Abstract 16622: Plasma Metabolomic Profiles Differentiate Hemodynamic Subtypes of Pulmonary Hypertension
Introduction: Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressures (mPAP) ≥ 25 mmHg. Within PH, there are distinct hemodynamic subgroups based on the presence of hypertension in the precapillary or postcapillary beds of the pulmonary vasculature: pulmonary arterial hypertension (PAH - precapillary PH), passive PH secondary to left heart disease (postcapillary PH) and mixed PH with both precapillary and postcapillary components.
Hypothesis: As metabolic abnormalities have been noted in PAH and heart failure, we hypothesized that different hemodynamic subtypes of PH would be associated with distinct plasma metabolomic profiles.
Methods: The CATHGEN biorepository consists of biological samples collected on over 9000 individuals undergoing cardiac catheterization at Duke University Medical Center. Of those subjects who had targeted metabolomics studies performed, 282 were identified with mPAP ≥ 25 mmHg. Of these 282 subjects, 133 met criteria for passive PH (PCWP > 15 mmHg, PVR 15 mmHg, PVR ≥ 3 WU) and 67 for PAH (PCWP ≤ 15 mmHg). Tandem flow injection mass spectrometry (MS) with isotope-labeled internal standards were used for targeted quantitative measurements of ~ 60 metabolites (including free fatty acids, acylcarnitines, amino acids, lipids and ketones). Multivariable logistic regression adjusted for age, presence of coronary artery disease, sex, race, diabetes and ejection fraction were used to determine differences in metabolites between the pulmonary HTN subgroups and with a matched cohort of CATHGEN subjects free from PH (N=280, matched on 282).
Results: All PH subgroups demonstrated significantly different levels of long chain acylcarnitines from controls (p < 0.01). Compared to controls, subjects with mixed PH also had significant differences in long chain dicarboxyl acylcarnitines (p < 0.01) and C3-C5s (p < 0.028), passive PH had significant differences in ketone related metabolites (p < 0.04), and PAH had significant differences in branched chain amino acids (p < 0.01).
Conclusions: Passive, mixed and PAH subtypes of PH were associated with distinct plasma metabolomics profiles compared to matched controls. These finding demonstrate that specific metabolic changess develop in the distinct subtypes of PH.
Author Disclosures: N. Luo: None. D.M. Craig: None. O. Ilkayeva: None. J. Bain: None. M. Muehlbauer: None. W.E. Kraus: Other; Significant; Patent on an unrelated metabolomics finding. C.B. Newgard: Other; Significant; Patent on an unrelated metabolomics finding. S.H. Shah: Other; Significant; Patent on an unrelated metabolomics finding. S. Rajagopal: Research Grant; Significant; Gilead Sciences, NIH, Burroughs Wellcome Fund. Consultant/Advisory Board; Significant; Gilead Sciences, Bayer.
- © 2015 by American Heart Association, Inc.