Sex Differences in Pulmonary Hypertension and Associated Right Ventricular Dysfunction

Abstract

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).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. Among 5208 individuals with PH (mean age 64 years, 39% women), there was no significant sex difference in prevalence of PH. However, when stratified by PH subtype, 31% of women vs 22% of men had precapillary (P<0.001), 39% vs 51% had postcapillary (P<0.001), and 30% vs 27% had mixed PH (P=0.15). Female sex was associated with better RV function by hemodynamic indices, including higher PAPi and RVSWI (P<0.001 for both). 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 <0.001). In conclusion, across a broad hospital-based sample, more women had precapillary and more men had postcapillary PH. Compared with men, women with PH had better hemodynamic indices of RV function and a lower risk of HF hospitalization.

INTRODUCTION

Pulmonary hypertension (PH) is a heterogenous disease associated with poor clinical outcomes (1). While clinically PH is classified by World Health Organization groups based on etiology, grouping by hemodynamic assessment into precapillary PH, postcapillary PH, and mixed pre- and postcapillary PH, carries significant prognostic and therapeutic implications, particularly for those with a precapillary component (1). In addition, one of the strongest predictors of mortality in this patient population is RV dysfunction, a frequent long-term consequence of PH associated with poor prognosis (2).

Sex differences have long been observed in pulmonary arterial hypertension (PAH), a subset of PH with precapillary hemodynamic characteristics. Specifically, PAH has a higher prevalence in women compared with men, and yet men appear to have worse RV function and survival (3). The etiology of these differences remains unclear, but some have postulated that sex hormones such as higher levels of estrogen may be responsible for both the increased risk women face in developing PAH as well as their improved RV function and survival compared with men (3).

Despite the extensive study of sex differences in prevalence and clinical trajectory of PAH, little is known about sex differences across other hemodynamic PH subtypes. In this context, we sought to study sex differences in PH prevalence, associated RV dysfunction, and clinical outcomes across a broad and clinically heterogeneous hospital-based sample of individuals undergoing right heart catheterization (RHC). Based current knowledge of PAH, we hypothesized that 1) women would have a higher prevalence of precapillary PH compared with men, which would not persist across other hemodynamic subtypes, and 2) across all hemodynamic PH subtypes, women would demonstrate better RV function and clinical outcomes compared with men.

METHODS

Study Sample

Our study examined ambulatory and hospitalized patients who underwent RHC between 2005 and 2016 at Massachusetts General Hospital. If an individual underwent multiple RHC procedures during this period, only the initial RHC was included for analysis. A total of 10,306 cases were included. Cases were excluded if they met the following clinical exclusion criteria: acute myocardial infarction (MI) occurring on the same day as catheterization, cardiac arrest or shock within 24 hours, presence of mechanical ventilation, presence of intra-aortic balloon pump, history of heart or lung transplant, complicated adult congenital heart disease, history of valvular replacement, or those on dialysis (n=887). Cases were also excluded if there were missing key clinical covariates (n=484), patient identifier variables (n=398), or hemodynamic parameters (n=252), which led to a final study sample of 8285 cases. This study was approved by the appropriate Institutional Review Board.

Clinical, PH, and RV hemodynamic variables

The following clinical characteristics were extracted from the medical record at the time of RHC: age, sex, body mass index (BMI), smoking status, and presence of comorbidities (diabetes mellitus, hypertension, history of MI, history of heart failure (HF), prior lung disease, and chronic kidney disease). Obstructive sleep apnea (OSA) was ascertained from the electronic medical record utilizing International Classification of Diseases Ninth Revision (ICD-9) or Tenth Revision (ICD-10) codes.

Hemodynamic measures were recorded directly from the time of RHC, including resting blood pressure, heart rate, mean right atrial (RA) pressure, pulmonary artery (PA) systolic and diastolic pressure, trans-pulmonary gradient (TPG), and mean pulmonary capillary wedge pressure (PCWP). Any non-physiologic parameters were set to missing. The PA pulsatility index (PAPi) was calculated as $\frac{PAsystolic-PAdiastolicpressure}{RApressure}$. If RA pressure was recorded as zero, the value was set to 1 to allow for PAPi calculation. If RA pressure was recorded as negative, this was deemed non-physiologic and set to missing, which affected <1% of measurements. Cardiac output and index measurements were obtained via thermodilution methods whenever possible. If not available, assumed Fick cardiac output and index were used. Both were indexed using the Mosteller formula for body surface area [7]. Right ventricular stroke work index (RVSWI) was calculated as 0.0136 x stroke volume index x (Mean PA pressure -mean RA pressure), where stroke volume index was calculated by dividing cardiac index by heart rate.

PH was defined as mean PA pressure (mPAP) >20 mmHg based on the 2022 European Society of Cardiology/European Respiratory Society guidelines (1). We further categorized PH into three hemodynamic subtypes: precapillary PH (TPG >12 mmHg and PCWP ≤ 15 mmHg), postcapillary PH (TPG ≤ 12 mmHg and PCWP > 15 mmHg), and mixed PH (TPG > 12 mmHg and PCWP > 15 mmHg). We utilized TPG cutpoints rather than pulmonary vascular resistance (PVR) as not all participants had available cardiac output. For those with cardiac output data, we examined PH hemodynamic subtypes using PVR instead of TPG in secondary analyses.

Clinical Outcomes

Primary clinical outcomes included all-cause mortality and HF hospitalization. All-cause mortality was ascertained using the National Social Security Death Master Index and hospital records, abstracted on 06/10/2020. Due to confidentiality purposes, the precise dates of deaths that occurred between 06/10/2017 and the date of abstraction are protected nationally. Time-to-event analyses were conducted by imputing death dates at the midpoint of the blanking period (12/10/2018).

HF hospitalizations were defined using an ICD-9 or ICD-10 code for HF as the primary discharge diagnosis or a current procedural terminology code for heart transplantation or durable ventricular assist device. The follow-up period for each participant was defined as time from RHC to death date or date of final encounter in the electronic health record. Patients were censored based on time of last encounter.

Statistical Analysis

The distribution of PAPi was winsorized to limit effect of outliers on the analysis, setting the minimum at 0.3 and the maximum at 30 (2 patients had PAPi < 0.3, and 51 patients had PAPi > 30 prior to winsorizing). Baseline characteristics among those with PH were summarized across the total sample by sex. Sex differences in prevalence of PH and PH subtypes were examined using Chi squared tests. We examined cross-sectional associations of sex with hemodynamic indices of RV function among those with PH, including PAPi, RVSWI, and RA:PCWP ratio using multivariable linear regression. Models were adjusted for the following clinical covariates: age, BMI, hypertension, diabetes mellitus, OSA, chronic lung disease, prevalent MI, prevalent HF, chronic kidney disease.

We next constructed multivariable Cox models to examine the association of sex with outcomes, adjusting for covariates as above. In secondary models, we stratified by PH hemodynamic subtype. In exploratory analyses, we evaluated whether sex modified the association of RV function with adverse outcomes among those with PH using multiplicative interaction terms (sex*PAPi, sex*RVSWI, and sex*RA:PCWP ratio). Analyses were conducted using SAS software, Version 9.4 (Cary, North Carolina, USA).

RESULTS

Sex differences in prevalence of PH and hemodynamic subtypes

Among 8285 individuals who underwent right heart catheterization between 2005-2016, 5208 (63%) met criteria for PH, as defined by a mPAP >20 mmHg. There was no significant sex difference in the prevalence of overall PH, with 2032 (62%) women and 3176 (63%) men meeting PH criteria (P=0.96, baseline characteristics in Supplemental Table 1).

Among individuals with PH, average age was 64±12 years and 39% were women. Men were significantly more likely to have comorbid conditions including previous MI, previous HF, hypertension, diabetes mellitus, hypercholesteremia, and OSA (p<0.001 for all). However, women were more likely to have chronic lung disease (20.2% vs 16.7%, p<0.001). Additional baseline characteristics of individuals with PH are shown in Table 1.

Table 1.

Clinical characteristics of men and women with PH, n= 5208

	Men (n =3176)	Women (n=2032)	p-value
Clinical Characteristics
Age, years	64 ± 12	64 ± 12	0.04
Race, n (%)			0.47
Asian	63 (2.0)	48 (2.4)
Black	150 (4.7)	106 (5.2)
Hispanic	93 (2.9)	68 (3.3)
Unknown	195 (6.1)	138 (6.8)
White	2675 (84.2)	1672 (82.3)
BMI, kg/m2	30.0 ± 6.5	30.5 ± 8.4	<0.001
Current smoker, n (%)	210 (6.6)	113 (5.6)	0.03
Previous kidney disease, n (%)	144 (4.5)	57 (2.8)	<0.001
Diabetes Mellitus, n (%)	922 (29.0)	479 (23.6)	<0.001
Hypertension, n (%)	2045 (64.4)	1105 (54.4)	<0.001
Hypercholesterolemia, n (%)	2090 (65.8)	1084 (53.3)	<0.001
Chronic lung disease, n (%)	531 (16.7)	410 (20.2)	<0.001
OSA, n (%)	588 (18.5)	280 (13.8)	<0.001
Previous MI, n (%)	829 (26.1)	250 (12.3)	<0.001
Previous HF, n (%)	1367 (43.0)	690 (34.0)	<0.001
Previous valvular disease, n (%)	1150 (36.2)	734 (36.1)	0.14
NT pro BNP, pg/mL)	2344 [831 - 5592]	2085 [747 - 5217]	0.05
Hemoglobin, g/dL	12.9 ± 2.3	12.2 ± 2.3	<0.001
Hemodynamics
Heart rate, bpm	74 ± 16	76 ± 16	<0.001
Systolic blood pressure, mmHg	122 [106 - 140]	133 [116 - 153]	<0.001
Mean arterial pressure, mmHg	85 [76 - 95]	88 [78 - 98]	<0.001
PA Systolic Pressure, mmHg	44 [37 - 55]	45 [37 - 55]	0.30
PA diastolic pressure, mmHg	19 [15 - 25]	19 [14 - 2]	0.06
Mean RA pressure, mmHg	9 [6 - 13]	8 [6 -12]	<0.001
Mean PCWP, mmHg	19 [14 - 24]	17 [13 - 22]	<0.001
TPG, mmHg	10 [7 - 15]	12 [9 - 17]	<0.001
PVR, Woods Units (WU)	2.05 [1.4 - 3.1]	2.5 [1.7 - 3.8]	<0.001
PAPi	2.9 [1.9 - 4.4]	3.25 [2.2 - 5.1]	<0.001
RVSWI, gm-m/m2/beat	9.4 [7.1 - 12.6]	10.2 [7.6 −13.6]	<0.001
RA pressure: PCWP ratio	0.5 [0.4 - 0.7]	0.5 [0.4 - 0.7]	0.36
Thermo cardiac output, L/min	5.0 [4.2 - 6.2]	4.7 [3.8 - 5.8]	<0.001
Thermo cardiac index, L/min/m2	2.4 [2.0 - 2.9]	2.6 [2.2 - 3.2]	<0.001

Table displays mean ± standard deviation and median [interquartile range]. Variable abbreviations: OSA (obstructive sleep apnea), MI (myocardial infarction), HF (heart failure), NT pro-bnp (N-terminal pro-B type natriuretic peptide), PA (Pulmonary artery), RA (Right arterial), PCWP (Pulmonary capillary wedge pressure), TPG (Transpulmonary pressure gradient), PVR (Peripheral vascular resistance), PAPi (Pulmonary artery pulsatility index), RVSWI (RV stroke work index).

We found that hemodynamic PH subtypes significantly differed by sex, with women more likely to have precapillary PH and men more likely to have postcapillary PH (Figure 1). Specifically, 31% of women vs 22% of men had precapillary PH (p<0.001), 39% vs 51% had postcapillary PH (p<0.001), and 30% vs 27% had mixed PH (p=0.08).

Figure 1.

Prevalence of hemodynamic PH subtypes in women (red) and men (blue). Among women with PH, 31% (n = 544) had precapillary PH, 39% had postcapillary PH (n = 685), and 30% had mixed (n = 527). Among women with PH, 22% (n = 605) had precapillary PH, 51% had postcapillary PH (n = 1402), and 27% had mixed (n = 743). Note that total individuals of PH in our study was 5208 (vs 4506 noted here); individuals who did not meet criteria for either precapillary, postcapillary, or mixed PH were excluded in assessing prevalence of subtypes.

Sex differences in RV function among individuals with PH

Among individuals with PH, women had a higher PAPi (3.25, interquartile range [IQR] 2.2-5.1 vs 2.9, IQR 1.9-4.4 in men, p<0.001) and RVSWI (10.2, IQR 7.6-13.6 vs 9.4, IQR 7.1-12.6 in men, P<0.001) compared to men. RA:PCWP did not differ by sex. These sex differences persisted in adjusted analyses, which again demonstrated that female sex was associated with better RV function as ascertained by PAPi and RVSWI (Table 2). Specifically, women with PH had higher PAPi (β 0.18, SE 0.03, p <0.001) and higher RVSWI (β 0.17, SE 0.03, p <0.001).

Table 2.

Association of female sex with indices of RV Function in individuals with PH

Sample	Measures of RV Function	β-estimate	Standard Error	p-value
Overall PH	PAPi	0.18	0.03	<0.001
	RVSWI	0.17	0.03	<0.001
	RA:PCWP ratio	−0.03	0.01	0.05
Precapillary PH	PAPi	0.18	0.06	0.002
	RVSWI	0.10	0.05	0.05
	RA:PCWP ratio	−0.09	0.04	0.02
Combined PH	PAPi	0.12	0.04	0.01
	RVSWI	0.11	0.05	0.04
	RA:PCWP ratio	−0.03	0.03	0.30
Postcapillary PH	PAPi	0.06	0.04	0.12
	RVSWI	0.13	0.04	0.005
	RA:PCWP ratio	−0.03	0.02	0.23

β-Estimate represents standard deviation unit difference in RV outcome measure between women vs men. Multivariable adjusted model was adjusted for age, BMI, prior heart failure, hypertension, diabetes, OSA, chronic lung disease, previous MI, chronic kidney failure, and chronic heart failure history. Variable abbreviations: RA: PCWP Ratio (Right Atrial/Pulmonary capillary wedge pressure ratio), PAPi (pulmonary artery pulsatility index), RVSWI (RV stroke work index); PH, pulmonary hypertension.

Measures of RV function significantly differed by sex across PH hemodynamic subtypes. Among those with precapillary disease, women had a higher PAPi (β 0.18, SE 0.06, p=0.002), lower RA:PCWP (β −0.09, SE 0.04, p=0.02), with similar RVSWI ratio compared with men (Table 2). Among those with mixed PH, PAPi (β 0.12, SE 0.04, p=0.01) and RVSWI (β 0.11, SE 0.05, p=0.04) were significantly higher in women compared to men, with similar RA:PCWP ratio. Lastly, among those with postcapillary PH, RVSWI was significantly higher in women compared to men (β 0.13, SE 0.04, p =0.005), with no differences in PAPi and RA:PCWP ratio.

Sex differences in clinical outcomes for PH

We next examined the association of sex with clinical outcomes among individuals with PH. Over a median follow-up time of 7.3 years (IQR 4.2 – 10 years), 4023 individuals experienced HF hospitalizations (1625 among women, 2398 in men), with 3549 all-cause death events (1413 in women, 2136 in men).

In multivariable-adjusted analyses, we found that female sex was associated with 17% lower hazard of HF hospitalization (HR 0.83, 95% CI 0.74– 0.91, p <0.001). This was driven predominantly by individuals with postcapillary PH, where women with postcapillary PH were significantly less likely to experience HF hospitalization than men (HR 0.79, 95% CI 0.68-0.93, p = 0.007, Table 3, Figure 2), whereas no differences in HF hospitalization were observed among those with precapillary or mixed PH. We observed no sex differences in risk of mortality among PH overall (HR 0.92, 95% CI 0.84-1.00, p = 0.05), nor by PH subtype. In exploratory analyses, sex did not significantly modify the association of RV function measures and HF hospitalization or mortality.

Table 3.

Association of female sex with clinical outcomes in individuals with PH

Sample	Outcome	HR	95% CI	p-value
Overall PH	HF Hospitalization	0.83	0.74– 0.91	<0.001
	All-Cause Mortality	0.92	0.84 −1.00	0.05
Precapillary PH	HF Hospitalization	0.93	0.70-1.21	0.61
	All-Cause Mortality	0.90	0.75-1.08	0.25
Postcapillary PH	HF Hospitalization	0.79	0.68-0.93	0.007
	All-Cause Mortality	0.88	0.76-1.03	0.11
Mixed PH	HF Hospitalization	0.83	0.69-1.01	0.058
	All-Cause Mortality	0.88	0.75-1.03	0.10

Hazard ratios (HR) represent comparison of adverse PH outcomes in women when compared to men. Multivariable models were adjusted for age, sex, hypertension, diabetes mellitus, obstructive sleep apnea, chronic lung disease, prevalent myocardial infarction, prevalent HF. Abbreviations: CI, confidence interval; HR, hazard ratio; HF, heart failure; PH, pulmonary hypertension

Figure 2.

Association of sex with adverse outcomes including heart failure hospitalization and mortality in age-adjusted and multivariable analyses. Hazard ratio (HR) indicates risk in female vs male individuals. Multivariable models were adjusted for age, sex, hypertension, diabetes mellitus, obstructive sleep apnea, chronic lung disease, prevalent myocardial infarction, prevalent heart failure.

DISCUSSION

We examined sex differences in prevalence of PH, hemodynamic PH subtypes, measures of RV dysfunction, and clinical outcomes in a large hospital-based sample referred for RHC, representing a broad spectrum of cardiopulmonary disease. While prevalence of overall PH was similar among women and men, women were more likely to have precapillary PH while men were more likely to have postcapillary PH. Among individuals with PH, female sex was associated with better hemodynamic indices of RV function and lower risk of HF hospitalization. These findings build on a current body of literature that has thus far primarily explored sex differences in PAH, expanding our understanding to a much broader population encompassing all PH hemodynamic subtypes with potential implications for future sex-specific risk stratification and treatment in these groups.

Our findings regarding prevalence extend upon well-described sex differences in PAH, a subset of precapillary PH, where female sex has been established as a primary risk factor (3, 4). While prevalence of PAH is higher among women vs men, women with PAH demonstrate better RV function and overall clinical outcomes compared with men. A systematic review of 11 randomized trials found that women with PAH had lower RA pressure, higher cardiac index, and lower PVR compared with men (5). Similarly, a study by Kjellstrom et al examining sex differences in individuals with idiopathic PAH found that women were younger, had lower PVR, and fewer comorbidities than men (6). They found that while PAH was more prevalent in women, men had worse survival, although this difference was attenuated by age. Our findings somewhat differ in clinical outcomes when examining a broader group of individuals with PH across hemodynamic subtypes, where risk of HF hospitalization, but not mortality, was significantly higher for men compared with women in all-comers with PH.

Our findings regarding the predominant male prevalence in postcapillary PH is noteworthy. While our study cannot attribute exact etiology, this is likely in the setting of left-sided heart disease, where known sex differences also exist. For example, prior studies have demonstrated that men are more likely to develop HF with reduced ejection fraction (HFrEF), while women are more predisposed to HF with preserved ejection fraction (HFpEF) (7). While both HF subtypes have similarly wide ranges in estimated PH prevalence (40-73% for HFrEF, and 36-83% for HFpEF) (8–12), PH in HFpEF has been reported to occur more frequently in women (10). Our finding of male predominance in postcapillary PH is in keeping with the sex differences we found in prevalent HF amongst all individuals with PH, present in 43% of men, yet only 34% of women (p-value < 0.001).

In prior studies of sex differences in RV function, women appear to have better RV systolic function compared with men both in community-based samples without PH and among those with PAH (13, 14). For example, in the Multi-Ethnic Study of Atherosclerosis, a large prospective study examining both men and women without clinical cardiovascular disease who underwent cardiac MRI, men had higher RV mass and volumes while women had higher RV function (13). In PAH, women have been shown to have better RV function than men, also reflected in our results demonstrating a higher PAPI and lower RA:PCWP in women. In a small retrospective cohort study of 101 individuals with idiopathic PAH, sex differences in RV function were correlated with subsequent sex differences in response to treatment and survival (15). Although RV ejection fraction was found to be similar in both men and women at baseline, following initiation of treatment, there was a decline in men and increase in women despite comparable reductions in PVR. Men also had significantly worse transplant-free survival compared with women; a mediation analysis found 39% of this survival difference was mediated through changes in RVEF for both women and men after initiating PAH therapies.

Other types of PH have not been studied as extensively with respect to sex differences in RV function, although there is increasing interest in elucidating distinct phenotypes between men and women. In a retrospective study by Prins et al, male sex was the strongest predictor of RV dysfunction in group 3 PH, even after adjusting for PVR (16). Men with group 3 PH also showed a progressive decline in RV contractility with increasing PVR. Similarly, among individuals with HFrEF (LVEF <35%), men were nearly twice as likely to have concomitant RV dysfunction compared with women, despite similar LV ejection fraction (17). Among individuals with HFpEF, men were found to have worse RV function compared with women at every mPAP, with male sex again being an independent predictor of RV dysfunction (18). Our findings are in keeping with these prior studies, confirming a significant sex difference in RV dysfunction across all PH hemodynamic subtypes, with women demonstrating higher RV function compared with men in precapillary, postcapillary, and mixed PH.

The mechanisms underlying sex differences in RV dysfunction and PH remain unclear, although sex hormones are postulated to play an important role since cardiac myocytes express receptors for all major sex hormones (19). The “estrogen hypothesis,” that higher estrogen levels confer risk of PAH, yet are cardioprotective in the RV, has been touted as a possible mechanism. This has been tested across various preclinical models: in a rat model of PH, estrogen E2 appears to promote adverse pulmonary vascular remodeling but also demonstrate RV protective effects in vivo through decreased RV apoptopic signaling, pro-inflammatory cytokine expression, oxidative stress, and mitochondrial dysfunction (20–21). Other studies have demonstrated a direct role of E2 on the pulmonary vasculature, specifically increasing both proximal and distal pulmonary arterial compliance, which may have a downstream effect on RV remodeling and function (22–24). In humans, estrogen appears to favorably modulate RV function. In the MESA-Right Ventricle study which examined the role of sex hormones in individuals without clinical cardiovascular disease, Ventetuolo et al showed that post-menopausal women taking estradiol (an estrogen-based steroid hormone) for menopausal hormone therapy had higher RV ejection fraction compared with men (25). Recently, a randomized controlled trial of anastrozole vs placebo in postmenopausal women and men demonstrated increased circulating estradiol in the treatment group, yet no difference in 6-minute walk difference or N-terminal pro-B type natriuretic peptide compared to placebo. Importantly, there was also no decrement in RV function in the treatment group, demonstrating safety of therapeutic use (26). Given these results, further randomized controlled trials of premenopausal women are warranted.

Our study has several limitations worth noting. First, RHC allowed for diagnosis and hemodynamic subtyping of PH but not clinical categorization by WHO classification, and definitive etiology of PH was not possible to ascertain comprehensively. Second, we examined individuals undergoing clinically indicated RHC, which may have resulted in selection bias, and generalizability of our study findings needs to be interpreted in that context. Additionally, due to the observational study design, we acknowledge the possibility of residual confounding, and causal inferences regarding sex differences cannot be drawn.

Our study also exhibits several strengths, most notably the large sample size and detailed hemodynamic data from RHC in a broad population across all PH hemodynamic subtypes. One unique strength of our study is our use of hemodynamic indices of RV function rather than non-invasive assessment using echocardiography or MRI compared with prior studies. PAPi, RA:PCWP ratio, and RVSWI have all been correlated with clinical outcomes (27–29). Previous literature has also demonstrated PAPi may correlate more significantly to severe clinical RV failure in post-LVAD patients compared with echocardiographic-derived measurements, although this has not been as well-established in other clinical situations (30).

In sum, we found similar prevalence of overall PH among women and men, with women more likely to have precapillary PH while men were more likely to have postcapillary PH. Further, among individuals with PH, female sex was associated with better hemodynamic indices of RV function and lower risk of HF hospitalization. These findings extend prior studies predominantly focused on sex differences in PAH to a large and clinically heterogeneous hospital-based sample with invasive hemodynamic assessment. Our findings illustrate the growing need for future studies to better understand underlying mechanisms and sex-specific considerations in RV dysfunction and associated clinical outcomes for individuals across all PH subtypes, as they may have important implications for risk stratification and management.

Highlights.

• In a right heart catheterization sample, prevalence of PH was similar among women and men

• Precapillary PH was more common in women, and postcapillary PH more common in men.

• Women with PH have better hemodynamic indices of RV function and a lower risk of subsequent HF hospitalization

• Understanding sex differences across PH subtypes is paramount to sex-based risk stratification