Age as an independent predictor of mortality in idiopathic and connective tissue disease-associated PAH: from the Spanish Registry of Pulmonary Hypertension (REHAP Registry)

Introduction

Pulmonary arterial hypertension (PAH) is increasingly diagnosed in older adults. Elderly patients frequently present with a higher burden of cardiovascular and metabolic comorbidities and are often treated less intensively. Although these factors are believed to contribute to poorer outcomes, it remains uncertain whether age itself independently determines prognosis.

Purpose

To assess the independent prognostic impact of age in a contemporary cohort of incident idiopathic PAH (IPAH) and connective tissue disease-associated PAH (CTD-PAH).

Methods

We conducted a retrospective cohort study using the Spanish national PAH registry (REHAP). Incident adults diagnosed between 2014 and 2023 were stratified by age (≤70 vs >70 years). Baseline clinical, haemodynamic and functional characteristics, treatment strategies, risk evolution according to ESC/ERS models, and survival were analysed. Survival was assessed using Kaplan–Meier analysis and Cox proportional hazards regression models including established prognostic variables and comorbidities.

Results

Among 435 patients (mean age 57±15 years; 21.1% >70 years), older patients more frequently had CTD-PAH (57.6% vs 39.1%), lower DLCO, worse exercise capacity (6MWD 296±108 vs 395±116 m), and a greater comorbidity burden (≥3 comorbidities: 34.8% vs 18.1%), despite exhibiting less severe haemodynamics. Baseline ESC/ERS risk distribution was comparable between age groups. Patient characteristics are shown in Table.

At first follow-up, patients >70 years were markedly less likely to achieve low-risk status (17.3% vs 50.0%) and more frequently remained on monotherapy (41.6% vs 20.1%), with lower rates of treatment escalation (Figure). Five-year survival was significantly reduced in patients >70 years, with survival curves separating after year 3 (log-rank P=0.007).

In univariate analysis, age >70 years was associated with increased mortality (HR 2.30; 95% CI 1.24–4.30; P=0.009). After multivariable adjustment for sex, PAH aetiology and individual comorbidities, age >70 years remained the only independent predictor of mortality (HR 2.21; 95% CI 1.04–4.69; P=0.039). When overall comorbidity burden was included in the model, ≥3 comorbidities independently predicted mortality (HR 3.00; 95% CI 1.12–8.20; P=0.029); however, this adverse prognostic impact was confined to patients >70 years and was not observed in younger individuals.

Conclusions

Age >70 years independently predicts worse survival in IPAH and CTD-PAH beyond established risk parameters and comorbidities. These findings support age-related vulnerability as a key determinant of outcomes in contemporary PAH.Baseline characteristicsFor image description, please refer to the figure legend and surrounding text.Risk and treatment evolution.For image description, please refer to the figure legend and surrounding text.