期刊
METABOLITES
卷 11, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/metabo11040196
关键词
acylcarnitines; fatty acids; heart failure; type 2 pulmonary hypertension
资金
- Montreal Heart Institute Foundation
- Fonds de Recherche en Sante du Quebec (FRQS) [277167, 281577]
- Foundation Marcelle et Jean Coutu, Cal & Janine Moisan Chair
- Genome Quebec [PRF-2017-23]
- Institute for Data Valorization (IVADO)
- FRSQ [278281]
- FRSQ/FNRS [281275]
- Canada Research Chair (Senior)
- Universite de Montreal Pfizer-endowed research chair
Defects in fatty acid utilization have been well described in group 1 pulmonary hypertension and heart failure, yet poorly studied in group 2 PH. This study compared the circulating metabolomic profile of patients with HF with and without PH, showing that FA-related metabolites were differently affected in HF with or without PH, which may convey adverse outcomes. The study suggests a potential correlation between certain metabolites and NT-proBNP levels in patients with HF and PH.
Defects in fatty acid (FA) utilization have been well described in group 1 pulmonary hypertension (PH) and in heart failure (HF), yet poorly studied in group 2 PH. This study was to assess whether the metabolomic profile of patients with pulmonary hypertension (PH) due HF, classified as group 2 PH, differs from those without PH. We conducted a proof-of-principle cross-sectional analysis of 60 patients with chronic HF with reduced ejection fraction and 72 healthy controls in which the circulating level of 71 energy-related metabolites was measured using various methods. Echocardiography was used to classify HF patients as noPH-HF (n = 27; mean pulmonary artery pressure [mPAP] 21 mmHg) and PH-HF (n = 33; mPAP 35 mmHg). The profile of circulating metabolites among groups was compared using principal component analysis (PCA), analysis of covariance (ANCOVA), and Pearson's correlation tests. Patients with noPH-HF and PH-HF were aged 64 +/- 11 and 68 +/- 10 years, respectively, with baseline left ventricular ejection fractions of 27 +/- 7% and 26 +/- 7%. Principal component analysis segregated groups, more markedly for PH-HF, with long-chain acylcarnitines, acetylcarnitine, and monounsaturated FA carrying the highest loading scores. After adjustment for age, sex, kidney function, insulin resistance, and N-terminal pro-brain natriuretic peptide (NT-proBNP), 5/15 and 8/15 lipid-related metabolite levels were significantly different from controls in noPH-HF and PH-HF subjects, respectively. All metabolites for which circulating levels interacted between group and NT-proBNP significantly correlated with NT-proBNP in HF-PH, but none with HF-noPH. FA-related metabolites were differently affected in HF with or without PH, and may convey adverse outcomes given their distinct correlation with NT-proBNP in the setting of PH.
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