Impact of cardiovascular comorbidity burden in pulmonary arterial hypertension: a propensity score-matched analysis
Q Wang, Q Luo, Z LiuAbstract
Background
Pulmonary arterial hypertension (PAH) with cardiovascular comorbidities represents a distinct phenotype characterized by left heart disease-related risk factors despite precapillary hemodynamics. A quantitative tool to capture the cardiovascular burden and its prognostic impact in PAH is lacking.
Purpose
To determine the impact of cardiovascular comorbidity burden on early outcomes in PAH and to evaluate whether the quantitative tool to reflect comorbidity burden adds prognostic value beyond conventional risk stratification.
Methods
We retrospectively enrolled 331 patients with PAH confirmed by right heart catheterization and stratified them by the number of cardiovascular comorbidities (hypertension, diabetes, atrial fibrillation, coronary artery disease, obesity): 0 (n=120), 1 (n=144), and ≥2 (n=67). Baseline clinical characteristics and hemodynamics were collected. H2FPEF score was calculated as a quantitative surrogate of cardiovascular burden. Propensity score matching based on age and sex generated a balanced cohort of 188 patients for independent prognostic validation. Matched Cox regression assessed associations of comorbidity burden and H2FPEF with 1-year clinical worsening. Incremental prognostic value of H2FPEF beyond the 2022 ESC/ERS 3-strata tool and REVEAL 2.0 was evaluated using Harrell’s C-index, with Kaplan–Meier analyses performed within intermediate-risk group identified by the traditional risk calculators.
Results
Increasing comorbidity burden was associated with older age (36.1±12.1 vs 49.6±15.0 vs 59.2±14.7; P<0.001), lower 6-minute walk distance (412.9±109.6 vs 379.3±103.6 vs 340.6±116.9m; P=0.001), higher NT-proBNP (P=0.014), higher pulmonary arterial wedge pressure (P=0.021), and a higher prevalence of H2FPEF>6 (0% vs 4.9% vs 32.8%; P<0.001), while mean pulmonary arterial pressure showed a decreasing trend (P<0.001). The 1-year clinical worsening occurred in 5.0%, 20.1%, and 14.9% of patients, respectively (P=0.002). In the matched cohort, cardiovascular comorbidity burden was associated with higher risk of 1-year clinical worsening (aHR=3.37, 95% CI 1.2–9.1; P=0.017). H2FPEF ≥2 independently predicted 1-year clinical worsening (aHR=4.13; P<0.05). Discrimination of REVEAL 2.0 and ESC/ERS was poor in patients with comorbidities (C-index 0.582 and 0.520), but improved with integration of H2FPEF (0.696 and 0.668, P<0.01). H2FPEF≥2 further identified a higher risk within patients with intermediate risk patients (P<0.001).
Conclusions
Cardiovascular comorbidity burden is associated with increased risk of 1-year clinical worsening in PAH. H2FPEF provides a practical quantitative measure of the burden and improves risk prediction beyond conventional tools, supporting its use for more precise risk assessment in PAH patients with more cardiovascular comorbidities.H2FPEF in risk assessmentFor image description, please refer to the figure legend and surrounding text.flow chartFor image description, please refer to the figure legend and surrounding text.