Idiopathic pulmonary arterial hypertension, associated with connective tissue disease and comorbidities: prognostic differences? Results the Spanish Registry of pulmonary hypertension (REHAP Registry)
Authors: Bravo-Marques R , Rivas-Ruiz F , Escribano-Subias P , Tenes J A , Becerra-Munoz V M , Soto-Abanades C I , Cruz-Utrilla A , Lopez-Meseguer M , Martinez-Menaca A , Alvarez-Barredo M , Lacuey Lecumberri G , Sintes H , Torrents A , Del Pozo R , Blanco I 
Published: October 2024

Abstract

Introduction
Idiopathic pulmonary arterial hypertension (iPAH) and associated with connective tissue disease (PAH-SSc) are the most frequent groups of pulmonary arterial hypertension (PAH) but their long-term survival is usually unequal. Comorbidities, increasing in frequency in these patients, show prognostic influences but it is not known whether these differ in both groups of patients.

Methods
We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classifies into iPAH and PAH-SSc.
We analyzed baseline characteristics and the distribution of the different comorbidities in the two groups.
Survival analyses estimated by Kaplan-Meier analysis using the log-rank test were done according to PAH etiology and comorbidities and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival.

Results
Seven hundred and fifty-seven patients were selected for this study.
The characteristics of the patients are shown in Table 1.
Patients with PAH-SSc compared to iPAH were older (62 vs 56 years), more female (81.8% vs 62.4%), had a more favorable hemodynamic profile, TAPSE/sPAP ratio and lower NT-proBNP levels. No differences were found in functional class or 6MWT.
We found a higher proportion of patients in a low and intermediate risk profile, according to ESC, in patients with PAH-SSC as opposed to PAHi (46.8/50.9% vs. 29.3/64.5%; p&lt;0.001).
Regarding comorbidities, history of smoking (27.1 vs 54%; p&lt;0-001), obesity (17.1 vs 20.7%; p&lt;0.001) and diabetes (9.4 vs 22.1%; p&lt;0.001) are less frequent in PAH-SSc than in iPAH. There are no differences in the rest of the comorbidities studied in the two groups of patients.
In a survival analysis, we found no differences between patients with iPAH and PAH-SSc at 7-year follow-up.
Patients with ≥ 3 comorbidities had statistically significantly higher mortality (p&lt;0.001) compared to those with 0 or 1-2 comorbidities in both etiologies. There were no differences between 0 and 1-2 comorbidities. (Figure 1).
Variables associated with mortality were male sex (HR 1.9, 95% CI 1,28 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06), the intermediate risk profile (HR 2.64, 95% CI 1.62 – 4.32) and high risk profile (HR 9.97, 95% CI 4.36 – 18.47), but not etiology. The presence of connective tissue diseases, were not associated with increased mortality.

Conclusions
Patients with PAH-SSc show lower comorbidities, better hemodynamic profile, RV-PA coupling and risk profile than those with iPAH.
Comorbidity has a great relevance in survival but without differences according to etiology.
The presence of male sex, age, the intermediate and high risk profile is associated with worse survival, but not the connective tissue diseases.