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Abstract：
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.
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.
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.
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.
ChiCTR-ROC-17011240 . Registered 25 April 2017.
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.
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.
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.
ChiCTR-ROC-17011240 . Registered 25 April 2017.
摘要：
2-酮戊二酸（2OG），三羧酸循环中的中间代谢物，已发现与慢性心力衰竭（HF）有关，但其对急性HF(AHF)患者短期不良结局的影响尚不确定.
这项前瞻性队列研究包括411名连续的AHF住院患者。住院期间,在入院的前24小时内收集空腹血浆样本.通过亲水作用液相色谱-液相色谱串联质谱(HILIC-LC/MS/MS)测量血浆20G水平。所有参与者均随访6个月。使用多元逻辑回归确定主要结局的比值比（OR）和95％置信区间（CI）。
AHF队列包括射血分数（EF）保留的HF（64.7％），中档EF（16.1%），并降低EF（19.2%），平均年龄为65（±13）岁，65.2%为男性。根据中位数2OG水平（μg/ml）将参与者分为两组：低组（<6.0，n=205）和高组（≥6.0，n=206）。在2OG和N末端B型利钠肽前体(NT-proBNP)水平之间存在相对适度的相关性(r=0.25;p<0.001)。在调整了年龄之后,性别,和身体质量指数,我们发现,NYHA分级的进展与血浆2OG水平的逐渐升高相关(趋势p<0.001).经过六个月的随访，发现76例（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%CI1.3-3.7,p=0.003),即使在校正NT-proBNP和估计肾小球滤过率(eGFR)后(OR:1.9,95%CI1.1-3.4,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％CI1.1-1.7，p=0.018）。
独立于NT-proBNP和eGFR的AHF患者高基线2OG水平与不良短期预后相关。因此，血浆2OG测量可能有助于AHF的风险分层和治疗监测。
ChiCTR-ROC-17011240。2017年4月25日注册
这项前瞻性队列研究包括411名连续的AHF住院患者。住院期间,在入院的前24小时内收集空腹血浆样本.通过亲水作用液相色谱-液相色谱串联质谱(HILIC-LC/MS/MS)测量血浆20G水平。所有参与者均随访6个月。使用多元逻辑回归确定主要结局的比值比（OR）和95％置信区间（CI）。
AHF队列包括射血分数（EF）保留的HF（64.7％），中档EF（16.1%），并降低EF（19.2%），平均年龄为65（±13）岁，65.2%为男性。根据中位数2OG水平（μg/ml）将参与者分为两组：低组（<6.0，n=205）和高组（≥6.0，n=206）。在2OG和N末端B型利钠肽前体(NT-proBNP)水平之间存在相对适度的相关性(r=0.25;p<0.001)。在调整了年龄之后,性别,和身体质量指数,我们发现,NYHA分级的进展与血浆2OG水平的逐渐升高相关(趋势p<0.001).经过六个月的随访，发现76例（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%CI1.3-3.7,p=0.003),即使在校正NT-proBNP和估计肾小球滤过率(eGFR)后(OR:1.9,95%CI1.1-3.4,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％CI1.1-1.7，p=0.018）。
独立于NT-proBNP和eGFR的AHF患者高基线2OG水平与不良短期预后相关。因此，血浆2OG测量可能有助于AHF的风险分层和治疗监测。
ChiCTR-ROC-17011240。2017年4月25日注册
