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Mol Med. 2019 Mar 28;25(1):8. doi: 10.1186/s10020-019-0078-1.

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

Peng Z1,2, Zhan Q1,2, Xie X1,2, Li H1,2, Tu Y1,2, Bai Y1,2, Huang X1,2, Lai W1,2, Zhao B3, Zeng Q1,2, Xu D4,5.

Author information

1
State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, China.
2
Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of China, Guangzhou, China.
3
Department of Pharmacy,Nanfang Hospital, Rational Medication Evaluation and Drug Delivery Technology Lab, Guangdong Key Laboratory of New Drug Screening, Guangzhou, China.
4
State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, China. dinglixu@fimmu.com.
5
Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of China, Guangzhou, China. dinglixu@fimmu.com.

Abstract

BACKGROUND:

2-oxoglutarate (2OG), an intermediate metabolite in the tricarboxylic acid cycle, has been found to associate with chronic heart failure (HF), but its effect on short-term adverse outcomes in patients with acute HF (AHF) is uncertain.

METHODS:

This prospective cohort study included 411 consecutive hospitalized patients with AHF. During hospitalization, fasting plasma samples were collected within the first 24 h of admission. Plasma 2OG levels were measured by hydrophilic interaction liquid chromatography-liquid chromatography tandem mass spectrometry (HILIC-LC/MS/MS). All participants were followed up for six months. Multiple logistic regression was used to determine the odds ratio (OR) and 95% confidence interval (CI) for primary outcomes.

RESULTS:

The AHF cohort consisted of HF with preserved ejection fraction (EF) (64.7%), mid-range EF (16.1%), and reduced EF (19.2%), the mean age was 65 (±13) years, and 65.2% were male. Participants were divided into two groups based on median 2OG levels (μg/ml): low group (< 6.0, n = 205) and high group (≥6.0, n = 206). There was a relatively modest correlation between 2OG and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels (r = 0.25; p < 0.001). After adjusting for age, sex, and body mass index, we found that the progression of the NYHA classification was associated with a gradual increase in plasma 2OG levels (p for trend< 0.001). After six months of follow-up, 76 (18.5%) events were identified. A high baseline 2OG level was positively associated with a short-term rehospitalization and all-cause mortality (OR: 2.2, 95% CI 1.3-3.7, p = 0.003), even after adjusting for NT-proBNP and estimated glomerular filtration rate (eGFR) (OR: 1.9, 95% CI 1.1-3.4, p = 0.032). After a similar multivariable adjustment, the OR was 1.4 (95% CI 1.1-1.7, p = 0.018) for a per-SD increase in 2OG level.

CONCLUSIONS:

High baseline 2OG levels are associated with adverse short-term outcomes in patients with AHF independent of NT-proBNP and eGFR. Hence plasma 2OG measurements may be helpful for risk stratification and treatment monitoring in AHF.

TRIAL REGISTRATION:

ChiCTR-ROC-17011240 . Registered 25 April 2017.

KEYWORDS:

2-oxoglutarate; Acute heart failure; Cohort; Prognosis

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