Can Plasma ADAMTS13 Differentiate Patients With Pulmonary Arterial Hypertension From Other Forms of Pulmonary Hypertension and Dyspnea Control Patients

Background: Multimarker panels of blood-borne biomarkers could aid in shortening the diagnostic delay of pulmonary arterial hypertension (PAH). Research Question: Can any of the 61 proteins included in the study, related to pathways known to be involved in PAH pathophysiology (eg, coagulation, inflammation, fibrosis), differentiate PAH from other forms of pulmonary hypertension (PH) and/or dyspnea and thus aid in diagnosing PAH? Study Design and Methods: Plasma samples were collected from 55 healthy control participants and 355 patients at diagnosis, including PAH (n = 95), chronic thromboembolic PH (n = 54), heart failure with preserved ejection fraction with PH (n = 58), heart failure with reduced ejection fraction with PH (n = 64), a non-PH dyspnea control group with heart failure (n = 45), and an independent external PAH cohort (n = 39) used as external validation of protein levels in the PAH group of the discovery cohort. Plasma levels of the 61 proteins were analyzed using proximity extension assay. Results: ADAMTS13 plasma levels differed in patients with PAH compared with the 3 other PH groups and the non-PH dyspnea group (P < .05). In univariable (OR, 0.90; 95% CI, 0.84-0.96) and multivariable logistic regression models adjusted for age and sex (OR, 0.89; 95% CI, 0.83-0.96), ADAMTS13 was additionally able to differentiate PAH from the other combined disease groups. In the external validation cohort, plasma ADAMTS13 levels in PAH were statistically equivalent to the discovery cohort (P < .002). Interpretation: Plasma ADAMTS13 may be a diagnostic biomarker in PAH with the ability to differentiate patients with PAH from other dyspnea groups and is an interesting protein for inclusion in future studies of multimarker panels. Further validation in larger cohorts is warranted.