Sex differences in pulmonary arterial hypertension: Insights from the FOCUS-PAH registry

Background: Despite the higher incidence of pulmonary arterial hypertension (PAH) in women, sex differences in terms of clinical presentation and prognosis are still uncertain. We assess the impact of sex in patients with PAH. Methods: Sex differences were evaluated in the multicenter FOCUS-PAH registry, that included patients diagnosed with PAH at 7 tertiary care centers between 2001 and 2022. Patients' characteristics and outcomes were compared in men vs. women, and factors independently associated with long-term outcomes were assessed. The primary endpoint was overall survival. Results: Among 410 included patients, 273 (66.6 %) were women and 137 (33.4 %) were men. Despite similar age, men had more cardio-renal-metabolic comorbidities and history of HIV infection, whereas women had more connective tissue disorders and scleroderma, and worse functional capacity. Dual therapy was more commonly prescribed in women (39.9 % vs. 27.0 %). At multivariable Cox regression analysis, female sex was independently associated with a lower risk of all-cause mortality (adjusted hazard ratio 0.60, 95 % confidence interval 0.38-0.95, p = 0.031). Age, European Society of Cardiology (ESC) / European Respiratory Society (ERS) risk score, glomerular filtration rate and scleroderma were independently associated with long-term mortality in women, whereas only age and ESC/ERS risk score independently predicted this endpoint in men. Conclusions: In this real-world registry, women represented 2 out of 3 patients with PAH and female sex was independently associated with a lower risk of mortality. There were differences in the variables associated with long-term mortality between sexes, suggesting that individualized approach to risk stratification should also include sex.