Male survival disadvantage in pulmonary hypertension: independent of aetiology, age, disease severity, comorbidities and treatment

Background: Sex-based differences in morbidity and mortality in pulmonary hypertension (PH) are underexplored, yet understanding these differences is vital for improving clinical management. This study investigates the influence of sex on survival of patients with PH in dependency of various disease conditions. Methods: The PVRI GoDeep meta-registry integrates data from international PH registries, of which we analysed 21,123 incident hemodynamically fully characterised patients with PH. Survival analyses employed Kaplan–Meier and Cox proportional hazards models, adjusted for confounders and subjected to sensitivity analyses. Findings: Male patients consistently showed significantly higher mortality than females across the overall PH population (hazard ratio 1.36 [1.23, 1.50] after adjustment) and within PAH and non-PAH groups. These sex differences in survival persisted regardless of P(A)H severities, age and obesity, cardiovascular diseases, and PAH-specific therapies. The male survival disadvantage was noted across low-, intermediate-, and high-risk groups of the ESC/ERS 2022, REVEAL lite 2, and COMPERA 4-strata scores, but not the REVEAL 2.0 risk score, which incorporates male sex as non-modifiable factor. Stratification by race revealed that male sex was associated with worse survival in White patients, but not in Black or Asian patients with PH. Interpretation: Male patients with PH exhibit significantly higher mortality risks than females across both PAH and non-PAH PH groups. This disparity persists regardless of PH severity, underlying cause, age, obesity, comorbidities, or treatment status, though race might modify the observed risk difference. These insights provide new avenues for investigating underlying mechanisms and suggest including male sex as an independent factor in clinical risk assessment tools. Funding: This work is funded by thePulmonary Vascular Research Institute (PVRI) and theCardiovascular Medical Research and Education Fund (CMREF),NIH.