琥珀酸将心房功能障碍与心源性栓塞性卒中联系起来。
Succinate links atrial dysfunction and cardioembolic stroke.
机构信息
From the Departments of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins Hospital, Baltimore, MD; Center for Genomic Medicine (Z.A., Z.W., W.T.K.) and Division of Neurocritical Care and Emergency Neurology, Department of Neurology (Z.A., Z.W., W.T.K.), Massachusetts General Hospital, Harvard Medical School; and Division of Cardiovascular Medicine (R.E.G.), Beth Israel Deaconess Hospital, Boston, MA.
出版信息
Neurology. 2019 Feb 19;92(8):e802-e810. doi: 10.1212/WNL.0000000000006957. Epub 2019 Jan 23.
OBJECTIVE
To determine whether altered metabolic profiles represent a link between atrial dysfunction and cardioembolic (CE) stroke, and thus whether underlying dysfunctional atrial substrate may contribute to thromboembolism risk in CE stroke.
METHODS
A total of 144 metabolites were measured using liquid chromatography-tandem mass spectrometry in plasma samples collected within 9 hours of stroke onset in 367 acute stroke patients. Stroke subtype was assigned using the Causative Classification of Stroke System, and CE stroke (n = 181) was compared to non-CE stroke (n = 186). Markers of left atrial dysfunction included abnormal atrial function (P-wave terminal force in lead V1, PTFV >4,000 μV·ms), left atrial enlargement on echocardiography, and frank atrial fibrillation on ECG. Stroke recurrence risk was assessed using CHADS and CHADS-VASc scores. Associations between metabolites and CE stroke, atrial dysfunction, and stroke recurrence risk were evaluated using logistic regression models.
RESULTS
Three tricarboxylic acid metabolites-succinate (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.36-2.15, = 1.37 × 10), α-ketoglutarate (OR 1.62, 95% CI 1.29-2.04, = 1.62 × 10), and malate (OR 1.58, 95% CI 1.26-1.97, = 2.57 × 10)-were associated with CE stroke. Succinate (OR 1.36, 95% CI 1.31-1.98, = 1.22 × 10), α-ketoglutarate (OR 2.14, 95% CI 1.60-2.87, = 2.08 × 10), and malate (OR 2.02, 95% CI 1.53-2.66, = 1.60 × 10) were among metabolites also associated with subclinical atrial dysfunction. Of these, succinate was also associated with left atrial enlargement (OR 1.54, 95% CI 1.23-1.94, = 1.06 × 10) and stroke recurrence based on dichotomized CHADS (OR 2.63, 95% CI 1.68-4.13, = 3.00 × 10) and CHADS-VASc (OR 2.43, 95% CI 1.60-3.68, = 4.25 × 10) scores.
CONCLUSIONS
Metabolite profiling identified changes in succinate associated with CE stroke, atrial dysfunction, and stroke recurrence, revealing a putative underlying link between CE stroke and energy metabolism.
目的
确定代谢谱的改变是否代表了心房功能障碍与心源性栓塞性（CE）卒中之间的联系，以及潜在的功能障碍性心房基质是否可能导致 CE 卒中的血栓栓塞风险增加。
方法
在 367 例急性卒中患者发病后 9 小时内采集的血浆样本中，使用液相色谱-串联质谱法测量了 144 种代谢物。使用卒中病因分类系统（Causative Classification of Stroke System）确定卒中亚型，将 CE 卒中（n=181）与非 CE 卒中（n=186）进行比较。左心房功能障碍的标志物包括异常的心房功能（V1 导联 P 波终末电势，PTFV＞4000 μV·ms）、超声心动图上的左心房扩大和心电图上的阵发房颤。使用 CHADS 和 CHADS-VASc 评分评估卒中复发风险。使用逻辑回归模型评估代谢物与 CE 卒中、心房功能障碍和卒中复发风险之间的相关性。
结果
三种三羧酸代谢物琥珀酸（OR 1.71，95%置信区间 [CI] 1.36-2.15， = 1.37×10）、α-酮戊二酸（OR 1.62，95% CI 1.29-2.04， = 1.62×10）和苹果酸（OR 1.58，95% CI 1.26-1.97， = 2.57×10）与 CE 卒中相关。琥珀酸（OR 1.36，95% CI 1.31-1.98， = 1.22×10）、α-酮戊二酸（OR 2.14，95% CI 1.60-2.87， = 2.08×10）和苹果酸（OR 2.02，95% CI 1.53-2.66， = 1.60×10）也是与亚临床心房功能障碍相关的代谢物之一。其中，琥珀酸还与左心房扩大（OR 1.54，95% CI 1.23-1.94， = 1.06×10）和基于二分法 CHADS（OR 2.63，95% CI 1.68-4.13， = 3.00×10）和 CHADS-VASc（OR 2.43，95% CI 1.60-3.68， = 4.25×10）评分的卒中复发相关。
结论
代谢物谱分析确定了琥珀酸与 CE 卒中、心房功能障碍和卒中复发之间的变化，揭示了 CE 卒中与能量代谢之间潜在的联系。
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