New phenotype and outcomes in connective tissue disease-associated pulmonary arterial hypertension: relevance of age-related comorbidities

OBJECTIVES: To assess the demographic and clinical characteristics (including the burden of comorbidities) and the survival rates of patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and to compare them with those of contemporary patients with idiopathic PAH (IPAH). We also evaluated the impact of emerging age-related comorbidities on survival. METHODS: This was a retrospective cohort study based on data from patients included in the Spanish Registry of PAH (REHAP) during 2014-2023. Kaplan-Meier survival estimates were calculated (overall and according to ≥3 vs 1-2 or no comorbidities). Prognostic values were analysed using Cox proportional-hazards regression models. RESULTS: A total of 340 CTD-PAH patients and 417 IPAH patients were included in the analysis (n = 757). CTD-PAH patients were older than IPAH patients [62 (14) vs 56 (17) years old] and showed lower comorbidity burden (17% vs 34% patients with ≥3 comorbidities), both P < 0.001. The 1-, 3- and 5-year survival rates were 97%, 76% and 55%, respectively, for CTD-PAH and 93%, 77% and 54%, respectively, for IPAH (P = 0.884). Of the seven comorbidities analysed, only chronic kidney disease (CKD) was associated with poor prognosis after adjustment for known PAH prognostic factors (hazard ratio 1.83; 95% CI: 1.19, 2.80), independently of aetiology. CTD-PAH received monotherapy more frequently (37% vs 52% in IPAH). CONCLUSION: Contemporary CTD-PAH patients included in REHAP are older and have a lower comorbidity burden than IPAH patients, while exhibiting similar survival rates up to 5 years. CKD is an independent prognostic factor in both aetiologies. CTD-PAH patients tend to receive a more conservative treatment approach.