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[Preprint]. 2024 Apr 27:2024.04.25.24306398. [Version 1] doi: 10.1101/2024.04.25.24306398

Sex Differences in Pulmonary Hypertension and Associated Right Ventricular Dysfunction

Janet I Ma, Ndidi Owunna, Nona M Jiang, Xiaodan Huo, Emily Zern, Jenna N McNeill, Emily S Lau, Eugene Pomerantsev, Michael H Picard, Dongyu Wang, Jennifer E Ho
PMCID: PMC11071572  PMID: 38712108

ABSTRACT

Background

Prior studies have established the impact of sex differences on pulmonary arterial hypertension (PAH). However, it remains unclear whether these sex differences extend to other hemodynamic subtypes of pulmonary hypertension (PH).

Methods

We examined sex differences in PH and hemodynamic PH subtypes in a hospital-based cohort of individuals who underwent right heart catheterization between 2005-2016. We utilized multivariable linear regression to assess the association of sex with hemodynamic indices of RV function [PA pulsatility index (PAPi), RV stroke work index (RVSWI), and right atrial: pulmonary capillary wedge pressure ratio (RA:PCWP)]. We then used Cox regression models to examine the association between sex and clinical outcomes among those with PH.

Results

Among 5208 individuals with PH (mean age 64 years, 39% women), there was no significant sex difference in prevalence of PH overall. However, when stratified by PH subtype, 31% of women vs 22% of men had pre-capillary (P<0.001), 39% vs 51% had post-capillary (P=0.03), and 30% vs 27% had mixed PH (P=0.08). Female sex was associated with better RV function by hemodynamic indices, including higher PAPi and RVSWI, and lower RA:PCWP ratio (P<0.001 for all). Over 7.3 years of follow-up, female sex was associated with a lower risk of heart failure hospitalization (HR 0.83, CI 95% CI 0.74– 0.91, p value <0.001).

Conclusions

Across a broad hospital-based sample, more women had pre-capillary and more men had post-capillary PH. Compared with men, women with PH had better hemodynamic indices of RV function and a lower risk of HF hospitalization.

CLINICAL PERSPECTIVE

  1. What Is New?
    • Although sex differences have been explored in pulmonary arterial hypertension, sex differences across pulmonary hypertension (PH) in broader samples inclusive of all hemodynamic subtypes remain less well defined
    • We delineate sex differences in hemodynamic subtypes of PH and associated right ventricular function in a large, heterogenous, hospital-based sample of individuals who underwent right heart catheterization
    • Sex has a significant impact on prevalence of PH across hemodynamic subtypes as well as associated RV function
  2. What Are the Clinical Implications?
    • Understanding sex differences across different PH hemodynamic subtypes is paramount to refining risk stratification between men and women
    • Further elucidating sex differences in associated RV function and clinical outcomes may aid in developing sex-specific therapies or management strategies to improve clinical outcomes

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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