Plasma adrenomedullin peptides and precursor levels in pulmonary arterial hypertension disease severity and risk stratification.

Adrenomedullin is a potent vasodilatory peptide, linked to pulmonary arterial hypertension pathology. Proximity extension assays were utilized to study plasma biomarkers related to vasoregulation, with focus on adrenomedullin peptides and precursor levels, collectively referred to as ADM. ADM was measured in 48 treatment-naïve pulmonary arterial hypertension patients at diagnosis, and in 31 of them at an early treatment follow-up. Plasma ADM was additionally assessed in patients with chronic thromboembolic pulmonary hypertension (n = 20) and pulmonary hypertension due to heart failure with preserved (HFpEF(PH)) (n = 33) or reduced (HFrEF(PH)) (n = 36) ejection fraction, as well as healthy controls (n = 16). ADM was studied in relation to pulmonary arterial hypertension hemodynamics, risk assessment, prognosis, treatment response, and differentiation. Plasma ADM levels in pulmonary arterial hypertension patients at diagnosis were higher than in healthy controls (p < 0.001), similar as in chronic thromboembolic pulmonary hypertension patients (p = ns), but lower compared to HFpEF(PH) (p < 0.03) and HFrEF(PH) (p < 0.001). In pulmonary arterial hypertension, specifically, plasma ADM at diagnosis correlated mainly to mean right atrial pressure (r = 0.73, p < 0.001), N-terminal prohormone of brain natriuretic peptide (r = 0.75, p < 0.001), six-minute walking distance (r = -0.57, p < 0.001), and venous oxygen saturation (r = -0.57, p < 0.001). ADM also correlated to the ECS/ERS- (r = 0.74, p < 0.001) and REVEAL risk scores (r = 0.54, p < 0.001) at pulmonary arterial hypertension diagnosis. Plasma ADM in pulmonary arterial hypertension patients was unaltered at early treatment follow-up compared to baseline (p = ns). Pulmonary arterial hypertension patients with supra-median ADM at diagnosis showed worse overall survival than those with infra-median levels (median survival 34 versus 66 months, p = 0.0077). In conclusion, the present results suggest that baseline plasma ADM levels mirror disease severity, correlating to both ECS/ERS- and the REVEAL risk scores.