Abstract
It is widely known that the incidence of pulmonary arterial hypertension (PAH) is higher in female, whereas prognosis is poorer in male patients. However, sex differences in hemodynamic response to and long-term prognosis with PAH-targeted treatment in the modern era remain to be fully elucidated. We examined the long-term prognosis of 129 consecutive PAH patients (34 males and 95 females) diagnosed in our hospital from April 1999 to October 2014, and assessed hemodynamic changes in response to PAH-targeted therapy. Female patients had better 5-year survival compared with male patients (74.0 vs. 53.4%, P = 0.003); however, higher age quartiles in females were associated with poor outcome. Follow-up examination after medical treatment showed significant decreases in mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and pulmonary arterial capacitance (PAC) in both sexes (both P < 0.05), whereas only females had a significant improvement in right ventricular end-diastolic pressure (RVEDP), right atrial pressure (RAP), cardiac index, and mixed venous oxygen saturation (SvO2) (all P < 0.05). Baseline age significantly correlated with the hemodynamic changes only in female patients; particularly, there were significant sex interactions in RVEDP and RAP (both P < 0.10). The multivariable analysis showed that SvO2 at baseline and mPAP and SvO2 at follow-up were significant prognostic factors in males, whereas the changes in mPAP, PVR, and PAC and use of endothelin-receptor antagonist in females. These results indicate that female PAH patients have better long-term prognosis than males, for which better improvements of right ventricular functions and hemodynamics may be involved.
Highlights
Pulmonary arterial hypertension (PAH) is a disease characterized by progressive pulmonary vascular remodeling that increases pulmonary arterial pressure and leads to right heart failure and premature death [1]
The novel findings of the present study are as follows: (1) event-free survival at 5 years in Japanese PAH patients was 68.5%, where female patients had superior survival compared with male patients, (2) aging was significantly associated with poor outcome in females but not in males, (3) in response to optimal medical therapy, several parameters, right ventricular end-diastolic pressure (RVEDP) and right atrial pressure (RAP), were ameliorated in females but not in males, where significant sex interactions were noted in terms of the correlation between age and the changes in RVEDP and RAP, (4) significant prognostic factors were hemodynamics at baseline and follow-up in males but were hemodynamic changes in females, and (5) the uses of endothelin-receptor antagonists (ERAs) and phosphodiesterase type-5 (PDE-5) inhibitor were related to better prognosis in females but not in males
Recent registry studies of IPAH patients showed that males had higher mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and RAP, and lower cardiac index (CI) at diagnosis [9, 10, 15], no significant sex differences were noted in the present study
Summary
Pulmonary arterial hypertension (PAH) is a disease characterized by progressive pulmonary vascular remodeling that increases pulmonary arterial pressure and leads to right heart failure and premature death [1]. Heart and Vessels (2018) 33:939–947 prognostic factors of PAH [7, 11,12,13] These clinical parameters of RV functions are be poorer in male PAH patients at diagnosis [10, 14, 15]. Sex differences in the relationship between hemodynamic parameters and longterm prognosis after PAH-specific therapy remain to be elucidated. This point is important when developing personalized medicine by sex for each PAH patient. We examined sex differences in the hemodynamic responses to and long-term prognosis with PAH-specific medical therapy in PAH patients.
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