Abstract
Background2-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.MethodsThis 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.ResultsThe 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.ConclusionsHigh 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 registrationChiCTR-ROC-17011240. Registered 25 April 2017.
Highlights
Acute heart failure (AHF) is a life-threatening syndrome that needs prompt diagnosis and therapy (Mebazaa et al 2015; Cosentino and Campodonico 2018; Ahmad and Felker 2018)
We found that high 2OG level in serum showed a significant association with poor prognosis in chronic HF (CHF) patients (Chen et al 2014)
The advantage of hydrophilic interaction liquid chromatography (HILIC), which enable to enhance the retention of polar analytes and compatible with mass spectrometry (MS), makes the HILIC-LC/MS/MS a better approach to measure plasma 2OG compare to LC/MS/MS (Cubbon et al 2010)
Summary
Acute heart failure (AHF) is a life-threatening syndrome that needs prompt diagnosis and therapy (Mebazaa et al 2015; Cosentino and Campodonico 2018; Ahmad and Felker 2018). Circulating metabolic markers may play an important role in the risk stratification and prognosis assessment of HF, and in the guidance of treatment (Mebazaa et al 2015; Wang and Gupta 2015; Ibrahim and Januzzi Jr. 2018; Berezin 2018). We found that high 2OG level in serum showed a significant association with poor prognosis in CHF patients (Chen et al 2014). Advances in metabolite profiling technology have provided researchers with powerful tools with which to accurately measure 2OG levels (Dunn et al 2007; Magiera et al 2013). The advantage of hydrophilic interaction liquid chromatography (HILIC), which enable to enhance the retention of polar analytes (e.g., plasma 2OG) and compatible with mass spectrometry (MS), makes the HILIC-LC/MS/MS a better approach to measure plasma 2OG compare to LC/MS/MS (Cubbon et al 2010)
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