Lipidomics for diagnosis and prognosis of pulmonary hypertension (Q6715959)

Pulmonary hypertension (PH) is associated with high morbidity and mortality with an urgent need for diagnostic and prognostic biomarkers. A training cohort of PH patients, disease controls without PH, and healthy controls was investigated using metabolomics and machine learning. Specific free fatty acid (FFA)/lipid-ratio biomarkers were diagnostic and predictive for PH survival with an area under the curve (AUC) of 0.89. FFA/lipid-ratio performance was independently validated in PH patients from other centers(AUC 0.90). Survival could be predicted in an age-independent manner and a combination with established clinical scores (FPHR4p, COMPERA 2.0) increased the scores hazard risk. Our mechanistic studies in healthy and diseased pulmonary artery endothelial and smooth muscle cells indicate a functional involvement of increased FFA levels in pathophysiology of PH. In conclusion, lipidomic changes in PH can be used as a novel diagnostic and prognostic approach and may help the discovery of new therapeutic targets.