age was 49.7 
      years, and the mean BMI was 26.4 kg/m(2). The most common etiology of PAH was 
      idiopathic. Females had shorter 6MWD. For every 1 kg/m(2) increase in BMI for 
      females, 6MWD decreased 2.3 (1.6-3.0) meters (P < 0.001), whereas 6MWD did not 
      significantly change with BMI in males (0.31 m [-0.30 to 0.92]; P = 0.32). 
      Females had lower right atrial pressure (RAP) and mean pulmonary artery pressure, 
      and higher cardiac index than males (all P < 0.03). Age significantly modified 
      the sex by RAP and mean pulmonary artery pressure relationships. For every 
      10-year increase in age, RAP was lower in males (0.5 mm Hg [0.3-0.7]; P < 0.001), 
      but not in females (0.13 [-0.03 to 0.28]; P = 0.10). There was a significant 
      decrease in pulmonary vascular resistance (PVR) with increasing age regardless of 
      sex (P < 0.001). For every 1 kg/m(2) increase in BMI, there was a 3% decrease in 
      PVR for males (P < 0.001), compared with a 2% decrease in PVR in females 
      (P < 0.001). Conclusions: Sexual dimorphism in subjects enrolled in clinical 
      trials extends to 6MWD and hemodynamics; these relationships are modified by age 
      and BMI. Sex, age, and body size should be considered in the evaluation and 
      interpretation of surrogate outcomes in PAH.
FAU - Ventetuolo, Corey E
AU  - Ventetuolo CE
AD  - Department of Medicine.
AD  - Department of Health Services, Policy, and Practice, School of Public Health, 
      and.
FAU - Moutchia, Jude
AU  - Moutchia J
AD  - Department of Biostatistics, Epidemiology, and Informatics and.
FAU - Baird, Grayson L
AU  - Baird GL
AD  - Department of Diagnostic Imaging, Alpert Medical School, Brown University, 
      Providence, Rhode Island.
AD  - Lifespan Hospital System, Providence, Rhode Island.
FAU - Appleby, Dina H
AU  - Appleby DH
AD  - Department of Biostatistics, Epidemiology, and Informatics and.
FAU - McClelland, Robyn L
AU  - McClelland RL
AD  - Department of Biostatistics, University of Washington School of Public Health, 
      Seattle, Washington; and.
FAU - Minhas, Jasleen
AU  - Minhas J
AUID- ORCID: 0000-0001-7864-6096
AD  - Department of Biostatistics, Epidemiology, and Informatics and.
FAU - Min, Jeff
AU  - Min J
AD  - Department of Biostatistics, Epidemiology, and Informatics and.
FAU - Holmes, John H
AU  - Holmes JH
AD  - Department of Medicine, Perelman School of Medicine at the University of 
      Pennsylvania, Philadelphia, Pennsylvania.
FAU - Urbanowicz, Ryan J
AU  - Urbanowicz RJ
AD  - Department of Medicine, Perelman School of Medicine at the University of 
      Pennsylvania, Philadelphia, Pennsylvania.
FAU - Al-Naamani, Nadine
AU  - Al-Naamani N
AD  - Department of Biostatistics, Epidemiology, and Informatics and.
AD  - Department of Biostatistics, University of Washington School of Public Health, 
      Seattle, Washington; and.
FAU - Kawut, Steven M
AU  - Kawut SM
AD  - Department of Biostatistics, Epidemiology, and Informatics and.
AD  - Department of Medicine, Perelman School of Medicine at the University of 
      Pennsylvania, Philadelphia, Pennsylvania.
LA  - eng
GR  - K23 HL141584/HL/NHLBI NIH HHS/United States
GR  - K24 HL103844/HL/NHLBI NIH HHS/United States
GR  - R01 HL141268/HL/NHLBI NIH HHS/United States
GR  - T32 HL007891/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Am Thorac Soc
JT  - Annals of the American Thoracic Society
JID - 101600811
SB  - IM
MH  - Humans
MH  - Female
MH  - Male
MH  - Middle Aged
MH  - *Pulmonary Arterial Hypertension
MH  - Sex Characteristics
MH  - *Hypertension, Pulmonary
MH  - Randomized Controlled Trials as Topic
MH  - Familial Primary Pulmonary Hypertension
MH  - Hemodynamics
PMC - PMC9819259
OTO - NOTNLM
OT  - body mass index
OT  - pulmonary arterial hypertension
OT  - sex
OT  - sexual dimorphism
EDAT- 2022/09/03 06:00
MHDA- 2023/01/04 06:00
PMCR- 2024/01/01
CRDT- 2022/09/02 11:54
PHST- 2022/09/03 06:00 [pubmed]
PHST- 2023/01/04 06:00 [medline]
PHST- 2022/09/02 11:54 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - 10.1513/AnnalsATS.202203-207OC [doi]
PST - ppublish
SO  - Ann Am Thorac Soc. 2023 Jan;20(1):58-66. doi: 10.1513/AnnalsATS.202203-207OC.