Plasma amino acid profiling improves predictive accuracy of adverse events in patients with heart failure.
Plasma amino acid profiling improves predictive accuracy of adverse events in patients with heart failure.
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DOI：
10.1002/ehf2.13572
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发表时间：
2021-12
影响因子：
3.8
通讯作者：
Miura T
中科院分区：
文献类型：
--
作者：
Kouzu H;Katano S;Yano T;Ohori K;Nagaoka R;Inoue T;Takamura Y;Ishigo T;Watanabe A;Koyama M;Nagano N;Fujito T;Nishikawa R;Ohwada W;Miura T
心力衰竭（HF）的临床结局因多种合并症（包括营养不良和恶病质）的存在而变得复杂，并且对每位患者的结局预测仍然困难。包括氨基酸谱分析在内的代谢组学能够检测全身代谢的变化。本研究的目的是确定血浆氨基酸谱分析是否能改善对心力衰竭患者临床结局的预测。
我们回顾性研究了301例心力衰竭患者（年龄70±15岁；59%为男性）。在心力衰竭稳定后，于空腹状态采集用于测量氨基酸浓度的血液样本。使用超高效液相色谱法测量血浆氨基酸浓度。本研究的临床终点是不良事件，定义为全因死亡以及因心力衰竭恶化或致死性心律失常导致的非计划性再入院。在平均随访380±214天期间，40例患者（13%）发生了不良事件。投影得分中变量重要性分析的结果（一种在偏最小二乘法 - 判别分析（PLS - DA）中衡量变量重要性的指标）显示，与不良事件相关的前五种氨基酸是3 - 甲基组氨酸（3 - Me - His）、β - 丙氨酸、缬氨酸、羟脯氨酸和色氨酸。多变量Cox比例风险分析表明，3 - Me - His浓度高以及β - 丙氨酸和缬氨酸浓度低与不良事件独立相关。当根据由受试者工作特征曲线计算出的氨基酸截断值对心力衰竭患者进行分组时，Kaplan - Meier生存曲线显示，3 - Me - His高的心力衰竭患者无事件生存率低于3 - Me - His低的心力衰竭患者（68%对91%，P < 0.01）。在3 - Me - His高的亚组中，β - 丙氨酸低的心力衰竭患者和缬氨酸低的心力衰竭患者无事件生存率分别显著低于β - 丙氨酸高的心力衰竭患者和缬氨酸高的心力衰竭患者。另一方面，在3 - Me - His低的患者亚组中，β - 丙氨酸低和缬氨酸低的心力衰竭患者与无此情况的心力衰竭患者之间的无事件生存率Kaplan - Meier曲线无差异。将3 - Me - His高以及β - 丙氨酸低或缬氨酸低纳入包含N - 末端脑利钠肽前体的调整模型中，提高了出院后不良事件预测的准确性。3 - Me - His浓度与肌肉质量和营养状况相关。
简单测量3 - Me - His以及β - 丙氨酸或缬氨酸可提高对不良事件的预测能力，表明血浆氨基酸谱分析在住院心力衰竭患者风险分层中具有实用性。
The clinical outcome of heart failure (HF) is complicated by the presence of multiple comorbidities including malnutrition and cachexia, and prediction of the outcome is still difficult in each patient. Metabolomics including amino acid profiling enables detection of alterations in whole body metabolism. The aim of this study was to determine whether plasma amino acid profiling improves prediction of clinical outcomes in patients with HF. We retrospectively examined 301 HF patients (70 ± 15 years old; 59% male). Blood samples for measurements of amino acid concentrations were collected in a fasting state after stabilization of HF. Plasma amino acid concentrations were measured using ultraperformance liquid chromatography. Clinical endpoint of this study was adverse event defined as all‐cause death and unscheduled readmission due to worsening HF or lethal arrhythmia. During a mean follow‐up period of 380 ± 214 days, 40 patients (13%) had adverse events. Results of analyses of variable importance in projection score, a measure of a variable's importance in partial least squares–discriminant analysis (PLS‐DA) showed that the top five amino acids being associated with adverse events were 3‐methylhistidine (3‐Me‐His), β‐alanine, valine, hydroxyproline, and tryptophan. Multivariate Cox‐proportional hazard analyses indicated that a high 3‐Me‐His concentration and low β‐alanine and valine concentrations were independently associated with adverse events. When HF patients were divided according to the cut‐off values of amino acids calculated from receiver operating characteristic curves, Kaplan–Meier survival curves showed that event‐free survival rates were lower in HF patients with high 3‐Me‐His than in HF patients with low 3‐Me‐His (68% vs. 91%, P < 0.01). In a subgroup with high 3‐Me‐His, HF patients with low β‐alanine and those with low valine had significantly lower event‐free survival rates than did HF patients with high β‐alanine and those with high valine, respectively. On the other hand, Kaplan–Meier curves of event‐free survival rates did not differ between HF patients with and those without low β‐alanine and low valine in subgroups of patients with low 3‐Me‐His. Inclusion of both high 3‐Me‐His and low β‐alanine or low valine into the adjustment model including N‐terminal pro‐brain natriuretic peptide improved the accuracy of prediction of adverse events after discharge. 3‐Me‐His concentration was associated with muscle mass and nutritional status. Simple measurement of 3‐Me‐His with either β‐alanine or valine improved the predictive ability for adverse events, indicating the utility of plasma amino acid profiling in risk stratification of hospitalized HF patients.
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影响因子：
4.1
作者：
Ohori K;Yano T;Katano S;Kouzu H;Honma S;Shimomura K;Inoue T;Takamura Y;Nagaoka R;Koyama M;Nagano N;Fujito T;Nishikawa R;Ishigo T;Watanabe A;Hashimoto A;Miura T
通讯作者：
Miura T
影响因子：
24
作者：
Cheng, Mei-Ling;Wang, Chao-Hung;Yang, Ning-I
通讯作者：
Yang, Ning-I
DOI：
10.1111/j.1365-2362.1988.tb01282.x
发表时间：
1988-12-01
影响因子：
5.5
作者：
MORRISON, WL;GIBSON, JNA;RENNIE, MJ
通讯作者：
RENNIE, MJ
影响因子：
18.2
作者：
Manzano, Luis;Babalis, Daphne;Flather, Marcus D.
通讯作者：
Flather, Marcus D.
影响因子：
5.9
作者：
Aquilani R;La Rovere MT;Corbellini D;Pasini E;Verri M;Barbieri A;Condino AM;Boschi F
通讯作者：
Boschi F