TY - JOUR
T1 - Interplay of sex hormones and long-term right ventricular adaptation in a Dutch PAH-cohort
AU - van Wezenbeek, Jessie
AU - Groeneveldt, Joanne A
AU - Llucià-Valldeperas, Aida
AU - van der Bruggen, Cathelijne E
AU - Jansen, Samara M A
AU - Smits, A Josien
AU - Smal, Rowan
AU - van Leeuwen, Joost W
AU - Remedios, Cris Dos
AU - Keogh, Anne
AU - Humbert, Marc
AU - Dorfmüller, Peter
AU - Mercier, Olaf
AU - Guignabert, Christophe
AU - Niessen, Hans W M
AU - Handoko, M Louis
AU - Marcus, J Tim
AU - Meijboom, Lilian J
AU - Oosterveer, Frank P T
AU - Westerhof, Berend E
AU - Heijboer, Annemieke C
AU - Bogaard, Harm Jan
AU - Vonk Noordegraaf, Anton
AU - Goumans, Marie José
AU - de Man, Frances S
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/4
Y1 - 2022/4
N2 - BACKGROUND: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.
AB - BACKGROUND: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.
KW - Familial Primary Pulmonary Hypertension
KW - Female
KW - Gonadal Steroid Hormones
KW - Heart Ventricles/diagnostic imaging
KW - Humans
KW - Male
KW - Pulmonary Arterial Hypertension
KW - Ventricular Dysfunction, Right
KW - Ventricular Function, Right
U2 - 10.1016/j.healun.2021.11.004
DO - 10.1016/j.healun.2021.11.004
M3 - Article
C2 - 35039146
SN - 1053-2498
VL - 41
SP - 445
EP - 457
JO - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
IS - 4
ER -