Sex Differences in Pulmonary Hypertension and Associated Right Ventricular Dysfunction

BackgroundPrior 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). MethodsWe 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. ResultsAmong 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). ConclusionsAcross 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 PERSPECTIVEO_LIWhat Is New? O_LIAlthough 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 C_LIO_LIWe 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 C_LIO_LISex has a significant impact on prevalence of PH across hemodynamic subtypes as well as associated RV function C_LI C_LIO_LIWhat Are the Clinical Implications? O_LIUnderstanding sex differences across different PH hemodynamic subtypes is paramount to refining risk stratification between men and women C_LIO_LIFurther elucidating sex differences in associated RV function and clinical outcomes may aid in developing sex-specific therapies or management strategies to improve clinical outcomes C_LI C_LI