Metabolomics of Right Ventricular Function in Pulmonary Hypertension.
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Chacon-Barahona Jonathan, Chung Samuel J, Garry Jonah D, Frantz Robert P, Rischard Franz, Hassoun Paul M, Mathai Stephen C, Simpson Catherine E, Beck Gerald, Hill Nicholas S, Leopold Jane A, Waxman Aaron B, Rosenzweig Erika B, Borlaug Barry A, Mukherjee Monica, Vanderpool Rebecca R, Jacob Miriam, Mehra Reena, Park Margaret M, Finet J Emanuel, Farha Samar, Grunig Gabriele, Kwan Deborah H, Comhair Suzy, Erzurum Serpil, Barnard John, Hu Bo, Jellis Christine L, Racanelli Alexandra C, Krumsiek Jan, Brittain Evan L, Hemnes Anna R, Horn Evelyn M, PVDOMICS Study Group
Аннотация
METHODS: We analyzed data from the multicenter PVDOMICS (Pulmonary Vascular Disease Phenomics) cohort. RV systolic function metrics included fractional area change (echo), global longitudinal strain (echo), and ejection fraction (cardiac magnetic resonance). We used linear regression adjusted for age, sex, body mass index, and PH group to assess associations between metabolites and RV function. Pathway enrichment analyses were used to identify pathways significantly associated with RV function. Interaction terms were assessed to determine whether metabolite associations were modified by pulmonary vascular resistance, group 1 PH status, or sex. Least absolute shrinkage and selection operator regression was used to develop metabolite-based scores for RV function, and prognostic performance was assessed.
RESULTS: There were 979 participants with plasma metabolomics and RV function data. Linear regression identified 170 metabolites that were significantly associated with all 3 RV metrics. Androgenic steroid, gamma-glutamyl amino acid, polyamine, vitamin A, fatty acid, and sterol pathways are most strongly associated with RV systolic function. Two metabolites interacted with group 1 PH status, and 6 interacted with pulmonary vascular resistance. Four androgenic steroids are associated more strongly with RV systolic function in women compared with men. Metabolite-based scores were prognostically equivalent to RV systolic function metrics and less accurate than REVEAL Lite 2 scores.
CONCLUSIONS: We provide a blueprint of metabolites and metabolic pathways associated with RV systolic function across the spectrum of PH. Novel links to vitamin A and glutathione metabolites were observed. We detected few metabolites that associated with RV systolic function differentially by group 1 PH status or degree of pulmonary vascular resistance elevation. Androgenic steroids may associate more strongly with RV systolic function in women compared with men.