Baseline high-density lipoprotein cholesterol and heterogeneous long-term outcomes in pulmonary arterial hypertension

High-density lipoprotein cholesterol (HDL-C) has been evaluated in relation to outcome, but survival findings among patients with pulmonary arterial hypertension (PAH) have varied across cohorts. We therefore tested whether the HDL-C–mortality relationship differed by baseline disease severity. The study included 231 adults with newly diagnosed PAH who had received no PAH-specific treatment before right heart catheterization. Baseline COMPERA 2.0 risk was calculated from WHO functional class (WHO-FC), 6-minute walk distance (6MWD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). HDL-C entered the Cox model as a continuous variable, with estimates expressed per 10 mg/dL increase. Restricted cubic splines were fitted across the observed HDL-C range, and HDL-C-by-risk interaction terms were tested across COMPERA 2.0 strata. Follow-up lasted a median of 60.2 months; 64 deaths were recorded (27.7%). With age, sex, PAH subtype, and log₁₀ NT-proBNP included in the model, the HR for death was 0.34 per 10 mg/dL higher HDL-C (95% CI 0.22–0.54; P < 0.001). Similar associations were observed in sensitivity analyses incorporating WHO-FC, 6MWD, cardiac index, uric acid, or the continuous COMPERA 2.0 score. The association was non-linear (P for non-linearity = 0.001). A significant interaction was observed between HDL-C and COMPERA 2.0 risk stratum ( P = 0.0003). Inverse associations were evident in the intermediate-high-risk (HR 0.20, 95% CI 0.10–0.41) and high-risk (HR 0.24, 95% CI 0.07–0.84) strata, but not in the intermediate-low-risk stratum (HR 1.87, 95% CI 0.91–3.84). Excluding congenital heart disease-associated PAH did not materially change the overall association. Baseline risk was an important source of variation in the HDL-C findings. Inverse associations were clear in the intermediate-high- and high-risk groups, whereas the estimate in the intermediate-low-risk group was less precise.