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.

中文翻译：

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急性心力衰竭患者入院血浆 2-氧戊二酸水平与短期结果之间的关联：一项前瞻性队列研究

背景 2-酮戊二酸 (2OG) 是三羧酸循环中的一种中间代谢物，已被发现与慢性心力衰竭 (HF) 相关，但其对急性 HF (AHF) 患者短期不良结局的影响尚不确定。前瞻性队列研究包括 411 名连续住院的 AHF 患者。在住院期间，在入院后的前 24 小时内收集空腹血浆样本。通过亲水相互作用液相色谱-液相色谱串联质谱 (HILIC-LC/MS/MS) 测量血浆 2OG 水平。所有参与者都被随访了六个月。使用多元逻辑回归来确定主要结果的优势比 (OR) 和 95% 置信区间 (CI)。结果 AHF 队列包括射血分数 (EF) 保留的 HF (64.7%)、中程 EF (16. 1%)，EF 降低 (19.2%)，平均年龄为 65 (±13) 岁，65.2% 为男性。参与者根据中位 2OG 水平 (μg/ml) 分为两组：低组 (< 6.0，n = 205) 和高组 (≥6.0，n = 206)。2OG 与 N 端 B 型利钠肽原 (NT-proBNP) 水平之间存在相对适度的相关性（r = 0.25；p < 0.001）。在调整年龄、性别和体重指数后，我们发现 NYHA 分类的进展与血浆 2OG 水平的逐渐增加有关（趋势 p < 0.001）。六个月的随访后，确定了 76 个（18.5%）事件。高基线 2OG 水平与短期再住院和全因死亡率呈正相关（OR：2.2，95% CI 1.3-3.7，p = 0.003），即使在调整 NT-proBNP 和估计的肾小球滤过率 (eGFR) 之后（OR：1.9，95% CI 1.1–3.4，p = 0.032）。经过类似的多变量调整后，2OG 水平每 SD 增加的 OR 为 1.4（95% CI 1.1-1.7，p = 0.018）。结论 高基线 2OG 水平与 AHF 患者的不良短期结果相关，独立于NT-proBNP 和 eGFR。因此，血浆 2OG 测量可能有助于 AHF 的风险分层和治疗监测。试验注册 ChiCTR-ROC-17011240。2017 年 4 月 25 日注册。因此，血浆 2OG 测量可能有助于 AHF 的风险分层和治疗监测。试验注册 ChiCTR-ROC-17011240。2017 年 4 月 25 日注册。因此，血浆 2OG 测量可能有助于 AHF 的风险分层和治疗监测。试验注册 ChiCTR-ROC-17011240。2017 年 4 月 25 日注册。