Sex differences in hemodynamic responses and long-term survival to optimal medical therapy in patients with pulmonary arterial hypertension

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.

Differential effects of integrin‐linked kinase inhibitor Cpd22 on severe pulmonary hypertension in male and female rats

“…Although developing more severe disease, male patients show less improvements of hemodynamics and right ventricular functions in response to current therapies, which is linked with worse overall long-term prognosis. 6 Our data, however, show that pharmacological inhibition of ILK with Cpd22 markedly attenuated pulmonary vascular remodeling, PH, and RV hypertrophy in males, which is in good agreement with our previous studies on male mice with SuHx-induced PH. 9 Female rats, treated with Cpd22, showed no significant decrease of pulmonary vascular remodeling, PH, RV hypertrophy, and RV EDP and did not improve RV contractility.…”

“…3 PAH is predominantly female disease. Male patients, however, develop more severe disease and respond poorer to current therapies, [4][5][6] suggesting that responses to novel anti-proliferative therapeutics could also be gender-dependent.…”

Pulmonary Artery Pressure as a Treatment Target to Improve the Prognosis of Idiopathic Pulmonary Arterial Hypertension ― Insight From a Cohort From Two Japanese Pulmonary Hypertension Centers ―

“…Utilization of this strategy had increased its use substantially all over Japan by approximately 2010, and several centers in Japan have reported that a reduction of mPAP was found to be related to improved prognosis. 8 , 14 NYHA and echocardiography data, the reported important diagnostic markers, were not included in this paper. The purpose of this study was to determine the treatment target for improving IPAH, and not to identify the factors related to prognosis.…”

At the X-Roads of Sex and Genetics in Pulmonary Arterial Hypertension

“…In idiopathic PAH at baseline, men have lower RV ejection fraction and stroke volume compared to age-matched females despite similar pulmonary artery pressure (PAP) and PVR [ 26 ]. Two independent investigations demonstrated that after initiation of PAH-specific therapy, only women show improvement in RV function despite similar improvement in PVR between the sexes [ 27 , 28 ]. Disparate RV recovery is thought to explain, at least in part, the poorer prognosis seen in men.…”