Biological Sex Differences in the US-CTEPH-R

Authors

• Meghan M. Cirulis, Intermountain Health
• William R. Auger, University of California - San Diego
• Raymond L. Benza, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Richard N. Channick, David Geffen School of Medicine, UCLA
• Kelly Chin, UT Southwestern
• Duane Davis, Adventhealth
• C. Greg Elliott, Intermountain Health
• Feng He, University of California
• Sonia Jain, University of California
• Andrea Z. LaCroix, University of California
• Michael M. Madani, University of California
• Valerie McLaughlin, University of Michigan Medical School, Ann Arbor, MI
• Victor Tapson, Cedars-Sinai Medical Center
• Kim Kerr, University of California
• Corey E. Ventetuolo, Brown University

ORCID

0000-0001-9627-6236 (Benza)

Document Type

Article

Publication Date

2026

DOI

10.1093/annalsats/aaoag098

Publication Title

Annals of the American Thoracic Society

Volume

Advance online publication

Pages

26 pp.

Abstract

Rationale

Biological sex underpins phenotypic differences in many cardiopulmonary conditions. In pulmonary hypertension, most studies have focused on the 'sex paradox' in pulmonary arterial hypertension, where females are more susceptible to PAH but have better right ventricular function, better response to PAH medications, and better survival than males. Sex differences have also been observed in chronic thromboembolic pulmonary hypertension (CTEPH) but are less well characterized.

Objective(s)

To investigate sex differences in males and females diagnosed with CTEPH in the United States.

Methods

Using the multicenter United States CTEPH Registry, we explored sex differences in a CTEPH population at baseline and follow-up. We collected data every six months for a total of 48 months. Sex was determined from self-reported "male", "female", or "transgender" categories recorded on case report forms. We report descriptive analyses comparing male and female characteristics. We examined prespecified variables of interest using regression modeling, including adjustment for age, body mass index (BMI) and interaction terms (sex vs age, sex vs BMI). Survival analysis was performed with Cox proportional hazards modeling.

Results

Females (n = 367, 49.1%) had greater BMI than males (Median [IQR] F: 32 kg/m2 [26.6, 38.8] v. M: 28.7 kg/m2 [25.5, 33.8]). Males were more likely to have a recognized history of acute deep vein thrombosis (OR 2.6; CI 1.9-3.5). Males had better baseline PH-specific health-related quality of life (HRQoL) by EmPHasis10 (-3.3; CI -5.0- (-1.7), World Health Organization functional class (FC III/IV OR 0.52, CI 0.37-0.74) and longer six-minute walk distance (+82.3 m, CI 56.4-108.2). Males were less likely to have distally located disease (OR 0.53, CI 0.35-0.78) and were less likely to have inoperable CTEPH (OR 0.62, CI 0.40-0.96). Post-PTE, females had persistently worse HRQoL and function, with increased need for adjunctive therapies. There was no difference in overall survival between males and females (HR 1.11; CI 0.71-1.75).

Conclusion

Males and females may have distinct CTEPH phenotypes which impact access to and feasibility of PTE. There are sex-associated disparities in the experience of CTEPH as a disease state, and differential impacts on HRQoL that warrant further investigation.

Rights

Copyright © 2026 Oxford University Press, on behalf of the American Thoracic Society. All rights reserved.

Included in accordance with publisher policy.

Comments

This is the accepted version of the manuscript and may differ from the published version of record.

Original Publication Citation

Cirulis, M. M., Auger, W. R., Benza, R. L., Channick, R. N., Chin, K., Davis, R. D., Elliott, C. G., He, F., Jain, S., LaCroix, A. Z., Madani, M. M., McLaughlin, V., Tapson, V., Kerr, K., & Ventetuolo, C. E. (2026). Biological sex differences in the US-CTEPH-R. Annals of the American Thoracic Society. Advance online publication. https://doi.org/10.1093/annalsats/aaoag098

Repository Citation

Cirulis, M. M., Auger, W. R., Benza, R. L., Channick, R. N., Chin, K., Davis, R. D., Elliott, C. G., He, F., Jain, S., LaCroix, A. Z., Madani, M. M., McLaughlin, V., Tapson, V., Kerr, K., & Ventetuolo, C. E. (2026). Biological sex differences in the US-CTEPH-R. Annals of the American Thoracic Society. Advance online publication. https://doi.org/10.1093/annalsats/aaoag098