Abstract
To investigate the association between altered sex hormone expression and long-term right ventricular (RV) adaptation and progression of right heart failure in a Dutch cohort of Pulmonary Arterial Hypertension (PAH)-patients across a wide range of ages. In this study we included 279 PAH-patients, of which 169 females and 110 males. From 59 patients and 21 controls we collected plasma samples for sex hormone analysis. Right heart catheterization (RHC) and/or cardiac magnetic resonance (CMR) imaging was performed at baseline. For longitudinal data analysis, we selected patients that underwent a RHC and/or CMR maximally 1.5 years prior to an event (death or transplantation, N=49). Dehydroepiandrosterone-sulfate (DHEA-S) levels were reduced in male and female PAH-patients compared to controls, whereas androstenedione and testosterone were only reduced in female patients. Interestingly, low DHEA-S and high testosterone levels were correlated to worse RV function in male patients only. Subsequently, we analyzed prognosis and RV adaptation in females stratified by age. Females ≤45years had best prognosis in comparison to females ≥55years and males. No differences in RV function at baseline were observed, despite higher pressure-overload in females ≤45years. Longitudinal data demonstrated a clear distinction in RV adaptation. Although females ≤45years had an event at a later time point, RV function was more impaired at end-stage disease. Sex hormones are differently associated with RV function in male and female PAH-patients. DHEA-S appeared to be lower in male and female PAH-patients. Females ≤45years could persevere pressure-overload for a longer time, but had a more severe RV phenotype at end-stage disease.
Highlights
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by narrowing of pulmonary arterioles and right heart failure[1,2,3]
Pulmonary Arterial Hypertension (PAH)-induced sex differences in survival, right ventricular (RV) function and adaptation We included 236 idiopathic PAH, 33 hereditable PAH, 9 drug- and toxin-induced PAH and 1 PAH patient associated with HIV-infection, resulting in 110 male and 169 female patients in total in the age-stratified PAH cohort (N=279) (Figure 1)
Low DHEA-S and high testosterone levels associated with worse RV function in male PAH To investigate the association of RV adaptation and sex hormones, we quantified plasma levels of sex hormones in a subgroup of patients
Summary
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by narrowing of pulmonary arterioles and right heart failure[1,2,3]. The majority of data is cross-sectional or at one point in time during the disease course, whereas longitudinal data of RV function during progression towards right heart failure is pivotal to understand differential RV adaptation patterns between male and female patients. In this study we aimed to investigate the association between altered sex hormone expression levels and RV adaptation and to assess progression of right heart failure over time in a Dutch cohort of patients with a wide range of ages. To investigate the association between altered sex hormone expression and long-term right ventricular (RV) adaptation and progression of right heart failure in a Dutch cohort of Pulmonary Arterial Hypertension (PAH)-patients across a wide range of ages
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