The role of age as a comorbidity in idiopathic and connective tissue disease-associated pulmonary arterial hypertension: from the Spanish Registry of Pulmonary Hypertension (REHAP Registry)

Abstract Introduction In the last decade, the number of patients diagnosed with pulmonary arterial hypertension (PAH) has increased, likely due to the ageing population and improved diagnostic precision in older patients. A thorough diagnostic approach has revealed that pulmonary hypertension is not solely attributable to left heart disease, resulting in a rise in the average age of PAH detection. However, the influence of age on comorbidity in these patients remains unclear. Purpose Evaluate the role of age in patients with idiopathic PAH (iPAH) and connective tissue disease-associated PAH (PAH-SSc) in the Spanish population. Methods Patients diagnosed with iPAH and PAH-SSc from 2014 to 2023 were collected from REHAP. Patients were classified into two groups based on an age cut-off of 60 years, a parameter included in the REVEAL 2.0 risk score and representing the median age of our cohort. We assessed the influence of age on baseline characteristics, exercise parameters, haemodynamic profiles, treatment initiation, and risk profiles in the first follow-up. Results 435 patients were included: 215 (49.5%) ≤ 60 years, and 220 (50.6%) 60 years. Patient characteristics are shown in Table. Older patients showed a shorter 6MWD, lower DLCO, and a less unfavourable haemodynamic profile, resulting in a better TAPSE/sPAP ratio. No significant differences were observed in functional class, sex, NT-proBNP, or pulmonary capillary wedge pressure. Most patients aged 60 years were in the PAH-SSc group (57.3%), while iPAH predominated in the ≤ 60 years group (60.9%) (p0.001). Comorbidities were more prevalent in the 60 years group, in which up to 31.4% had three or more comorbidities (p0.001). No differences were found in the initial ESC risk profile according to age group. In patients 60 years, oral monotherapy was the most common treatment (47.6%), while oral double therapy predominated in patients ≤ 60 years, with significantly higher use of prostacyclins (21.6% vs. 5.1%; p0.001). The survival analysis according to risk profile in first follow-up (low risk, intermediate-low risk, and intermediate-high or high risk) showed significant differences in patients ≤ 60 years (p0.001). However, in patients 60 years, no differences were observed between those at low risk and intermediate-low risk (p=0.005). Regarding the impact of comorbidities, no prognostic differences were found within each cohort based on the number of comorbidities. However, differences were observed according to age group, suggesting that age constitutes the most relevant prognostic factor (figure). Conclusions Age influences the clinical characteristics and treatment of patients with iPAH and PAH-SSc. In younger patients, follow-up risk profiles correlate with survival, unlike older patients, where no significant prognostic differences were found between low and intermediate-low risk. Age emerges as the most relevant prognostic factor, irrespective of the number of comorbidities.Table.Baseline Characteristics Figure.Kaplan-Meier Survival