Increased serum 2-oxoglutarate associated with high myocardial energy expenditure and poor prognosis in chronic heart failure patients

Abstract

Myocardial energy expenditure (MEE) and 2-oxoglutarate are elevated in chronic heart failure (CHF) patients compared with healthy controls. To explore whether 2-oxoglutarate could reflect the levels of MEE and predict the prognosis of CHF, 219 CHF patients and 66 healthy controls were enrolled. 2-Oxoglutarate was assayed with Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC/MS/MS). CHF patients were divided into 4 groups according to interquartile range of MEE and followed for death or recurrent hospital admission due to CHF for the mean follow-up time 6.64±0.16months. 2-Oxoglutarate was increased in CHF patients compared with controls (P<0.01) and correlated with estimated glomerular filtration rate (r=0.142, P=0.036), age (r=-0.269, P<0.01) and MEE levels (r=0.307, P<0.01) in a multiple linear correlation analysis in CHF patients. Furthermore, 2-oxoglutarate (OR=3.470, 95% CI=1.557 to 7.730, P=0.002), N-terminal pro-B-type natriuretic peptide (OR=4.013, 95% CI=1.553 to 10.365, P=0.004), age (OR=1.611, 95% CI=1.136 to 2.283, P=0.007) and left ventricular ejection fraction (OR=7.272, 95% CI=3.110 to 17.000, P<0.001) were independently associated with MEE on multiple logistic regression analysis. Kaplan-Meier event curves showed that high 2-oxoglutarate levels were associated with adverse outcomes (Log Rank, Chi(2)=4.026, P=0.045). This study showed that serum 2-oxoglutarate is associated with MEE levels, which can be used as potential biomarkers for MEE, and it can reflect the clinical severity and short-term outcome of CHF.

The metabolic fingerprints of HCV and HBV infections studied by Nuclear Magnetic Resonance Spectroscopy

“…In fact, both metabolites were found to be altered in association to cardiovascular diseases and were therefore previously identified as potential biomarkers of cardiovascular risk. In more detail, high levels of 2-oxoglutarate were present in patients with heart failure 39,40 , with chronic resistant hypertension 41 and could more generally be considered as biomarkers of cardiovascular risk 42 . In addition, high levels of the ketone-body 3-hydroxybutyrate were also found to be associated with cardiovascular diseases 43,44 and were identified as part of a panel of cardiovascular risk biomarkers through different analyses 45,46 .…”

Effect of Diabetes on the Assessment Role of 2-Oxoglutarate to the Severity of Chronic Heart Failure

“…It has been reported that some metabolites may associate with the state of cardiac energy metabolism and severity of CHF [9,10]. Our previous study also showed that serum 2-oxoglutarate was associated with myocardial energy expenditure and can reflect the short-term outcome of CHF [11]. However, until recently, little was known about the relationship between the serum 2-oxoglutarate level and severity of CHF in T2DM.…”

“…Among these, 2-oxoglutarate, a major intermediate metabolite of the tricarboxylic acid cycle, plays important roles in regulating myocardial energy metabolism. Recently, our study showed that 2-oxoglutarate was associated with myocardial energy expenditure and can reflect the clinical severity and short-term outcome of heart failure in CHF patients without type 2 diabetes mellitus (T2DM) [11]. However, it is not clear whether these predictive roles still exist in CHF patients with T2DM.…”

Association between admission plasma 2-oxoglutarate levels and short-term outcomes in patients with acute heart failure: a prospective cohort study

“…Intermediate metabolites contribute to generate adenosine triphosphate (ATP) for energy and control cell growth and regeneration by providing precursor and signaling molecules (Doenst et al 2013). Research suggests that the presence of intermediate metabolites may reveal disease status, predict disease progression, and provide valuable prognostic information (Wang et al 2017; Liu et al 2018; Dunn et al 2007; Maus and Peters 2017; Chen et al 2014). In previous study, we found that high 2OG level in serum showed a significant association with poor prognosis in CHF patients (Chen et al 2014).…”